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Experience with Rifabutin-Containing Therapy in 500 Patients from the European Registry on Helicobacter pylori Management (Hp-EuReg).
No full textFirst-line Helicobacter pylori (H. pylori) treatments have been relatively well evaluated; however, it remains necessary to identify the most effective rescue treatments. Our aim was to assess the effectiveness and safety of H. pylori regimens containing rifabutin. International multicentre prospective non-interventional European Registry on H. pylori Management (Hp-EuReg). Patients treated with rifabutin were registered in AEG-REDCap e-CRF from 2013 to 2021. Modified intention-to-treat and per-protocol analyses were performed. Data were subject to quality control. Overall, 500 patients included in the Hp-EuReg were treated with rifabutin (mean age 52 years, 72% female, 63% with dyspepsia, 4% with peptic ulcer). Culture was performed in 63% of cases: dual resistance (to both clarithromycin and metronidazole) was reported in 46% of the cases, and triple resistance (to clarithromycin, metronidazole, and levofloxacin) in 39%. In 87% of cases rifabutin was utilised as part of a triple therapy together with amoxicillin and a proton-pump-inhibitor, and in an additional 6% of the patients, bismuth was added to this triple regimen. Rifabutin was mainly used in second-line (32%), third-line (25%), and fourth-line (27%) regimens, achieving overall 78%, 80% and 66% effectiveness by modified intention-to-treat, respectively. Compliance with treatment was 89%. At least one adverse event was registered in 26% of the patients (most frequently nausea), and one serious adverse event (0.2%) was reported in one patient with leukopenia and thrombocytopenia with fever requiring hospitalisation. Rifabutin-containing therapy represents an effective and safe strategy after one or even several failures of H. pylori eradication treatment
Differences Between Takotsubo and the Working Diagnosis of Myocardial Infarction With Nonobstructive Coronary Arteries.
No full textWhether Takotsubo syndrome (TTS) should be classified within myocardial infarction with non-obstructive coronary arteries (MINOCAs) is still controversial. The aim of this work was to evaluate the main differences between TTS and non-TTS MINOCAs. A cohort study based on two prospective registries: TTS from the RETAKO registry (N:1,015) and patients with non-TTS MINOCAs from contemporary records of acute myocardial infarction from five 5 national centers (N:1,080). Definitions and management recommended by the ESC were used. Survival analysis was based on the Cox regression analysis; propensity score matching (PS) was created to adjust prognostic variables. Takotsubo syndrome were more often women (85.9 vs. 51.9%; p Compared to the rest of MINOCAs, TTS presents a different patient profile and a more aggressive acute phase. However, its long-term cardiovascular prognosis is better. These results support that TTS should be considered a separate entity with unique characteristics and prognosis
Cost-Effectiveness of Robotic vs. Laparoscopic Surgery for Different Surgical Procedures: Protocol for a Prospective, Multicentric Study (ROBOCOSTES).
No full textThe studies which address the impact of costs of robotic vs. laparoscopic approach on quality of life (cost-effectiveness studies) are scares in general surgery. The Spanish national study on cost-effectiveness differences among robotic and laparoscopic surgery (ROBOCOSTES) is designed as a prospective, multicentre, national, observational study. The aim is to determine in which procedures robotic surgery is more cost-effective than laparoscopic surgery. Several surgical operations and patient populations will be evaluated (distal pancreatectomy, gastrectomy, sleeve gastrectomy, inguinal hernioplasty, rectal resection for cancer, Heller cardiomiotomy and Nissen procedure). The results of this study will demonstrate which treatment (laparoscopic or robotic) and in which population is more cost-effective. This study will also assess the impact of previous surgical experience on main outcomes
Traditional Medicinal Plants as a Source of Inspiration for Osteosarcoma Therapy
No full textOsteosarcoma is one of the most common types of bone cancers among paediatric patients. Despite the advances made in surgery, chemo-, and radiotherapy, the mortality rate of metastatic osteosarcoma remains unchangeably high. The standard drug combination used to treat this bone cancer has remained the same for the last 20 years, and it produces many dangerous side effects. Through history, from ancient to modern times, nature has been a remarkable source of chemical diversity, used to alleviate human disease. The application of modern scientific technology to the study of natural products has identified many specific molecules with anti-cancer properties. This review describes the latest discovered anti-cancer compounds extracted from traditional medicinal plants, with a focus on osteosarcoma research, and on their cellular and molecular mechanisms of action. The presented compounds have proven to kill osteosarcoma cells by interfering with different pathways: apoptosis induction, stimulation of autophagy, generation of reactive oxygen species, etc. This wide variety of cellular targets confer natural products the potential to be used as chemotherapeutic drugs, and also the ability to act as sensitizers in drug combination treatments. The major hindrance for these molecules is low bioavailability. A problem that may be solved by chemical modification or nano-encapsulation
Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice.
