Equitable inclusion of diverse populations in oncology clinical trials: deterrents and drivers.

The burden of cancer exerts a disproportionate impact across different regions and population subsets. Disease-specific attributes, coupled with genetic and socioeconomic factors, significantly influence cancer treatment outcomes. Precision oncology promises the development of safe and effective options for specific ethnic phenotypes and clinicodemographic profiles. Currently, clinical trials are concentrated in resource-rich geographies with younger, healthier, white, educated, and empowered populations. Vulnerable and marginalized people are often deprived of opportunities to participate in clinical trials. Despite consistent endeavors by regulators, industry, and other stakeholders, factors including diversity in trial regulations and patient and provider-related cultural, logistic, and operational barriers limit the inclusiveness of clinical trials. Understanding and addressing these constraints by collaborative actions involving regulatory initiatives, industry, patient advocacy groups, community engagement in a culturally sensitive manner, and designing and promoting decentralized clinical trials are vital to establishing a clinical research ecosystem that promotes equity in the representation of population subgroups.

[Antibiotic resistance changes in episodes of symptomatic bacteriospermia: development in a health area of southeast Spain]. / Cambios en la resistencia antibiótica en episodios de bacteriospermia sintomática: Evolución en un área de salud del sudeste español.

OBJECTIVE: Chronic bacterial prostatitis (CBP) is an entity of difficult clinical diagnosis and treatment, being the microbiological study of semen the main diagnostic test. This study aimed to determine the etiology and antibiotic resistance in patients with symptomatic bacteriospermia (SBP) in our environment. METHODS: A cross-sectional and retrospective descriptive study has been carried out from a Regional Hospital of the Spanish Southeast. The participants were patients assisted in the consultations of the Hospital with clinic compatible with CBP, between 2016 and 2021. The interventions were collection and analysis of the results derived from the microbiological study of the semen sample. The main determinations were the etiology and rate of antibiotic resistance of BPS episodes are analyzed. RESULTS: The main isolated microorganism is Enterococcus faecalis (34.89%), followed by Ureaplasma spp. (13.74%) and Escherichia coli (10.98%). The rate of antibiotic resistance of E. faecalis to quinolones (11%) is lower than previous studies, while for E. coli it has been higher (35%). The low rate of resistance shown by E. faecalis and E. coli to fosfomycin and nitrofurantoin stands out. CONCLUSIONS: In the SBP, gram-positive and atypical bacteria are established as the main causative agents of this entity. This forces us to rethink the therapeutic strategy used, which will avoid the increase in antibiotic resistance, recurrences, and chronicity of this pathology.

[Microbial etiology of bacterial chronic prostatitis: systematic review]. / Etiología microbiana de la prostatitis crónica bacteriana: revisión sistemática.

OBJECTIVE: The importance of Gram-positive microorganisms and atypical bacteria in chronic bacterial prostatitis (CBP) has recently been described. For this reason, this study analyzes the etiology of CBP, as well as the evolution of antibiotic resistance through a systematic review. METHODS: A systematic review of studies obtained through the MEDLINE (PubMed) database, related to the etiology and antibiotic resistance profile of CBP, published up July 1, 2021. RESULTS: The most frequent isolated microorganisms that we have found in publications are Enterococcus faecalis (46.90%), Staphylococcus spp. (22.30%), Escherichia coli (15.09%) and atypical bacteria (6.04%). CONCLUSIONS: CBP is undergoing and unprecedented change of paradigm. Gram-positive bacteria and atypical bacteria are the main pathogens involved in the aetiology of this entity. This forces us to rethink the therapeutic strategy used, since it is necessary to use antibiotics that assume the etiological change and the profile of antibiotic resistance described.

Nomofobia. Enfermedades del siglo XXI / Nomophobia: Disorder of the 21st Century

No disponible

Single-stage treatment with intraoperative ERCP: management of patients with possible choledocholithiasis and gallbladder in situ in a non-tertiary Spanish hospital.

BACKGROUND: The best way to reduce endoscopic retrograde cholangiopancreatography (ERCP) complications is not to perform it if it is unnecessary. Both intraoperative and postoperative ERCP rely on use of intraoperative cholangiography as a final diagnostic test for choledocholithiasis (CLD) whenever clinical data are unable to rule out CLD. Intraoperative ERCP could become a therapeutic option when a previous preoperative ERCP fails. We present our experience with intraoperative ERCP. PATIENTS AND METHODS: This is a descriptive and prospective study of a cohort of 82 patients with moderate risk of CLD. They were operated on by laparoscopic cholecystectomy with intraoperative cholangiography (IOC). We performed intraoperative ERCP using the rendezvous technique. RESULTS: Thirty-six out of 82 patients had an abnormal IOC study. Mean age was 58.7 years (standard deviation, SD 16.6, 25-83 years), and 60.6% were females. Ultrasound study showed that 51.4% of patients had a dilated bile duct. Magnetic resonance cholangiography (MRC) was performed on three patients (8.3%). The success rate of intraoperative ERCP was 88.2%. Three out of the 36 patients (8.8%) had ERCP complications [2 mild papillary bleeding (5.8%), 1 acute pancreatitis (2.9%)]. The rate of conversion to open surgery was 5% with a surgical complications rate of 4% [one injured duct and two surgical bleeding which required re-operation (2.5%)]. There were no mortalities. Four patients (11.1%) needed post-surgical ERCP, with a residual CLD rate of 5.6% (two patients) in the postoperative period. Mean surgical time was 181 min (SD 60, 75-345 min). Mean hospital stay was 6.2 days (SD 4.7, 2-24 days). CONCLUSIONS: Intraoperative ERCP is an option to prevent performing ERCP unnecessarily on patients with moderate risk of CLD not confirmed using appropriate radiological studies. It can resolve the biliary disease in a single step with a similar success rate to standard ERCP, but with low morbidity, especially of acute pancreatitis. The residual CLD rate is also very low.

