Food and Drug Administration Public Workshop Summary-Development Considerations of Antifungal Drugs to Address Unmet Medical Need.

Pressing challenges in the treatment of invasive fungal infections (IFIs) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics, clinical trial endpoints, prolonged trial duration, difficulties in patient recruitment, including subpopulations (eg, pediatrics), and heterogeneity of the IFIs. On 4 August 2020, the US Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This article summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development.

Oral Ibrexafungerp for Vulvovaginal Candidiasis Treatment: An Analysis of VANISH 303 and VANISH 306.

Background: Ibrexafungerp is a novel antifungal treatment for acute vulvovaginal candidiasis (VVC). Using pooled data from two phase three studies (VANISH 303 and 306) in the treatment of acute VVC, this analysis sought to determine the effectiveness of ibrexafungerp in various patient subgroups that may impact outcomes. Materials and Methods: Data from VANISH 303 (NCT03734991) and VANISH 306 (NCT03987620) evaluating ibrexafungerp 300 mg twice daily (BID) for 1 day versus placebo, were pooled and analyzed to determine clinical cure rate, clinical improvement, and mycological cure at the test-of-cure visit (day 11 ± 3) and symptom resolution at the follow-up visit (day 25 ± 4) in the overall population. Patient subgroups analyzed included race, body mass index (BMI), baseline vulvovaginal signs and symptoms (VSS) score, and Candida species. Results: At the test-of-cure visit, patients receiving ibrexafungerp, compared with those who received placebo, had significantly higher rates of clinical cure (56.9% [214/376 patients] vs. 35.7% [65/182 patients]), clinical improvement (68.4% [257/376 patients] vs. 45.1% [82/182 patients]), and mycological cure (54.0% [203/376 patients] vs. 24.2% [44/182 patients]; all p < 0.0001). At the follow-up visit, patients receiving ibrexafungerp had sustained responses with higher symptom resolution rates (66.8% [251/376 patients]) versus placebo (48.4% [88/182 patients]; p < 0.0001). Race, BMI, baseline VSS score (including VSS severity score 13-18), and Candida species infection did not adversely affect clinical cure rates. Safety analysis results were consistent with the individual studies. Conclusions: Ibrexafungerp provides a safe and well-tolerated first-in-class fungicidal, 1-day oral treatment for patients with acute VVC, the first new therapy in >20 years. Clinical Trial Registration Number: NCT03734991.

Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections.

Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as Aspergillus and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against Aspergillus spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician's armamentarium against these difficult-to-treat infections.

In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study.

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis. Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida. Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated. Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis. Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida.

Learning Curve for Laparoscopic Sleeve Gastrectomy: a Cumulative Summation (CUSUM) Analysis.

PURPOSE: Bariatric surgery is currently considered the most effective and durable treatment option for morbid obesity. Laparoscopic sleeve gastrectomy (LSG) has become a popular technique and may currently be the most frequently practiced surgical operation to treat obesity. However, no objective analyses of its learning curve have been reported. OBJECTIVE: to analyze the learning curve for LSG. MATERIALS AND METHODS: We included all LSGs performed in our hospital (University Hospital, Spain; Public Practice) from April 2013 to February 2016. The learning curve for LSG was evaluated using cumulative sum (CUSUM) analysis. All variables among the learning curve phases were compared. RESULTS: According to the CUSUM analysis, the learning curve was divided into three unique phases: early learning (the initial 26 patients), acquisition of skills (the middle 30 patients), and mastery of technique (the final 56 patients). The operative time and gastric stenosis significantly decreased with progression of the learning curve without differences in the 30-day postoperative complication rate, postoperative stay, or weight loss. CONCLUSION: According to this study, the learning curve for LSG can be divided into 3 distinct phases, and about 25 patients are needed to demonstrate an improvement in surgical skill.

FDA Public Workshop Summary-Coccidioidomycosis (Valley Fever): Considerations for Development of Antifungal Drugs.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.

Phase 2 Randomized Study of Oral Ibrexafungerp Versus Fluconazole in Vulvovaginal Candidiasis.