No full textKiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function.This work was supported by grants BFU2014-57581-P, BFU2017-83934-
P, and PID2020-118660GB-I00 (to M.T.-S.—Ministerio de Economía y Competitividad, Spain; co-funded with EU funds from FEDER Program); Project PIE-00005 (to M.T.-S) and grants PI16/01243 and PI19/00257 (to J.R.—Instituto de Salud Carlos III, Ministerio de Sanidad, Spain; cofunded with EU funds from FEDER Program); Project P12-FQM-01943 (to M.T.-S.—Junta de Andalucía, Spain); Project REP-655232 (ReprObesity; to M.T.-S.–European Union); and COST Action BM1105 (to M.T.-S. and V.P.–European Union). CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of Instituto de Salud Carlos III, Spain. The authors are indebted to Dr. Esther Peralbo, Head of the Cytometry Unit of IMIBIC, for her superb assistance in the optimization and implementation of protocols of FACS for Kiss1 neuronal isolation. The assistance of Profs. Catherine Dulac and Robert A. Steiner for providing the parental Kiss1Cre/− and GnRH-Crepos mouse lines is cordially appreciated.S
Safety in Dermatologic Procedures: Ophthalmologic Complications
No full textOphthalmological complications are uncommon in dermatologic surgery. Nonetheless, all surgeons should know the basics of recognizing, preventing, and treating the 4 complications addressed in this article from the series 'Safety in Dermatologic Procedures'. The first complication that surgeons should be familiar with is eye damage due to chemical irritants. This is a common complication in operating rooms given the presence of irritant substances and the performance of procedures in the eyebrow and eyelid region. The second complication is laser-induced eye damage. In this case, eye protection with safety glasses or eye caps is crucial. The third complication is accidental eyeball perforation, which can occur during certain surgical procedures. The fourth and final complication is retinal artery vasospasm or embolism due to drugs or fitter materials. This complication is rare but important to recognize, as early treatment can prevent permanent blindness. (C) 2022 AEDV. Published by Elsevier Espana, S.L.U
Hidradenitis suppurativa and suicide risk: a multivariate analysis in a disease with a high psychological burden.
No full textHidradenitis suppurativa (HS) is a disorder that can lead to serious sequelae and important comorbidities. It has been associated with different mental health conditions, such as depression, anxiety or completed suicide. The objective is to analyze the suicide risk (SR) among patients in a monographic HS consultation, as well as to establish individual association factors. Patients older than 18 years seen in our specific HS unit were consecutively included and invited to respond to the self-administered Beck hopelessness scale. Those patients with significant intellectual disabilities or severe mental health conditions, including a history of psychosis, were excluded. In addition, data related to the skin process were collected. Subsequently, it was studied whether there were significant differences between patients with absent-mild SR and those with moderate-severe SR and a logistic regression analysis was performed to determine the relationship of these variables with SR. A total of 136 patients were included in the study, 51.5% men. Of them, 21.3% presented a moderate or severe SR (score ≥ 9 in the Beck test). This risk was significantly related to having a previous or concomitant psychiatric disorder (OR = 2.586, 95% CI 1.044-6.409, p = 0.040) followed by the history of biological treatment (OR = 2.867, 95% CI 1.004-8.182, p = 0.049). The existence of other affected relatives was confirmed as a protective factor (OR = 0.377, 95% CI 0.150-0.951, p = 0.039). The prevalence of SR in patients with HS is higher than that of the general Spanish population. The presence of a psychiatric disorder and the need for biological treatment are established as factors that increase SR, both of which can be interpreted as a more advanced disease. As a protective factor, the presence of other cases in the family is established, which suggests a greater normalization of the disease
Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.
