Currently, the midurethral sling (MUS) is widely used as a standard treatment in patients with stress urinary incontinence (SUI). Several studies have reported the failure rate of MUS to be approximately 5%–20%. In general, sling failure can be defined as persistent SUI after surgery or a temporary improvement in incontinence followed by recurrence. Failure is also often considered to include cases requiring secondary surgery due to mesh exposure, postoperative voiding difficulty, de novo urgency/urge incontinence, and severe postoperative pain. Because of the lack of large-scale, high-quality research on this topic, no clear guidelines exist for second-line management. To date, transurethral bulking agent injections, tape shortening, repeat MUS, pubovaginal sling (PVS) using autologous fascia, and Burch colposuspension are available options for second-line surgery. Repeat MUS is the most widely used second-line surgical method at present. Bulking agent injections have lower durability and efficacy than other treatments. Tape shortening demonstrates a relatively low success rate, but comparable outcomes if the period from first treatment to relapse is short. In patients with intrinsic sphincter deficiency, PVS and retropubic (RP) MUS can be considered first as second-line management because of their higher success rate than other treatments. When revision or reoperation is required due to prior mesh-related complications, PVS or colposuspension, which is performed without a synthetic mesh, is appropriate for second-line surgery. For patients with detrusor underactivity, a readjustable sling can be a better option because of the high risk of postoperative voiding dysfunction in PVS or RP slings.

Currently, the midurethral sling (MUS) is widely used as a standard treatment in patients with stress urinary incontinence (SUI). Several studies have reported the failure rate of MUS to be approximately 5%–20%. In general, sling failure can be defined as persistent SUI after surgery or a temporary improvement in incontinence followed by recurrence. Failure is also often considered to include cases requiring secondary surgery due to mesh exposure, postoperative voiding difficulty, de novo urgency/urge incontinence, and severe postoperative pain. Because of the lack of large-scale, high-quality research on this topic, no clear guidelines exist for second-line management. To date, transurethral bulking agent injections, tape shortening, repeat MUS, pubovaginal sling (PVS) using autologous fascia, and Burch colposuspension are available options for second-line surgery. Repeat MUS is the most widely used second-line surgical method at present. Bulking agent injections have lower durability and efficacy than other treatments. Tape shortening demonstrates a relatively low success rate, but comparable outcomes if the period from first treatment to relapse is short. In patients with intrinsic sphincter deficiency, PVS and retropubic (RP) MUS can be considered first as second-line management because of their higher success rate than other treatments. When revision or reoperation is required due to prior mesh-related complications, PVS or colposuspension, which is performed without a synthetic mesh, is appropriate for second-line surgery. For patients with detrusor underactivity, a readjustable sling can be a better option because of the high risk of postoperative voiding dysfunction in PVS or RP slings.

WD40-repeat (WDR)-containing proteins constitute an evolutionarily conserved large protein family with a broad range of biological functions. In human proteome, WDR makes up one of the most abundant protein-protein interaction domains. Members of the WDR protein family play important roles in nearly all major cellular signalling pathways. Mutations of WDR proteins have been associated with various human pathologies including neurological disorders, cancer, obesity, ciliopathies and endocrine disorders. This review provides an updated overview of the biological functions of WDR proteins and their mutations found in congenital disorders. We also highlight the significant role of WDR proteins in ciliopathies and endocrine disorders. The new insights may help develop therapeutic approaches targeting WDR motifs.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are particularly prevalent in women. Recurrent UTIs significantly diminish quality of life due to their symptoms and frequent relapses. Patients often experience immediate relapse following slightly strenuous activities or intense psychological stress. In this review, we explore why infections persist despite the advent of various treatments and suggest strategies to manage recurrent cystitis by targeting the mechanisms of adhesion and infection. Vitamin D levels and the expression of neutrophil gelatinase-associated lipocalin are linked to the recurrence of UTIs. During a UTI, bacteria employ adhesins to invade the urinary tract, adhere to urothelial cells, and then penetrate these cells, where they rapidly multiply to establish intracellular bacterial communities. Bacteria can also form quiescent intracellular reservoirs that escape immune responses and antibiotic treatments, leading to recurrence under certain conditions. The surface proteins of bacteria and D-mannose are crucial in the adhesion of bacteria to the urothelium. Understanding these processes provides valuable insights into potential therapeutic approaches that focus on preventing bacterial attachment and cluster formation. By disrupting the ability of bacteria to adhere to and form clusters on cells, we can better manage recurrent UTIs and improve patient outcomes.

