Mitochondrial Dysfunction in Intensive Care Unit Patients.

BACKGROUND: In patients admitted to the Intensive Care Unit (ICU), mortality is high due to multiple organ damage. Mitochondrial dysfunction and impaired oxygen consumption, as causative mechanisms, play a significant role in reducing the activity of immune cells in sepsis, resulting in the progression of the multiple organ dysfunction syndromes (MODS). The evaluation of mitochondrial function in critical care patients in the immune cells, especially in lymphocytes, could reveal the target point that determines mitochondrial failure. OBJECTIVE: To find the relationship between mitochondrial reactive oxygen species production (mROS), mitochondrial membrane potential (ΔΨm), and mitochondrial oxygen consumption (mVO2) in peripheral plasma lymphocytes collected from ICU patients. We also compared these three characteristic mitochondrial functions with C-reactive protein (CRP), serum lactate, and central venous saturation (SvO2) that would enable the prediction of the ultimate outcome. METHODS: Isolated lymphocytes from 54 critical care patients with SIRS by sepsis and non-sepsis etiologies were analyzed with flow cytometry by staining with dihydroethidium and JC-1, measuring mROS, ΔΨm, and mVO2. Clinical variables, such as serum lactate (mmol/L) and C-reactive protein (mg/L) from peripheral blood, were measured in the first 24 hours of admission. A confounding analysis was performed using logistic regression, and a p-value of <0.05 was considered statistically significant. RESULTS: It has been confirmed that there is a drastic increase in reactive oxygen species (ROS) and mVO2 in critically ill patients immediately after exposure to the insult pathogen-associated molecular pattern /damageassociated molecular pattern (PAMPS/DAMPS) and continued for the first 24 hours thereafter. The results showed no significant alterations in the mitochondrial membrane potential (ΔΨm) compared with the lymphocytes in controls. A significant correlation between CRP and SvO2 and a strong positive relationship between CRP, values above 3 mg/l, and white blood cells were observed. CONCLUSION: Lymphocytes from patients with SIRS displayed higher mitochondrial respiratory capacities and reactive oxygen species production compared with controls. Clinical markers of inflammation indirectly evaluate the mitochondrial function, most of which have been validated in a clinical setting.

Two-year results of intermittent electrical stimulation of the lower esophageal sphincter treatment of gastroesophageal reflux disease.

BACKGROUND: Lower esophageal sphincter (LES) electrical stimulation therapy (EST) has been shown to improve outcome in gastroesophageal reflux disease (GERD) patients at 1 year. The aim of this open-label extension trial (NCT01578642) was to study the 2-year safety and efficacy of LES-EST in GERD patients. METHODS: GERD patients responsive partially to proton pump inhibitors (PPI) with off-PPI GERD health-related quality of life (HRQL) of ≥20, 24-hour esophageal pH ≤4.0 for >5% of the time, hiatal hernia ≤3 cm, and esophagitis LA grade C or lower participated in this trial. Bipolar stitch electrodes and a pulse generator (EndoStim BV, The Hague, The Netherlands) were implanted laparoscopically. LES-EST at 20 Hz, 215 µs, 3-8 mAmp was delivered over 30-minute sessions, 6-12 sessions per day, starting on day 1 after implantation. Patients were evaluated using GERD-HRQL, symptom diaries, Short Form-12, and esophageal pH testing at regular intervals. Stimulation sessions were optimized based on residual symptoms and esophageal pH at follow-up. RESULTS: Twenty-five patients (mean age [SD] = 52 [12] years; 14 men) were implanted successfully; 23 patients participated in the 2-year extension trial, and 21 completed their 2-year evaluation. At 2 years, there was improvement in their median GERD-HRQL on LES-EST compared with both their on-PPI (9 vs 0; P = .001) and off-PPI (23.5 vs. 0; P < .001) baseline scores. Median 24-hour distal esophageal acid exposure improved from 10% at baseline to 4% (per-protocol analysis; P < .001) at 2 years with 71% demonstrating either normalization or a ≥50% decrease in their distal esophageal acid exposure. All except 5 patients (16/21) reported complete cessation of PPI use; only 2 patients were using a PPI regularly (≥50% of days). There was significant improvement in sleep quality and daily symptoms of heartburn and regurgitation on LES-EST. At baseline, 92% of the subjects (22/24) reported that they were "unsatisfied" with their condition off-PPI and 71% (17/24) on-PPI compared with 0% (0/21) "unsatisfied" at the 24-month visits on LES-EST. There were no device- or therapy-related serious adverse events and no untoward sensation or dysphagia reported with LES-EST. CONCLUSION: LES-EST is safe and effective for treating patients with GERD over a period of 2 years. LES-EST resulted in a significant and sustained improvement in GERD symptoms, and esophageal acid exposure and eliminated PPI use in majority of patients (16 of 21). Further, LES-EST was not associated with any gastrointestinal side effects or adverse events.

Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: final results of open-label prospective trial.

