Grade Heterogeneity in High-Grade Urothelial Carcinomas: Does It Have an Impact on the Survival of Patients With Intermediate/High-Risk Nonmuscle-Invasive Bladder Cancer Who Received Adequate Adjuvant Bacillus Calmette-Guérin Therapy?

PURPOSE: We aimed to compare recurrence-free survival (RFS) and progression-free survival (PFS) of the patients with pure high-grade (HG) vs mixed-grade (MG) nonmuscle-invasive bladder cancer who received adequate bacillus Calmette-Guérin therapy. MATERIALS AND METHODS: We conducted a retrospective cohort analysis using data from an institutional database. The study included patients diagnosed with HG nonmuscle-invasive bladder cancer at the initial transurethral resection specimen between 2010 and 2020. The initial transurethral resection specimens of all patients were reevaluated by a dedicated uropathologist. The percentage of low-grade tumor areas accompanying HG areas was determined for each case. Time-to-event analysis was performed using the Kaplan-Meier method. RFS and PFS rates were compared between groups. RESULTS: Of the 203 patients enrolled in the study, 69 (34%) had MG tumors. Recurrence was observed in 41 out of 134 patients (30.6%) in the HG group and in 19 out of 69 patients (27.5%) in the MG group. The 36-month RFS rates were 69% (CI: 62-77) and 72% (CI: 62-83) for the HG-urothelial carcinoma (UC) and MG-UC groups, respectively. The RFS rates were similar between groups (log-rank, P = .58). Progression was observed in 22 out of 134 patients (16.4%) in the HG group and in 4 out of 69 patients (5.8%) in the MG group. The 36-month PFS rates were 84% (CI: 77-90) and 94% (CI: 89-100) for the HG-UC and MG-UC groups, respectively. The pure HG-UC group had a worse PFS than the MG-UC group (log-rank, P = .042). Multivariate analysis demonstrated that age and tumor grade were significant risk factors for the development of progression. CONCLUSIONS: The indication of MG-UC category separately from pure HG carcinomas in the pathology report seems to be an important issue that can guide patient management. In this way, both more accurate risk classification and more accurate patient counseling can be performed. More importantly, the treatment plan can be made more accurately. For more precise conclusions, our results should be supported by prospective studies with larger sample size.

Testicular sperm retrieval for intracytoplasmic sperm injection: when to consider it after unsuccessful intracytoplasmic sperm injection with ejaculated sperm?

BACKGROUND: The question of whether patients are more likely to succeed with testicular sperm intracytoplasmic sperm injection (T-ICSI) after unsuccessful ICSI with ejaculated sperm (Ej-ICSI) remains unknown. OBJECTIVE: The study aimed to identify potential predictors of successful T-ICSI in men with idiopathic infertility and oligozoospermia (sperm concentration < 15 × 106/mL, non-azoospermic) who had previously experienced unsuccessful Ej-ICSI. MATERIALS AND METHODS: In total, 154 couples with male partners who had oligozoospermic conditions after two unsuccessful cycles of Ej-ICSI switched to T-ICSI. Before initiating T-ICSI, the sperm DNA fragmentation index (DFI) was assessed in ejaculated specimens. Participants were divided into two groups: group A (live birth (+), n = 60) and group B (live birth (-), n = 94). RESULTS: Fertilization, clinical pregnancy, live births, and miscarriages had rates of 72.7%, 44.2%, 39%, and 5.2%, respectively. The total motile sperm (TMS) count in group A was significantly higher (3.8 ± 1.5 million) than in group B (3 ± 1.6 million; p = 0.002). DFI was significantly higher in group A (24.2 ± 12.3) than in group B (18.1 ± 11; p = 0.001). Hormone levels and oocyte counts showed no statistically significant differences between groups. Multivariate regression analysis revealed that TMS (odds ratio [OR]: 1.46; 95% CI, 1.14-1.87, p = 0.003) and DFI (OR: 1.04; 95% CI, 1.01-1.08, p = 0.009) were found to be significant predictors of live birth outcomes. At a cutoff point of 2.55 (area under the curve [AUC] = 0.65), the optimal sensitivity and specificity values for TMS were 78% and 48%, respectively. At a cutoff point of 25.8 (AUC = 0.65), DFI had a maximum sensitivity of 51.7% and a specificity of 78.7%. CONCLUSIONS: TMS and DFI were found to be significant predictors of live birth outcomes in couples with oligozoospermic male partners undergoing T-ICSI. These findings may help clinicians tailor treatment strategies for this specific patient population.