A Phase I study of infusional vinblastine in combination with the P-glycoprotein antagonist PSC 833 (valspodar).

BACKGROUND: PSC 833 is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance (MDR). The authors conducted a Phase I study of orally administered PSC 833 in combination with vinblastine administered as a 5-day continuous infusion. METHODS: Seventy-nine patients with advanced malignant disease were enrolled in the trial and treated with escalating doses of PSC 833. Pharmacokinetic interactions between PSC 833 and vinblastine were anticipated. Accordingly, when dose limiting toxicities were observed, the dose of vinblastine was reduced as PSC 833 was escalated. Three schedules and two formulations of PSC 833 were used in the study. RESULTS: The maximum tolerated doses of PSC 833 were 12.5 mg/kg orally every 12 hours for 8 days for the liquid formulation in combination with 0.9 mg/m(2) per day vinblastine as a continuous intravenous infusion (CIV) for 5 days; and 4 mg/kg orally every 6 hours for 8 days for the microemulsion formulation in combination with 0.6 mg/m(2) per day vinblastine CIV for 5 days. The principal toxicities for PSC 833 were ataxia and paresthesias and for the combination, constipation, fever. and neutropenia. Increased oral bioavailability and increased peak and trough concentrations were observed with the microemulsion formulation. Significant interpatient variability in pharmacokinetic parameters was observed. Ten patients studied at the MTD for PSC 833 (4 mg/kg orally every 6 hours for 8 days) had inhibition of rhodamine efflux from CD56 positive peripheral lymphocytes as a surrogate for Pgp antagonism. Among 43 evaluable patients with clear cell carcinoma of the kidney, 3 patients had complete responses, and 1 patient had a partial response. CONCLUSIONS: PSC 833 in combination with vinblastine can be administered safely to patients provided the vinblastine dose is adjusted for pharmacokinetic interactions. The high interpatient variability is a significant confounding factor. Surrogate studies with CD56 positive cells suggest that Pgp inhibition in the clinical setting is achievable. Improved methods for predicting pharmacokinetic interactions should improve future studies.

Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833.

PURPOSE: PSC 833 (valspodar) is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance. We conducted a phase I study of a 7-day oral administration of PSC 833 in combination with paclitaxel, administered as a 96-hour continuous infusion. PATIENTS AND METHODS: Fifty patients with advanced cancer were enrolled onto the trial. PSC 833 was administered orally for 7 days, beginning 72 hours before the start of the paclitaxel infusion. Paclitaxel dose reductions were planned because of the pharmacokinetic interactions known to occur with PSC 833. RESULTS: In combination with PSC 833, maximum-tolerated doses were defined as paclitaxel 13.1 mg/m(2)/d continuous intravenous infusion (CIVI) for 4 days without filgrastim, and paclitaxel 17.5 mg/m(2)/d CIVI for 4 days with filgrastim support. Dose-limiting toxicity for the combination was neutropenia. Statistical analysis of cohorts revealed similar mean steady-state concentrations (C(pss)) and areas under the concentration-versus-time curve (AUCs) when patients received paclitaxel doses of 13.1 or 17.5 mg/m(2)/d for 4 days with PSC 833, as when they received a paclitaxel dose of 35 mg/m(2)/d for 4 days without PSC 833. However, the effect of PSC 833 on paclitaxel pharmacokinetics varied greatly among individual patients, although a surrogate assay using CD56+ cells suggested inhibition of Pgp was complete or nearly complete at low concentrations of PSC 833. Responses occurred in three of four patients with non-small-cell lung cancer, and clinical benefit occurred in five of 10 patients with ovarian carcinoma. CONCLUSION: PSC 833 in combination with paclitaxel can be administered safely to patients provided the paclitaxel dose is reduced to compensate for the pharmacokinetic interaction. Surrogate studies with CD56+ cells indicate that the maximum-tolerated dose for PSC 833 gives serum levels much higher than those required to block Pgp. The variability in paclitaxel pharmacokinetics, despite complete inhibition of Pgp in the surrogate assay, suggests that other mechanisms, most likely related to P450, contribute to the pharmacokinetic interaction. Future development of combinations such as this should include strategies to predict pharmacokinetics of the chemotherapeutic agent. This in turn will facilitate dosing to achieve comparable CPss and AUCs.

SmcL, a novel membrane-damaging virulence factor in Listeria.

We describe here the fourth listerial membrane-damaging virulence factor, a sphingomyelinase C (SMase) that is produced specifically by the ruminant pathogen Listeria ivanovii. Its coding gene, smcL, is a monocistron expressed independently of PrfA. The smcL product, SmcL, is highly similar to the staphylococcal beta-toxin and is responsible for the differential hemolytic properties of L. ivanovii (bizonal hemolysis and CAMP-like reaction with R. equi). The role of SmcL in virulence was assessed by gene disruption and complementation. Our data show that SmcL mediates disruption of the membrane of primary phagosomes, thereby promoting bacterial intracellular proliferation. They also suggest that SmcL may play a role in host tropism. smcL is located in LIPI-2, a novel 18-kb pathogenicity island which also contains a cluster of internalin genes. LIPI-2 is unstable, L. ivanovii-specific and required for full virulence in mice and lambs.