BACKGROUND: Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel, first-in-class oral triterpenoid glucan synthase inhibitor, has demonstrated broad fungicidal Candida activity and a favorable tolerability profile. The primary objective of this dose-finding study was to identify the optimal dose of oral ibrexafungerp in patients with acute vulvovaginal candidiasis. METHODS: Patients with vulvovaginal signs and symptoms score ≥7 were randomized equally to 6 treatments groups: 5 treatment doses of oral ibrexafungerp or oral fluconazole 150 mg. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms) at the test-of-cure visit (day 10). RESULTS: Overall, 186 patients were randomized into the 6 treatment groups. Results, using the modified intent-to-treat population (baseline positive culture), are reported for ibrexafungerp 300 mg twice daily (BID) for 1 day (n = 27), which was the dose selected for phase 3 studies, and fluconazole 150 mg for 1 day (n = 24). At day 10, the clinical cure rates for ibrexafungerp and fluconazole were 51.9% and 58.3%, respectively; at day 25, patients with no signs or symptoms were 70.4% and 50.0%, respectively. During the study ibrexafungerp patients required less antifungal rescue medications compared with fluconazole (3.7% vs 29.2%, respectively). Ibrexafungerp was well tolerated, with the most common treatment-related adverse events being mild gastrointestinal events. CONCLUSIONS: Ibrexafungerp is a well-tolerated novel antifungal with comparable efficacy to fluconazole in the treatment of acute vulvovaginal candidiasis. CLINICAL TRIALS REGISTRATION: NCT03253094.

Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303).

BACKGROUND: Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC. METHODS: Patients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4). RESULTS: Patients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity. CONCLUSIONS: Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

[Influence of the lockdown due to COVID-19 on weight-loss results during the first year after sleeve gastrectomy]. / Influencia del confinamiento por COVID-19 en los resultados ponderales durante el primer año tras la gastrectomía vertical.

INTRODUCTION: COVID-19 pandemic has lead to lockdown of population in many countries. In Spain, the state of alarm was established from March 15 to June 20, 2020. Usually this fact decreased people's mobility and physical activity, in addition to producing or exacerbating psychological disorders. Our aim was to determine the influence that this condition had over the short-term ponderal results of patients undergoing laparoscopic vertical gastrectomy from May 2019 to May 2020. METHODS: Case-control study for comparing the percentage of excess weight lost (%EWL) and the percentage of total weight lost (%TWL) of patients that underwent a VG during the last year, so they were affected by lockdown in April and part of March 2020 (group 1), to the %EWL and %TWL of a control group (group 2), obtained from our previous series. RESULTS: The mean %EWL in group 1 is 47,37 ± 18,59 and in group 2 is 51,13 ± 17,59, being p = 0,438. Meanwhile, the mean %TWL in group 1 is 21,14 ± 8,17 and in group 2 is 24,67 ± 8,01, with p = 0,115. CONCLUSIONS: Population lockdown by COVID-19 did not get worse short-term results of vertical gastrectomy. More studies with a larger number of patients are necessary to draw firm conclusions.

Influencia del confinamiento por COVID-19 en los resultados ponderales durante el primer año tras la gastrectomía vertical / Influence of the lockdown due to COVID-19 on weight-loss results during the first year after sleeve gastrectomy

Introducción: La pandemia por COVID-19ha obligado al confinamiento de la población en muchos países. En España, el estado de alarma se estableció desde el 15 de marzo al 20 de junio del 2020. Este hecho, por lo general, disminuyó la movilidad y la actividad física de las personas, además de producir o exacerbar alteraciones psicológicas. Nuestro objetivo es analizar la influencia que esta situación ha ejercido sobre los resultados ponderales a corto plazo de los pacientes tratados mediante una gastrectomía vertical laparoscópica entre mayo del 2019 y mayo del 2020. Métodos: Estudio de casos y controles donde se compararon el porcentaje de exceso de peso perdido (%EWL) y el porcentaje de peso total perdido (%TWL) de los pacientes intervenidos en el último año y a los que ha afectado el confinamiento durante el mes de abril y parte de marzo del 2020 (grupo 1; n=20), con el de un grupo control (grupo 2; n=40) de nuestra casuística previa. Resultados: El %EWL medio en el grupo 1 es de 47,37±18,59 y en el grupo 2 es de 51,13±17,59, siendo la p=0,438. Por su parte, el %TWL medio en el grupo 1 es de 21,14±8,17 mientras que en el grupo 2 es de 24,67±8,01, resultando la p=0,115. Conclusiones: El confinamiento de la población por COVID-19 no empeoró los resultados ponderales a corto plazo de la gastrectomía vertical. Son necesarios más estudios con un mayor número de pacientes para obtener conclusiones más sólidas. (AU)