Anatomic outcomes of sacrohysteropexy without posterior mesh placement in patients with asymptomatic grade 1 and 2 rectoceles: Is a rectouterine mesh really necessary?

OBJECTIVES: To present the anatomic outcomes of sacrohysteropexy surgery without posterior mesh placement in patients with asymptomatic grade 1 and 2 rectoceles. METHODS: The patients who underwent abdominal sacrohysteropexy without posterior mesh placement for the treatment of symptomatic grade 3 and 4 anterior/apical prolapse + asymptomatic grade 1 and 2 rectocele between May 2015 and January 2021 were evaluated retrospectively. The success rate, the anatomic outcomes (for anterior, apical, and posterior pelvic organ prolapse [POP]), and perioperative data of the surgical procedure were assessed. The objective failure criteria after surgery included the presence of grade 1 or higher in any compartment (anatomical criteria), recurrent POP requiring an operation, and/or usage of pessaries. Perioperative adverse events were categorized according to the Clavien-Dindo classification. RESULTS: Fifty-one patients underwent sacrohysteropexy without posterior mesh. The mean age of the patients was 56.8 ± 10 years. The success rates (anatomical outcomes) for the anterior/apical and posterior POP in the study group were 60.7%, 54.9%, and 58.8%, respectively, at a median follow-up time of 40.24 (24-71) months. The median hospital stay was 3.1 (2-6) days. The mean estimated blood loss was 127.6 (80-150) mL. The mean operation time was 114 (90-156) min. The mean urethral and catheter removal times were 1.3 (1, 2) and 2.1 (2-4) days, respectively. The mean recovery time of gastrointestinal motility was 14.4 h (11-35). CONCLUSIONS: Sacrohysteropexy without posterior mesh placement might be associated with less pain, shorter operative time, and shorter recovery time of gastrointestinal motility, without compromising the anatomic success.

Candida khanbhai sp. nov., a new clinically relevant yeast within the Candida haemulonii species complex.

Invasive fungal infections caused by non-albicans Candida species are increasingly reported. Recent advances in diagnostic and molecular tools enabled better identification and detection of emerging pathogenic yeasts. The Candida haemulonii species complex accommodates several rare and recently described pathogenic species, C. duobushaemulonii, C. pseudohaemulonii, C. vulturna, and the most notorious example is the outbreak-causing multi-drug resistant member C. auris. Here, we describe a new clinically relevant yeast isolated from geographically distinct regions, representing the proposed novel species C. khanbhai, a member of the C. haemulonii species complex. Moreover, several members of the C. haemulonii species complex were observed to be invalidly described, including the clinically relevant species C. auris and C. vulturna. Hence, the opportunity was taken to correct this here, formally validating the names of C. auris, C. chanthaburiensis, C. konsanensis, C. metrosideri, C. ohialehuae, and C. vulturna.

Although C. albicans remains the major pathogenic yeast, other previously rare or even novel species are on the rise in the clinic. The most notorious example is the rapid global emergence of multidrug-resistant C. auris. Here we describe its novel sibling species C. khanbhai.

Comparison of retrograde ureterorenoscopy (URS) and percutaneous anterograde ureteroscopy for removal of impacted upper ureteral stones >10mm in the elderly population