Background and Objectives: Middle ear implants (MEI) have been reported to be an effective and safe alternative for the treatment of sensorineural hearing loss (SNHL) and conductive hearing loss (CHL). This study aimed to compare the functional outcomes between SNHL and CHL in terms of audiological gains.Subjects and Method The medical records of 14 consecutive SNHL and CHL patients who underwent MEI surgeries from 2015 to 2019 by a single surgeon were retrospectively reviewed. Audiological changes using hearing aids (HA) and MEI were compared. Results: In SNHL, the mean unaided air-conduction pure tone audiometry (PTA), (57.7 dB HL) decreased significantly using HA and MEI (44.7 and 41.4 dB HL), but with no significant difference from each other. Unaided word recognition score (WRS) at 65 dB HL (45.1%) was significantly improved using HA and MEI (72.6% and 76.6%), with no significant difference. In CHL, the mean unaided air-conduction and bone-conduction PTA were 77.1 (57.5-93.8) and 44.1 (26.3-57.5) dB HL. Three patients could not use conventional HAs due to otorrhea and deformity of the external auditory canal by previous surgeries and 4 patients had used conventional HAs before MEI. Though both HA and vibrant soundbridge (VSB) showed improvement of hearing thresholds (32.0 and 48.8 dB HL) and WRS (80.0% and 94.9%), it was significant only when using VSB. There was no significant difference between HA and VSB. Conclusion MEI can be an effective treatment option for both SNHL and CHL patients, especially for those who suffered from problems using conventional HA.

OBJECTIVE: Since 2018, the surviving sepsis campaign recommended one-hour bundle therapy in septic shock patients. On the other hand, evidence for the effectiveness of bundle therapy has not been established. The object of this study was to determine the prognostic value of one-hour bundle completion in septic shock patients. METHODS: This prospectively collected registry-based, retrospective observational study, between January 2016 and December 2018. A one-hour bundle in septic shock was defined by the serum lactate measurements, blood cultures, administration of antibiotics, and adequate fluid administration within one hour from emergency department admission. Eligible septic shock patients were included in the analysis, and the prognostic abilities of the completion of the one-hour bundle and each item were analyzed. The primary outcome was the 28-day mortality. RESULTS: The study included 381 patients, and the overall 28-day mortality was 24.7%. The overall one-hour bundle completion rate was 11.3%, and each completion rate of serum lactate measurement, blood cultures, administration of antibiotics, and adequate fluid administration were 85.8%, 74.3%, 19.4%, and 48.6%, respectively. On the other hand, overall bundle completion as well as each bundle were not associated with the 28-day mortality except for adequate fluid administration (odds ratio [OR], 0.67 [95% confidence interval (CI), 0.30–1.50]; OR, 1.33 [95% CI, 0.66–2.70]; OR, 1.50 [95% CI 0.85–2.64]; OR, 1.17 [95% CI 0.66–2.07]; and OR, 0.54 [95% CI, 0.34–0.87], respectively). Multivariate logistic regression analysis showed that adequate fluid administration was independently associated with the 28-day mortality (OR, 0.22 [95% CI, 0.09–0.55]; P=0.001). CONCLUSION In this study, most of the one-hour bundle completions were not associated with 28-day mortality. Although adequate fluid administration was associated with the 28-day mortality, multicenter interventional study will be needed to generalize this result.

PURPOSE: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC. MATERIALS AND METHODS: We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULT: We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding. CONCLUSION: This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.
Bevacizumab ; Carcinoma, Renal Cell ; Diagnosis ; Disease-Free Survival ; Erlotinib Hydrochloride ; Fumarate Hydratase ; Germ-Line Mutation ; Hemorrhage ; Humans ; Leiomyomatosis ; Retrospective Studies

Bullous pemphigoid (BP) is a chronic and recurrent bullous disorder that may be associated with the administration of certain drugs. Recently, bullous cutaneous adverse events after immunotherapy (IT) or targeted therapy have been increasingly reported. Here, we report a case of BP in a patient diagnosed with metastatic melanoma after treatment with pembrolizumab, dabrafenib, and trametinib. Histopathological examination showed a subepidermal blister with perivascular lymphocytic and eosinophilic infiltration; the accompanying findings of linear immunoglobulin G and C3 deposition by immunofluorescence microscopy were consistent with BP. Since IT agents may initiate immune dysregulation and pathologic autoantibody production, which are required for the pathogenesis of BP, the lesions were thought to be cutaneous adverse events caused by IT.

Background: There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. Materials and Methods: We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. Results: Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0). Conclusion The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR

Background: There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. Materials and Methods: We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. Results: Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0). Conclusion The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR