Relationship of sliding hiatus hernia to gastroesophageal reflux disease: a possible role for Helicobacter pylori infection?

Sliding hiatal hernia is a common endoscopic finding with a prevalence that increases with the age of patients. Although nearly all patients with GERD have HH, only a minority of patients with hernia reports reflux symptoms. Our hypothesis is that H. pylori infection may be responsible for the high number of asymptomatic hernias. After exclusion of patients with peptic ulcer, 507 patients with an endoscopic diagnosis of hernia were considered. Patients were divided into three groups: A, 45 years, 141 patients; B, 46–60 years, 144 patients; and C, 61 years, 222 patients. Presence of reflux symptoms (questionnaire) and esophagitis, H. pylori status, and gastric histology were recorded. The prevalence of hernia in the total series was 11% in group A, 23% in B, and 38% in C. Aging was associated with a significant increase in H. pylori prevalence and corpus gastritis scores, and a parallel decrease of GERD symptom prevalence, which was 66.6% in group A, 52.1% in B, and 46.8% in C (P < 0.01). Taking the three groups together, prevalence of H. pylori infection was higher in patients without GERD than with GERD (66.4 vs 57.3%, P < 0.05), and higher in patients with nonerosive GERD than erosive GERD (62.8 vs 48.6%, P = 0.02); corpus gastritis scores were significantly higher in patients without GERD than those with GERD and in those with nonerosive than erosive GERD. In conclusion, H. pylori infection protects against development of GERD in subjects with hiatus hernia. This effect is significantly more evident in the elderly where, in spite of the high prevalence of hernia, only a small number of individuals develop GERD. The development of a corpus-predominant gastritis is probably responsible for this effect.     

Nebivolol improves coronary flow reserve in hypertensive patients without coronary heart disease

OBJECTIVE: To examine the effects of nebivolol, a beta-blocker with nitroxide-mediated vasodilating properties, on coronary flow reserve (CFR) in patients with uncomplicated arterial hypertension. DESIGN, SETTING AND PATIENTS: Fourteen newly diagnosed, never-treated, World Health Organization grade I-II hypertensive patients (male/female, 10/4; mean age, 47 years), free of coronary heart disease, underwent standard Doppler echocardiography and determination of CFR in the distal left anterior descending artery by low-dose dipyridamole (0.56 mg/kg intravenously in 4 min) at baseline and after 4 weeks of treatment with 5 mg nebivolol once daily. RESULTS: At baseline, nine patients had left ventricular (LV) hypertrophy (LV mass index > or = 51 g/m). After 4 weeks of therapy, the blood pressure was decreased from 148 +/- 8.1/101.4 +/- 4.6 mmHg to 140.7 +/- 7.0/91.1 +/- 7.4 mmHg and end-systolic stress was also significantly reduced. Heart rate was reduced (P <0.01), whereas LV end-diastolic diameter and stroke volume tended to increase (P=0.07 and P=0.09, respectively). No changes were detected in the LV mass index, relative wall thickness, fractional shortening and LV diastolic properties. Both resting and dipyridamole rate-pressure products were lower after nebivolol but dipyridamole-induced changes were not influenced by the therapy. In contrast, nebivolol therapy did not alter coronary velocities at rest, but caused a greater increase in coronary velocities after dipyridamole (P <0.03), leading to a greater CFR (2.12 +/- 0.33 versus 1.89 +/- 0.31, P <0.0001). Nebivolol induced an absolute increase of 8% in the CFR in nine of 14 patients (64.3%). CONCLUSIONS: In hypertensive patients free of coronary artery disease, 4-week nebivolol therapy induces a significant increase of the CFR. Nebivolol preserves coronary flow at rest despite the reduction of metabolic (O2 consumption) and hemodynamic (diastolic blood pressure) determinants. The increase of hyperemic coronary velocities appears due to the reduction of coronary resistance.     

Molecular histogenesis of posttransplantation lymphoproliferative disorders

Posttransplantation lymphoproliferative disorders (PTLDs) represent a serious complication of solid organ transplantation. This study assessed the molecular histogenesis of 52 B-cell monoclonal PTLDs, including 12 polymorphic PTLDs (P-PTLDs), 36 diffuse large B-cell lymphomas (DLBCLs), and 4 Burkitt/Burkitt-like lymphomas (BL/BLLs). Somatic hypermutation (SHM) of immunoglobulin variable (IgV) genes documented that most monoclonal B-cell PTLDs (75% P-PTLDs, 91.3% DLBCLs, 100% BL/BLLs) derive from germinal center (GC)-experienced B cells. B-cell lymphoma 6 (BCL6) mutations occurred in 25% P-PTLDs, 60.6% DLBCLs, and 75.0% BL/BLLs. A first histogenetic category of PTLDs (31.2% DLBCLs) express the BCL6+/multiple myeloma oncogene-1 protein (MUM1-/+)/CD138- profile and mimic B cells experiencing the GC reaction, as also suggested by ongoing SHM in a fraction of these cases. A second subset of PTLDs (66.7% P-PTLDs and 31.2% DLBCLs) display the BCL6-/MUM1+/CD138- phenotype and mimic B cells that have concluded the GC reaction. A third histogenetic category of PTLDs (25.0% P-PTLDs and 31.2% DLBCLs) shows the BCL6-/MUM1+/CD138+ profile, consistent with preterminally differentiated post-GC B cells. Crippling mutations of IgV heavy chain (IgVH) and/or IgV light chain (IgVL) genes, leading to sterile rearrangements and normally preventing cell survival, occur in 4 DLBCLs and 1 BL/BLL that may have been rescued from apoptosis through expression of Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1). Overall, the histogenetic diversity of monoclonal B-cell PTLDs may help define biologically homogeneous categories of the disease.     

