Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells

Tumor-promoted constraints negatively affect cytotoxic T lymphocyte (CTL) trafficking to the tumor core and, as a result, inhibit tumor killing. The production of reactive nitrogen species (RNS) within the tumor microenvironment has been reported in mouse and human cancers. We describe a novel RNS-dependent posttranslational modification of chemokines that has a profound impact on leukocyte recruitment to mouse and human tumors. Intratumoral RNS production induces CCL2 chemokine nitration and hinders T cell infiltration, resulting in the trapping of tumor-specific T cells in the stroma that surrounds cancer cells. Preconditioning of the tumor microenvironment with novel drugs that inhibit CCL2 modification facilitates CTL invasion of the tumor, suggesting that these drugs may be effective in cancer immunotherapy. Our results unveil an unexpected mechanism of tumor evasion and introduce new avenues for cancer immunotherapy

Modified balloon aortic valvuloplasty in fragile symptomatic patients unsuitable for both surgical and percutaneous valve replacement

BACKGROUND: Balloon Aortic valvuloplasty (BAV) is considered as a bridge therapy to percutaneous valve implantation or a palliative treatment in patients with aortic valve stenosis (AVS). Potential risk of complications, in particular in fragile patients, is still not negligible. AIM: To describe the technique and outcomes of modified BAV in fragile symptomatic patients unsuitable for other treatments using no-pacing and minimally invasive approach. METHODS: Symptomatic fragile patients with severe aortic valve stenosis judged unsuitable by the heart team for surgical or percutaneous valve implantation from 1 September 2013 to 1 September 2017 were offered modified BAV. Simplified procedural protocol included a 4F right radial artery access for gradient check, a 8F compatible undersized balloons, two partial inflations-trial before a full inflation with no-pace maker back-up, final pressure gradient recording and aortography. RESULTS: Thirty-four symptomatic fragile patients (mean age 80.9\ub14.9, range 73 to 91years, 100% Katz >6, mean Euroscore I 30.0\ub111.7%) underwent modified BAV in the last 5years with immediate success in all (100%). Mean aortic valve area increased from 0.58\ub10.2cm2 to 1.1\ub10.2cm2 (p<0.01) whereas mean peak gradient decreased from 75.6\ub111.3 to 35.8\ub111.2mmHg (p<0.01). Procedural complications were 14.7%. Thirty-day mortality was 11.8%. On a mean follow up of 38.4\ub14.6months four patients successfully repeated the procedure, while global mortality was 23.5% (8 patients). The other 22 patients maintained a NYHA class of 2.1\ub10.7. CONCLUSIONS: No-pacing minimally invasive BAV seems to have acceptable outcomes in patients with severe AVS and no other treatment options

Effects of nizatidine on gastric acid and bicarbonate secretion

The effects of nizatidine on human gastric parietal secretion (volume and acid output) and nonparietal secretion (volume and bicarbonate concentration and secretion) were evaluated in 18 patients with duodenal ulcer. Nizatidine reduced the volume of pentagastrin-stimulated gastric secretion and gastric acid secretion. Nizatidine also decreased the volume of nonparietal secretion and bicarbonate secretion, although bicarbonate concentration remained unchanged. © 1993 Excerpta Medica, Inc. All rights reserved

Do concomitant diseases and therapies affect the persistence of ulcer symptoms in the elderly?

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study; 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size

Pediatric Sleep Questionnaire Predicts Moderate-to-Severe Obstructive Sleep Apnea in Children and Adolescents with Obesity

Pediatric obesity is associated with an increased risk of morbidity during childhood. Alongside the well-known metabolic syndrome, during the last decades scientific research has deeply investigated the risk of sleep breathing disorders. Among them, obstructive sleep apnea (OSA) commonly affects children with obesity. The presence of OSA heightens the risk of metabolic impairment and weight gain. Therefore, it deserves specific treatment. However, polysomnography (PSG) is not always available in clinical settings, and alternative diagnostic tools are needed. This study aimed to investigate the predictivity of the pediatric sleep questionnaire (PSQ) for moderate-to-severe OSA diagnosis. Children and adolescents with obesity and suspected OSA with available full-night cardiorespiratory PSG were retrospectively enrolled. Receiver operating curve analysis was performed to test the ability of PSQ in predicting moderate-to-severe OSA (AHI > 5 episode/h). The final sample included 60 children and adolescents. The PSQ showed a good area under the curve (AUC) of 0.88 (95% CI 0.78-0.98, p < 0.0001). Moreover, a value above or equal to 0.65 showed an 80% sensitivity and 100% specificity for moderate and severe OSA. These findings suggest that PSQ might be used in clinical settings with limited access to PSG for stratifying disease severity and for selecting children with urgent need of sleep study