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How cells respond to DNA damage is key to maintaining genome integrity or facilitating genetic change. In fungi, DNA damage responses have been extensively characterized in the model budding yeast Saccharomyces cerevisiae, which is generally not pathogenic. However, it is not clear how closely these responses resemble those in fungal pathogens, in which genetic change plays an important role in the evolutionary arms race between pathogen and host and the evolution of antifungal drug resistance. A close relative of S. cerevisiae, Candida glabrata, is an opportunistic pathogen that displays high variability in chromosome structure among clinical isolates and rapidly evolves antifungal drug resistance. The mechanisms facilitating such genomic flexibility and evolvability in this organism are unknown. Recently we characterized the DNA damage response of C. glabrata and identified several features that distinguish it from the well characterized DNA damage response of S. cerevisiae. First, we discovered that, in contrast to the established paradigm, C. glabrata effector kinase Rad53 is not hyperphosphorylated upon DNA damage. We also uncovered evidence of an attenuated DNA damage checkpoint response, wherein in the presence of DNA damage C. ROCK inhibitor glabrata cells did not accumulate in S-phase and proceeded with cell division, leading to aberrant mitoses and cell death. Finally, we identified evidence of transcriptional rewiring of the DNA damage response of C. glabrata relative to S. cerevisiae, including an upregulation of genes involved in mating and meiosis-processes that have not been reported in C. glabrata. Together, these results open new possibilities and raise tantalizing questions of how this major fungal pathogen facilitates genetic change.

The standard treatment for patients with clinical T1bN0M0 esophageal squamous cell carcinoma is radical esophagectomy. Definitive chemoradiotherapy is regarded as a treatment option, and recently, good clinical outcomes of this treatment have been reported. This study compared prognosis after definitive chemoradiotherapy with radical esophagectomy.

From January 2011 to December 2019, 68 consecutive patients who were diagnosed clinical T1bN0M0 squamous cell carcinoma were enrolled and investigated retrospectively. Patients were classified into two groups whether treated by surgery or definitive chemoradiotherapy. Survival outcomes were compared, and subsequent therapies after recurrence were also investigated.

Among 68 patients, 39 patients underwent surgery and 29 patients received definitive chemoradiotherapy. No significant difference was noted in overall survival between the two groups. However, the rate of 5-year recurrence-free survival was significantly lower in definitive chemoradiotherapy group trol disease within local recurrence, and salvage therapy for local lesions could contribute to long-term survival.

Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to-discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results.

Prospective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were the standard of care.

Fast-Tracking of Liver Transplant patients is feasible and can be applied as the standard of care.

Interstitial cystitis/bladder pain syndrome (IC/BPS) and irritable bowel syndrome (IBS) often occur concomitantly without an obvious reason. It is important to determine the relationship between these related diseases. We aimed to determine whether IBS increase the risk of IC/BPS.

We identified newly diagnosed IBS patients between 2002 and 2013 from a nationwide database as the IBS cohort. Subjects diagnosed with IC/BPS before IBS were excluded. Cox's regression analysis with a hazard ratio (HR) of IC/BPS between IBS and the non-IBS cohort was applied to unmatched and matched (16 confounders of propensity scores) models. The time from diagnosis of IBS to IC/BPS was also calculated.

In the unmatched group, which included 100,124 IBS (55% female) and 874,048 non-IBS patients, the IC/BPS adjusted HR was 1.292 (95% confidence interval [CI], 1.131-1.476;p < 0.0001) in the IBS cohort compared with the non-IBS cohort. In the matched group, there were 85,359 patients in each cohort, and the IC/BPS HR was 1.599 (95% CI, 1.344-1.903; p < 0.0001). The average numbers of years until the development of IC/BPS in the IBS cohort and non-IBS cohort were 4.60 ± 2.58 (n = 253) and 5.99 ± 3.49 (n = 295) years, respectively.

IBS was shown to increase the risk of IC/BPS in this 12-year cohort study. The time from the diagnosis of IBS to IC/BPS was 5.35 ± 3.18 years. A common pathophysiology of IBS and IC/BPS is possible. Clinicians should be mindful of the association and promote collaborative care of these two elusive diseases.

IBS was shown to increase the risk of IC/BPS in this 12-year cohort study. The time from the diagnosis of IBS to IC/BPS was 5.35 ± 3.18 years. A common pathophysiology of IBS and IC/BPS is possible. Clinicians should be mindful of the association and promote collaborative care of these two elusive diseases.

Women seeking treatment for pelvic floor disorders (PFD) may have a high prevalence of frailty, which could potentially impact the risks of treatment. The present study was aimed to assess the prevalence of frailty in patients with PFD and additionally to compare post-treatment complications between frail and non-frail patients.

This is a prospective observational study conducted in a single secondary referral centre for PFD. Women with PFD and aged ≥ 65years were eligible for inclusion. Frailty was classified using a validated screening tool, the Groningen Frailty Indicator (GFI). The primary outcome was to determine the prevalence of frailty in elderly women with symptoms of pelvic floor disorders. Secondary outcomes were clinical outcomes after treatment between frail and non-frail patients.

A total of 263 women were included. The prevalence of frailty was 54.4% (143 women, 95% CI 48.1-60.5) in the studied group of patients. Frail patients had more comorbidities and used more medication compared to non-frail patients.