BACKGROUND: Electrical stimulation of the lower esophageal sphincter (LES) improves LES pressure without interfering with LES relaxation. The aim of this open-label pilot trial was to evaluate the safety and efficacy of long-term LES stimulation using a permanently implanted LES stimulator in patients with gastroesophageal reflux disease (GERD). METHODS: GERD patients who were at least partially responsive to proton pump inhibitors (PPI) with abnormal esophageal pH, hiatal hernia ≤ 3 cm, and esophagitis ≤ LA grade C were included. Bipolar stitch electrodes were placed in the LES and an IPG was placed in a subcutaneous pocket. Electrical stimulation was delivered at 20 Hz, 215 µs, 3-8 mA in 30 min sessions. The number and timing of sessions was tailored to each patient's GERD profile. Patients were evaluated using GERD-HRQL, daily symptom and medication diaries, SF-12, esophageal pH, and high-resolution manometry. RESULTS: 24 patients (mean age = 53 years, SD = 12 years; 14 men) were implanted; 23 completed their 6-month evaluation. Median GERD-HRQL scores at 6 months was 2.0 (IQR = 0-5.5) and was significantly better than both baseline on-PPI [9.0 (range = 6.0-10.0); p < 0.001] and off-PPI [23 (21-25); p < 0.001] GERD-HRQL. Median% 24-h esophageal pH < 4.0 at baseline was 10.1 and improved to 5.1 at 6 months (p < 0.001). At their 6-month follow-up, 91 % (21/23) of the patients were off PPI and had significantly better median GERD-HRQL on LES stimulation compared to their on-PPI GERD-HRQL at baseline (9.0 vs. 2.0; p < 0.001). There were no unanticipated implantation- or stimulation-related adverse events or untoward sensation due to stimulation. There were no reports of treatment-related dysphagia, and manometric swallow was also unaffected. CONCLUSIONS: Electrical stimulation of the LES is safe and effective for treating GERD. There is a significant and sustained improvement in GERD symptoms, esophageal pH, and reduction in PPI usage without any side effects with the therapy. Furthermore, the therapy can be optimized to address an individual patient's disease.

Stauffer's syndrome with jaundice, a paraneoplastic manifestation of renal cell carcinoma: a case report.

OBJECTIVE: To report an infrequent case of Stauffer's Syndrome with jaundice as a paraneoplastic syndrome of a metastatic renal cancer. METHODS: We describe the set up of cholestatic jaundice without neoplastic liver infiltration in a patient with a metastatic renal cell carcinoma, which turned back with surgery and systemic treatment. RESULTS: Proper treatment of baseline disease enables turn back paraneoplastic signs and symptoms of Stauffer's Syndrome. CONCLUSIONS: Reversible cholestatic jaundice without evidence of hepatic disease is an infrequent form of the Stauffer's syndrome. This paraneoplastic syndrome is associated particularly with renal carcinoma but was described in lymphoproliferative diseases, prostate cancer and broncogenic tumors. This paraneoplastic entity is characterized by elevated alkaline phosphatase, erythrocyte sedimentation rate and gamma-glutamyl transferase without liver neoplastic infiltration.

Síndrome de Stauffer con ictericia, una manifestación paraneoplásica del carcinoma renal: a propósito de un caso / Stauffer’s Syndrome with jaundice, a paraneoplastic manifestation of renal cell carcinoma: a case report

OBJETIVO: Presentar un caso infrecuente de sindrome de Stauffer con ictericia como sindrome paraneoplásico de un cáncer renal metastático.MÉTODOS: Describimos la instalación de un cuadro de ictericia colestásica sin infiltración hepática en un paciente con carcinoma metastático de células renales, que revirtió con cirugía y tratamiento sistémico.RESULTADOS: El tratamiento de la enfermedad de base revierte la signo-sintomatología del cuadro paraneoplásico característico del sindrome de Stauffer. CONCLUSIONES: La ictericia colestática reversible sin evidencia de enfermedad hepática es una variante infrecuente del sindrome de Stauffer. Este sindrome paraneoplásico está asociado particularmente con el carcinoma de células renales pero también ha sido hallado acompañando a enfermedades linfoproliferativas, cánceres de próstata y tumores broncogénicos.Se caracteriza por elevación de la fosfatasa alcalina, la eritrosedimentación y la gamma glutamil transferasa sin infiltración neoplásica del hígado(AU)

OBJECTIVE: To report an infrequent case of Stauffer’s Syndrome with jaundice as a paraneoplastic syndrome of a metastatic renal cancer.METHODS: We describe the set up of cholestatic jaundice without neoplastic liver infiltration in a patient with a metastatic renal cell carcinoma, which turned back with surgery and systemic treatment.RESULTS: Proper treatment of baseline disease enables turn back paraneoplastic signs and symptoms of Stauffer’s Syndrome.CONCLUSIONS: Reversible cholestatic jaundice without evidence of hepatic disease is an infrequent form of the Stauffer’s syndrome. This paraneoplastic syndrome is associated particularly with renal carcinoma but was described in lymphoproliferative diseases, prostate cancer and broncogenic tumors.This paraneoplastic entity is characterized by elevated alkaline phosphatase, erythrocyte sedimentation rate and gamma-glutamyl transferase without liver neoplastic infiltration(AU)

Genetic dissection of Verticillium wilt resistance mediated by tomato Ve1.

Vascular wilt diseases caused by soil-borne pathogens are among the most devastating plant diseases worldwide. The Verticillium genus includes vascular wilt pathogens with a wide host range. Although V. longisporum infects various hosts belonging to the Cruciferaceae, V. dahliae and V. albo-atrum cause vascular wilt diseases in over 200 dicotyledonous species, including economically important crops. A locus responsible for resistance against race 1 strains of V. dahliae and V. albo-atrum has been cloned from tomato (Solanum lycopersicum) only. This locus, known as Ve, comprises two closely linked inversely oriented genes, Ve1 and Ve2, that encode cell surface receptor proteins of the extracellular leucine-rich repeat receptor-like protein class of disease resistance proteins. Here, we show that Ve1, but not Ve2, provides resistance in tomato against race 1 strains of V. dahliae and V. albo-atrum and not against race 2 strains. Using virus-induced gene silencing in tomato, the signaling cascade downstream of Ve1 is shown to require both EDS1 and NDR1. In addition, NRC1, ACIF, MEK2, and SERK3/BAK1 also act as positive regulators of Ve1 in tomato. In conclusion, Ve1-mediated resistance signaling only partially overlaps with signaling mediated by Cf proteins, type members of the receptor-like protein class of resistance proteins.