ABSTRACT Purpose: We aimed to compare the success and complication rates of the anterograde and retrograde Ureterorenoscopy (URS) for impacted upper ureteral stones in patients > 65 years of age. Materials and Methods: Data of 146 patients >65 years of age and underwent anterograde URS (n=68) in supine position or retrograde URS (n=78) for upper ureteral impacted stones>10 mm between January 2014 and September 2018 were collected prospectively. The groups were compared for success and complication rates, duration of operation, hospital stay, and ancillary procedures. Results: Anterograde and retrograde URS groups were similar for demographic and stone related characteristics. The success rate of the anterograde URS group was significantly higher than the retrograde URS group (97.1% vs. 78.2%, p=0.0007). The complication rates were similar for the two groups (p=0.86). Clavien grade I and II complications were observed in 3 patients in each group. The mean hemoglobin drop was 0.5 g/dL in the anterograde URS group and blood transfusion was not performed in any of the patients. The mean duration of operation was 41.2±12.5 minutes in the mini-PNL group and 59.6±15.1 minutes in the RIRS group and the difference was statistically significant (p=0.02). The median duration of hospitalization was 1 day for both groups. Conclusions: Performing anterograde URS in supine position provided better success rates and similar complication rates compared to retrograde URS. Based on these results anterograde URS shall be considered as one of the primary treatment options for management of impacted upper ureteral stones in the elderly population.

Comparison of retrograde ureterorenoscopy (URS) and percutaneous anterograde ureteroscopy for removal of impacted upper ureteral stones >10mm in the elderly population.

PURPOSE: We aimed to compare the success and complication rates of the anterograde and retrograde Ureterorenoscopy (URS) for impacted upper ureteral stones in patients > 65 years of age. MATERIALS AND METHODS: Data of 146 patients >65 years of age and underwent anterograde URS (n=68) in supine position or retrograde URS (n=78) for upper ureteral impacted stones>10 mm between January 2014 and September 2018 were collected prospectively. The groups were compared for success and complication rates, duration of operation, hospital stay, and ancillary procedures. RESULTS: Anterograde and retrograde URS groups were similar for demographic and stone related characteristics. The success rate of the anterograde URS group was significantly higher than the retrograde URS group (97.1% vs. 78.2%, p=0.0007). The complication rates were similar for the two groups (p=0.86). Clavien grade I and II complications were observed in 3 patients in each group. The mean hemoglobin drop was 0.5 g/dL in the anterograde URS group and blood transfusion was not performed in any of the patients. The mean duration of operation was 41.2±12.5 minutes in the mini-PNL group and 59.6±15.1 minutes in the RIRS group and the difference was statistically significant (p=0.02). The median duration of hospitalization was 1 day for both groups. CONCLUSIONS: Performing anterograde URS in supine position provided better success rates and similar complication rates compared to retrograde URS. Based on these results anterograde URS shall be considered as one of the primary treatment options for management of impacted upper ureteral stones in the elderly population.

Reliability and validity of Turkish versions of the interstitial cystitis symptom index and interstitial cystitis problem index.

AIM: To validate the Turkish versions of the interstitial cystitis symptom index (ICSI) and interstitial cystitis problem index (ICPI) for use in Turkish speaking patients with bladder pain syndrome/interstitial cystitis (BPS/IC). METHODS: After translation of the original ICSI and ICPI into the Turkish language, Turkish versions of ICSI and ICPI were self-administered to all participants. Test-retest reliability (intraclass correlation coefficient) was evaluated at 2 weeks intervals in the BPS/IC group. Internal consistency was evaluated using Cronbach's alpha. Scores of ICSI and ICPI was compared between BPS/IC and control groups to examine discriminant validity. Criterion validity was examined via investigating the correlations between bladder diary data (24-hour frequency and nocturia), visual analogue scale (VAS) scores, and results to the corresponding questions in ICSI and ICPI. RESULTS: Results of 79 patients with BPS/IC and 50 control patients were analyzed. Both indices showed high internal consistency (Cronbach's α for ICSI and ICPI was 0.879 and 0.923, respectively). The test-retest reliability of ICSI and ICPI was high for total scores and subdomains of both indices (intraclass correlation coefficient was 0.722 for ICSI and 0.777 for ICPI). Scores of both indices were significantly higher in BPS/IC group than the control group (P < .001). Statistically significant correlations were found between 24-hour frequency, nocturia, VAS scores, and corresponding questions in the indices. A statistically significant and strong correlation was observed between ICSI and ICPI scores (P < .001, rS = .632). CONCLUSION: Turkish versions of ICSI and ICPI are reliable, consistent, and valid instruments to evaluate symptoms of Turkish speaking patients with BPS/IC.