Introduction: COVID-19 pandemic has lead to lockdown of population in many countries. In Spain, the state of alarm was established from March 15 to June 20, 2020. Usually this fact decreased people's mobility and physical activity, in addition to producing or exacerbating psychological disorders. Our aim was to determine the influence that this condition had over the short-term ponderal results of patients undergoing laparoscopic vertical gastrectomy from May 2019 to May 2020. Methods: Case-control study for comparing the percentage of excess weight lost (%EWL) and the percentage of total weight lost (%TWL) of patients that underwent a VG during the last year, so they were affected by lockdown in April and part of March 2020 (group 1), to the %EWL and %TWL of a control group (group 2), obtained from our previous series. Results: The mean %EWL in group 1 is 47,37±18,59 and in group 2 is 51,13±17,59, being p=0,438. Meanwhile, the mean %TWL in group 1 is 21,14±8,17 and in group 2 is 24,67±8,01, with p=0,115. Conclusions: Population lockdown by COVID-19 did not get worse short-term results of vertical gastrectomy. More studies with a larger number of patients are necessary to draw firm conclusions. (AU)

Influence of the lockdown due to COVID-19 on weight-loss results during the first year after sleeve gastrectomy.

INTRODUCTION: COVID-19 pandemic has lead to lockdown of population in many countries. In Spain, the state of alarm was established from March 15 to June 20, 2020. Usually this fact decreased people's mobility and physical activity, in addition to producing or exacerbating psychological disorders. Our aim was to determine the influence that this condition had over the short-term ponderal results of patients undergoing laparoscopic vertical gastrectomy from May 2019 to May 2020. METHODS: Case-control study for comparing the percentage of excess weight lost (%EWL) and the percentage of total weight lost (%TWL) of patients that underwent a VG during the last year, so they were affected by lockdown in April and part of March 2020 (group 1), to the %EWL and %TWL of a control group (group 2), obtained from our previous series. RESULTS: The mean %EWL in group 1 is 47.37±18.59 and in group 2 is 51.13±17.59, being P=.438. Meanwhile, the mean %TWL in group 1 is 21.14±8.17 and in group 2 is 24.67±8.01, with P=.115. CONCLUSIONS: Population lockdown by COVID-19 did not get worse short-term results of vertical gastrectomy. More studies with a larger number of patients are necessary to draw firm conclusions.

In Vitro pH Activity of Ibrexafungerp against Fluconazole-Susceptible and -Resistant Candida Isolates from Women with Vulvovaginal Candidiasis.

The vaginal environment with candidiasis has a pH of 3.8 to 4.5 and this has a negative effect on the activity of antifungals. Ibrexafungerp was evaluated against 187 Candida isolates, including fluconazole-sensitive and -resistant Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis with the media adjusted to pH 7.0 and pH 4.5. Ibrexafungerp MIC values were not adversely affected when tested at pH 4.5. Ibrexafungerp exhibited significant activity against all isolates at pH 4.5.

Ibrexafungerp, a Novel Oral Triterpenoid Antifungal in Development: Overview of Antifungal Activity Against Candida glabrata.