No full textInformation about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.S
Left bundle branch area pacing in patients with heart failure and right bundle branch block: Results from International LBBAP Collaborative-Study Group
No full textCardiac resynchronization therapy (CRT) using biventricular pacing has limited efficacy in patients with heart failure (HF) and right bundle branch block (RBBB). Left bundle branch area pacing (LBBAP) is a novel physiologic pacing option. OBJECTIVE The aim of the study was to assess the feasibility and outcomes of LBBAP in HF patients with RBBB and reduced left ventricular systolic function, and indication for CRT or ventricular pacing. METHODS LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) = 5% increase in ejection fraction) to LBBAP were assessed. RESULTS LBBAP was attempted in 121 patients and successful in 107 (88%). Patient characteristics included age 74 +/- 12 years, female 25%, ischemic cardiomyopathy 49%, and ejection fraction 35% +/- 9%. QRS axis at baseline was normal in 24%, left axis 63%, right axis 13%. LBBAP threshold and R-wave amplitudes were 0.8 +/- 0.3 V@ 0.5 ms and 10 +/- 9 mV at implant and remained stable during mean follow-up of 13 +/- 8 months. LBBAP resulted in narrowing of QRS duration (156 +/- 20 ms to 150 +/- 24 ms (P = .01) with R-wave peak times in V-6 of 85 +/- 16 ms. LVEF improved from 35% +/- 9% to 43% +/- 12% (P,.01). Clinical and echocardiographic response was observed in 60% and 61% of patients, respectively. Female sex and reduction in QRS duration with LBBAP were predictive of echocardiographic response and super-response. CONCLUSION LBBAP is a feasible alternative to deliver CRT or physiologic ventricular pacing in patients with RBBB, HF, and LV dysfunction
Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial.
No full textMen with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity. We did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18-50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL). In the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin -2.4, 95 % CI -4.1 to -0.8, p = 0.004; testosterone -2.7, 95 % CI -4.3 to -1.1, p = 0.001; combination -3.4, 95 % CI -5.0 to -1.8, p Among men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.The authors wish to thank all the study participants for their collaboration and Maria Repice for English language editing of this article. Also, the authors thank Bayer Pharma AG for the donation of testosterone undecanoate and matching placebo. JCFG was supported by a research contract from the Servicio Andaluz de Salud, Spain (SAS; B0003-2017) and by an intensification research program (INT21/00078, Instituto de Salud Carlos III, Spain; co-funded by the Fondo Europeo de Desarrollo Regional-FEDER); BRM was supported by the Miguel Servet Type I program (CP19/00098, Instituto de Salud Carlos III, Spain; cofunded by the Fondo Europeo de Desarrollo Regional-FEDER); MMV was supported by a Rio Hortega grant from the Instituto de Salud Carlos III, Spain (CM18/00120); EMYS was the recipient of the Nicolas Monardes Programme from the Servicio Andaluz de Salud, Junta de Andalucia, Spain (C1-0005-2019). This work was supported by a grant from Servicio Andaluz de Salud (PI-0173-2013). The funding organization played no role in the design and performance of the study, choice of enrolled subjects, review and interpretation of the data, or final approval of the manuscript.S