Increasing Trends of Reduced Susceptibility to Antifungal Drugs Among Clinical Candida glabrata Isolates in Kuwait.

Among non-albicans Candida species, Candida glabrata is the leading cause of invasive infections in critically ill patients. It is intrinsically less susceptible to fluconazole/other azoles that limits therapeutic options. This study determined distribution of C. glabrata in clinical specimens and determined their susceptibility to fluconazole, caspofungin, and amphotericin B by E test. During 8-year period (2011-2018), 1,410 isolates were obtained from 1,410 patients including 600, 409, and 131 isolates from respiratory, urine, and bloodstream specimens, respectively. Proportion of C. glabrata isolates was nearly the same during the two 4-year periods. Demographic details were available from 731 patients and susceptibility data for 1,225 isolates. C. glabrata isolation from bloodstream, respiratory, and urine specimens was higher from elderly (>60 years) versus younger patients. More bloodstream and urine isolates were obtained from female patients, however, more respiratory isolates were recovered from male patients (p = <0.05). Resistance to all three drugs increased during 2015-2018 compared with 2011-2014 but was more pronounced for fluconazole (p = 0.001). More isolates with reduced susceptibility to fluconazole/amphotericin B were obtained from elderly patients versus younger subjects and urine versus respiratory samples (p = <0.05). Our data show increasing trends of reduced susceptibility to antifungals, particularly fluconazole, among clinical C. glabrata isolates in Kuwait. Most isolates with reduced susceptibility to fluconazole/amphotericin B were obtained from elderly patients and urine/respiratory samples with urinary tract appearing as the most favorable niche for antifungal drug resistance development. The study also highlights the need for continued surveillance and better antifungal drug stewardship to control resistance development in C. glabrata.

Changing trends in epidemiology and antifungal susceptibility patterns of six bloodstream Candida species isolates over a 12-year period in Kuwait.

Changing trends in incidence and antifungal susceptibility patterns of six Candida species causing candidemia in Kuwait between 2006-2017 are reported. A total of 2075 isolates obtained from 1448 patients were analyzed. Identity of Candida species isolates was determined by phenotypic methods and confirmed by PCR amplification/PCR-sequencing of rDNA and/or MALDI-TOF MS. Antifungal susceptibility was determined by Etest. C. albicans accounted for 539 (37.22%) cases followed by C. parapsilosis (n = 502, 34.67%), C. tropicalis (n = 210, 14.5%), C. glabrata (n = 148, 10.22%), C. krusei (n = 27, 1.81%) and C. dubliniensis (n = 22, 1.5%). The comparative percent distribution of Candida species causing candidemia between 2006-2011 and 2012-2017 was as follows: C. albicans 41.8% and 33.1%, C. parapsilosis complex 32.01% and 37.04%, C. tropicalis 13.59% and 15.31%, and C. glabrata 8.77% and 11.51%, C. krusei 2.0% and 1.7%, and C. dubliniensis 1.75 and 1.3%, respectively. Three of 371 C. albicans isolates during 2006-2011 and five of 363 during 2012-2017 were resistant to fluconazole. Among C. parapsilosis isolates, one of 310 during 2006-2011 and 21 of 446 during 2012-2017 were resistant to this drug. Furthermore, at an epidemiologic cutoff value (ECV) of ≤0.5 µg/ml, 70.1% C. albicans isolates were wild-type for fluconazole during 2006-2011 as compared to 58.1% during 2012-2017. Likewise, at an ECV of ≤2 µg/ml, 98.0% of C. parapsilosis isolates were wild-type during 2006-2011 as compared to 93.4% during 2012-2017. Clonal spread of fluconazole-resistant C. parapsilosis in one major hospital was documented. An 8.8% shift in favor of non-albicans Candida species with concomitant increase in MICs between the two periods preludes emergence of fluconazole-resistant candidemia cases in Kuwait.

Invasive Candida auris infections in Kuwait hospitals: epidemiology, antifungal treatment and outcome.