Systemic infections caused by Candida species are an important cause of morbidity and mortality among immunocompromised and non-immunocompromised patients. In particular, Candida glabrata is an emerging species within the Candida family that causes infections ranging from superficial to life-threatening systemic disease. Echinocandins and azoles are typically the first-line therapies used to treat infections caused by C. glabrata, however, there is an increasing prevalence of resistance to these antifungal agents in patients. Thus, a need exists for novel therapies that demonstrate high efficacy against C. glabrata. Ibrexafungerp is a first-in-class glucan synthase inhibitor with oral availability developed to address this increasing antifungal resistance. Ibrexafungerp demonstrates broad in vitro activity against wild-type, azole-resistant, and echinocandin-resistant C. glabrata species. Furthermore, ibrexafungerp has shown efficacy in low pH environments, which suggests its potential effectiveness in treating vulvovaginal candidiasis. Additional preclinical and clinical studies are needed to further examine the mechanism(s) of ibrexafungerp, including acting as a promising new agent for treating C. glabrata infections.

Endoscopic treatment of postoperative esophagogastric leaks with fully covered self-expanding metal stents

BACKGROUND: the management of postoperative esophageal leaks is a huge therapeutic challenge. Thanks to the advances in endoscopy, treatment with esophageal stents has been proposed as a valid option. AIMS: the main objective of the study was to evaluate the effectiveness and safety of the use of fully covered esophageal metal stents in the treatment of postoperative esophageal leaks. METHODS: a retrospective observational study was performed in patients with postoperative esophageal leaks, treated with fully covered self-expandable metal stents between June 2011 and May 2018. RESULTS: twenty-five patients were evaluated and 34 stents were placed. The closure of the leak was observed in 21 patients after removal of the stent, with an overall technical success rate of 84 %. The mean time with a stent placed for closure of the fistula was 55.7 ± 27.11 days/patient (mean of 39 ± 24.30 days/stent). The most frequent complication was a partial distal stent migration (7/34 stents), followed by five cases of complete migration into the stomach. CONCLUSIONS: endoscopic treatment with fully covered selfexpandable metal stents seems to be an effective and safe first-line treatment for postoperative esophageal leaks, according to the experience in our center

No disponible

Endoscopic treatment of postoperative esophagogastric leaks with fully covered self-expanding metal stents.

BACKGROUND: the management of postoperative esophageal leaks is a huge therapeutic challenge. Thanks to the advances in endoscopy, treatment with esophageal stents has been proposed as a valid option. AIMS: the main objective of the study was to evaluate the effectiveness and safety of the use of fully covered esophageal metal stents in the treatment of postoperative esophageal leaks. METHODS: a retrospective observational study was performed in patients with postoperative esophageal leaks, treated with fully covered self-expandable metal stents between June 2011 and May 2018. RESULTS: twenty-five patients were evaluated and 34 stents were placed. The closure of the leak was observed in 21 patients after removal of the stent, with an overall technical success rate of 84 %. The mean time with a stent placed for closure of the fistula was 55.7 ± 27.11 days/patient (mean of 39 ± 24.30 days/stent). The most frequent complication was a partial distal stent migration (7/34 stents), followed by five cases of complete migration into the stomach. CONCLUSIONS: endoscopic treatment with fully covered self-expandable metal stents seems to be an effective and safe first-line treatment for postoperative esophageal leaks, according to the experience in our center.

Are We Ready for Bariatric Surgery in a Liver Transplant Program? A Meta-Analysis.

BACKGROUND: Obesity-related non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are two main causes of end-stage liver disease requiring a liver transplantation. Studies exploring bariatric surgery in the liver transplantation setting have increased in recent years; however, a systematic analysis of the topic is lacking to date. This meta-analysis was conducted to explore the perioperative and long-term outcomes of bariatric surgery in obese patients undergoing liver transplantation. METHODS: Electronic databases were systematically searched for studies reporting bariatric surgery in patients undergoing liver transplantation. The primary outcomes were postoperative complications and mortality. We also extracted data about excess weight loss, body mass index, and improvement of comorbidities after bariatric surgery. RESULTS: A total of 96 patients from 8 articles were included. Bariatric surgery-related morbidity and mortality rates were 37% (95% CI 0.27-0.47) and 0.6% (95% CI 0.02-0.13), respectively. Body mass index at 24 months was 31.02 (95% CI 25.96-36.09) with a percentage excess weight loss at 12 and 24 months of 44.08 (95% CI 27.90-60.26) and 49.2 (95% CI 31.89-66.66), respectively. After bariatric surgery, rates of improvement of arterial hypertension and diabetes mellitus were 61% (95% CI 0.45-0.75) and 45% (95% CI 0.25-0.66), respectively. In most patients, bariatric surgery was performed after liver transplant and the most frequent technique was sleeve gastrectomy. CONCLUSIONS: Bariatric surgery can be performed safely in the setting of liver transplantation resulting in improvement of obesity-related comorbidities. The optimal timing and technique require further studies.