PURPOSE: Candida auris is a recently recognized yeast pathogen, which has attracted worldwide attention due to its multidrug-resistant nature and associated high mortality rates. Its persistence in hospital environment and propensity of nosocomial transmission underscores the need of continuous monitoring to prevent outbreaks. Since the first case of C. auris candidemia in May, 2014, we have identified 17 additional invasive cases, which are described here. METHODS: Identity of 17 isolates originating from proven or possible cases of invasive C. auris infection and identified as Candida haemulonii by Vitek 2 yeast identification system was confirmed by PCR-sequencing of rDNA. Information about risk factors, treatment and outcomes were retrospectively retrieved from case files. Antifungal susceptibility testing was performed by Etest. RESULTS: Thirteen cases of candidemia and 4 cases of other invasive infections were detected in 6 hospitals across Kuwait. Major risk factors included adult patients with cancer, diabetes, gastrointestinal/liver diseases and extended (> 25 days) hospital stay. All isolates were resistant to fluconazole. Additionally, 5 and 4 isolates were also resistant to voriconazole and amphotericin B, respectively. Despite antifungal treatment, 9 of 15 patients died. Most patients (n = 12) were hospitalized in 2 hospitals that are in close proximity, whereas 5 other patients were from 3 hospitals that are situated > 10 km apart. CONCLUSIONS: Occurrence of successive cases of invasive C. auris infections with resulting mortality in nine patients suggests persistence of this multidrug-resistant yeast in major hospitals in Kuwait. Early detection by continuous surveillance and enforcement of infection control measures are recommended.

Population structure and molecular genetic characterization of clinical Candida tropicalis isolates from a tertiary-care hospital in Kuwait reveal infections with unique strains.

Candida tropicalis is a frequently isolated yeast species causing bloodstream, urinary tract and other infections particularly in patients admitted to intensive care units (ICUs) and those requiring prolonged urinary catheterization (UC) or receiving broad-spectrum antibiotics (BSA). This study investigated clinical characteristics and genetic relatedness among C. tropicalis strains isolated from patients at Al-Amiri Hospital in Kuwait. C. tropicalis strains (n = 63) isolated from blood, genito-urinary, respiratory (RT) and digestive (GIT) tracts and wound sites from 54 patients were used. All isolates were phenotypically identified and tested against six antifungal drugs by using Vitek 2 system. Molecular identification was performed by PCR amplification of rDNA. Fingerprinting was achieved by 6-loci-based multilocus sequence typing (MLST) and data were analyzed by BioNumerics software for phylogenetic relationships. Patients mean age was >65 years and >20% patients were hospitalized in ICUs. Most patients had underlying conditions that included UC, BSA, diabetes and RT/GIT abnormalities. Most candiduria cases had UC, ureteric stent or suprapubic catheters. All isolates were identified as C. tropicalis by Vitek 2 and by species-specific PCR. Sixty-two isolates were susceptible to all tested antifungal drugs. MLST identified 59 diploid sequence types (DSTs) including 54 newly-identified DSTs. C. tropicalis isolates from multiple sites of same patient usually belonged to different DSTs. Interestingly, 56 of 57 isolates from 48 patients belonged to unique genotypes. Only six isolates from six patients belonged to three DSTs (clusters), however, C. tropicalis strains in each cluster were isolated >3 months apart. Our data show diverse origins of C. tropicalis infections in Kuwait as most isolates were unique strains. There was no obvious correlation between cluster isolates with time of isolation and/or hospital ward of their origin. This study presents the first MLST analysis of C. tropicalis isolates from Middle East and may be useful for studying genetic relationships among global C. tropicalis strains.

Diversity of multi-drug resistant Acinetobacter baumannii population in a major hospital in Kuwait.

Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious health care associated complications in critically ill patients. In the current study we report on the diversity of the clinical multi-drug resistant (MDR) A. baumannii in Kuwait by molecular characterization. One hundred A. baumannii were isolated from one of the largest governmental hospitals in Kuwait. Following the identification of the isolates by molecular methods, the amplified bla OXA-51-like gene product of one isolate (KO-12) recovered from blood showed the insertion of the ISAba19 at position 379 in bla OXA-78. Of the 33 MDR isolates, 28 (85%) contained bla OXA-23, 2 (6%) bla OXA-24 and 6 (18%) bla PER-1 gene. We did not detect bla OXA-58, bla VIM, bla IMP, bla GES, bla VEB, and bla NDM genes in any of the tested isolates. In three bla PER-1 positive isolates the genetic environment of bla PER-1 consisted of two copies of ISPa12 (tnpiA1) surrounding the bla PER-1 gene on a highly stable plasmid of ca. 140-kb. Multilocus-sequence typing (MLST) analysis of the 33 A. baumannii isolates identified 20 different STs, of which six (ST-607, ST-608, ST-609, ST-610, ST-611, and ST-612) were novel. Emerging STs such as ST15 (identified for the first time in the Middle East), ST78 and ST25 were also detected. The predominant clonal complex was CC2. Pulsed-field gel electrophoresis and MLST defined the MDR isolates as multi-clonal with diverse lineages. Our results lead us to believe that A. baumannii is diverse in clonal origins and/or is undergoing clonal expansion continuously while multiple lineages of MDR A. baumannii circulate in hospital ward simultaneously.

Isolation of Salmonella enterica serovar Kentucky strain ST 198 and its H2S-negative variant from a patient: implications for diagnosis.

H2S-producing multiresistant Salmonella enterica serovar Kentucky strain sequence type (ST) 198 and its non-H2S-producing variant were isolated from a patient. Whole-genome comparison showed a base addition in the gene encoding molybdenum cofactor biosynthesis protein C, which could affect H2S production in the variant. Lack of H2S production has implications for diagnosis of salmonella.

Isolation of cholesterol-dependent, multidrug-resistant Candida glabrata strains from blood cultures of a candidemia patient in Kuwait.

BACKGROUND: Candida glabrata has emerged as an important human pathogen associated with systemic and mucosal infections. Here, we describe isolation of two cholesterol-dependent Candida glabrata strains from a candidemia patient which failed to grow on the media devoid of a cholesterol source. METHODS: Both the isolates were recovered from BACTEC Plus Aerobic/F blood culture bottles of a candidemic patient. Since these isolates failed to grow on Sabouraud dextrose agar, Mueller-Hinton agar and RPMI 1640 agar media, their definitive identification required PCR sequencing of the internally transcribed spacer (ITS)1 and ITS2 regions of rDNA and the D1/D2 region sequences within 26S rRNA gene. The cholesterol auxotrophy was determined by their ability to grow on media containing a cholesterol source. The minimum inhibitory concentrations (MICs) to antifungal agents were determined by Etest. RESULTS: The identity of the isolates was confirmed by sequencing of the ITS1 and ITS2 regions of rDNA and the D1/D2 region sequences within 26S rRNA gene and also by matrix-assisted laser desorption and ionization-time-of-flight mass spectrometry with 99.9% confidence value. Both the isolates showed good growth only when media were supplemented with cholesterol, oxbile or blood. Additionally, these isolates were resistant to amphotericin B (MIC ≥32 µg/ml), fluconazole (MIC ≥256 µg/ml), voriconazole (MIC ≥32 µg/ml), itraconazole (MIC ≥32 µg/ml), and posaconazole (MIC ≥32 µg/ml), but susceptible to caspofungin (MIC range 0.064 to 0.19 µg/ml). CONCLUSION: This appears to be the first report on isolation of cholesterol-dependent strains of C. glabrata from a candidemia patient exhibiting resistance to azoles and amphotericin B. Further, the report demonstrates that induction of cholesterol/sterol auxotrophy is associated with resistance to antifungal drugs targeting ergosterol biosynthesis. These observations may have therapeutic implications for the treatment of infections caused by such C. glabrata strains.

Acremonium kiliense: reappraisal of its clinical significance.

A case of Acremonium kiliense peritonitis is described. Diagnosis was established by repeated isolation of the fungus from peritoneal dialysate and by its identification on the basis of morphological characteristics and sequencing of internal transcribed spacer (ITS) regions of ribosomal DNA (rDNA). This report and available literature suggest that A. kiliense may have a greater clinical significance than hitherto recognized.