Case report of Tourniquet ALPPS and simultaneous sleeve gastrectomy: A valuable association to achieve an adequate future liver remnant in obese patients.

INTRODUCTION: Obesity represents a risk factor in case of major hepatectomy, because the future liver remnant (FLR) must be proportional with body weight. To avoid post-hepatectomy liver failure, and further increase the ratio between FLR and body weight, we performed a bariatric procedure in the first stage of the ALPPS technique. PATIENT CONCERNS: Fifty-four-year-old woman, with morbid obesity (BMI 58.5) and type II diabetes mellitus, was scheduled for a major hepatectomy due to multiple colorectal liver metastases DIAGNOSIS:: Six months before, the patient was diagnosed with colorectal cancer and synchronous liver metastases. She was initially treated with sigmoidectomy and chemotherapy. After partial response of the liver metastases, we considered a liver resection but the FLR was very low, especially in relation to her BMI. INTERVENTION: We planned a novel approach and, for the first time, we performed a sleeve gastrectomy during the first stage of Tourniquet ALPPS (T-ALPPS). After achieving an adequate FLR, we successfully completed the major hepatectomy during the second stage of T-ALPPS. OUTCOME: The association between sleeve gastrectomy and T-ALPPS produced an increase of FLR/body weight ratio up to 0.8 that allowed completing a right trisectionectomy in the second stage of ALPPS. The major hepatectomy was performed without severe complications, and several months after surgery the patient is still alive without any recurrence Conclusion: Despite obesity represents a risk factor involved in the carcinogenesis, the role of the bariatric surgery in the oncological setting is not well established. In this clinical case, we benefited from the weight loss produced by bariatric surgery combined with an effective hypertrophy technique and chemotherapy. These findings suggest that bariatric surgery could be useful for obese patients with liver malignancy and need for extended hepatectomy.

Oral Ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis.

INTRODUCTION: Vulvovaginal candidiasis (VVC) is a common fungal infection caused by predominantly Candida albicans, and is diagnosed in up to 40% of women with vaginal complaints in the primary care setting. Approximately 75% of women experience at least one episode during their reproductive years. AREAS COVERED: Ibrexafungerp is an orally active, semi-synthetic triterpenoid glucan synthase inhibitor under development for treatment and prevention of VVC. We present the chemistry, mechanism of action, pharmacology, microbiology, and results from clinical studies with ibrexafungerp in women with VVC. EXPERT OPINION: Ibrexafungerp addresses several unmet needs with existing antifungal drugs as a first in a new class of antifungal agents with a novel mechanism of action demonstrating no antifungal cross resistance with azoles, and fungicidal activity against Candida spp., including fluconazole-resistant species. Some of the key attributes of ibrexafungerp related to VVC include oral one-day dosing, high tissue penetration, enhanced activity at low pH seen in the vagina, low risk for clinically significant drug-drug interactions, and a low risk of adverse events. If approved, ibrexafungerp will be the first new antifungal agent available for the treatment of VVC in more than 20 years and the only oral, non-azole antifungal approved for women suffering from VVC.

Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections.

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-ß-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC50 and MIC90) values in >400 C. auris isolates were 0.5 µg/mL and 1.0 µg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections.

Hemorragia digestiva alta por malformación arteriovenosa pancreática tratada exitosamente mediante embolización transarterial / No disponible

No disponible