Non-alcoholic acute Wernicke's encephalopathy: Role of MRI in non typical cases

Aim

Acute Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency, most commonly found in chronic alcoholics. It is not so easy to suspect acute WE when the clinical picture does not include all the typical symptoms and alcohol abuse is not reported. Three rare cases of Wernicke's encephalopathy (WE) in non-alcoholic patients are reported.

Cases presentation

Two patients developed the disease following prolonged intravenous feeding, the third was carrying a gastric lymphoma. None of them presented with the classic clinical triad of WE (ophtalmoplegia/nystagmus, ataxia and consciousness disturbance), showing just one or two of the typical symptoms. Brain Magnetic Resonance Imaging (MRI) represented the key tool to suspect and define WE diagnosis, showing a picture characterized by bilaterally altered signal of the thalamic pulvinar, mesencephalic cup, mammillary bodies, periaqueductal grey matter and floor of fourth ventricle. All patients dramatically improved within 48 h after administration of thiamine.

Conclusion

We emphasize that WE should be suspected in all patients showing typical MRI features presenting with at least one of the clinical triad of WE.     

Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: Sentinel node vs Observation after axillary UltraSouND)

Sentinel lymph node biopsy (SLNB) is the standard approach for axillary staging in patients with early breast cancer. Recent data showed no outcome difference in patients with positive sentinel node between axillary dissection vs no further axillary surgery, raising doubts on the role of SLNB itself. Therefore, a new trial was designed comparing SLNB vs observation when axillary ultra-sound is negative in patients with small breast cancer candidates to breast conserving surgery.     

Effect of food restriction on ghrelin in normal-cycling female rats and in pregnancy

OBJECTIVE: Ghrelin is a 28-amino-acid acylated peptide that was recently identified as the endogenous ligand for the growth hormone secretagogue receptor. Previous studies have shown that ghrelin potently increases growth hormone release and food intake. The aim of this study was to clarify the physiological implications of ghrelin in the regulation of energy balance, by assessing the effect of undernutrition throughout 21 days in normal-cycling and pregnant rats on ghrelin. RESEARCH METHODS AND PROCEDURES: We have determined ghrelin levels by radioimmunoassay and gastric ghrelin mRNA expression by Northern blot analysis during 21 days of chronic food restriction (30% of ad libitum available diet) in normal-cycling female rats and in pregnancy. RESULTS: Our results show that chronic food restriction led to an increase in plasmatic ghrelin levels in normal-cycling female rats. In pregnancy, ghrelin plasmatic levels were enhanced particularly during the latter part of gestation (19 and 21 days) compared with pregnant rats with free access to food. Gastric ghrelin mRNA expression showed a similar expression pattern, being higher in the food-restricted group than in the group fed ad libitum, in normal-cycling as well as in pregnant rats. DISCUSSION: These observations indicate that ghrelin plasmatic levels and ghrelin gastric mRNA are up-modulated during undernutrition in normal-cycling rats and in pregnancy. These findings suggest that increased ghrelin levels may have a role in mediating the physiological responses to undernutrition and could represent an adaptative response to prevent long-lasting alterations in energy balance and body weight homeostasis.     

Mucormycosis in hematologic malignancies: an emerging fungal infection

BACKGROUND AND OBJECTIVES. In recent years pulmonary mucormycosis has been reported in patients with leukemia and lymphoma and bone marrow transplant recipients. It carries an extremely poor prognosis. We report our experience of clinical findings, diagnostic procedures, treatment and outcome of mucormycosis diagnosed in neutropenic patients affected by hematologic neoplasms admitted to our Department. DESIGN AND METHODS. From November 1987 to July 1999 we observed 13 cases of Mucor. Their median age was 61 years (range 20-75), and they were predominantly in the aplastic post-chemotherapy period (12/13), affected by acute myeloid leukemia (11 cases ) or non-Hodgkin's lymphoma (2 cases). Six patients (all with leukemia) were receiving inductionEth consolidation therapy, 7 had progressive hematologic disease. At the onset of infection all patients were neutropenic (N < 0.5x10(9)/L). No patients had diabetes mellitus. Two patients had been receiving steroid therapy for 5 and 7 days. RESULTS. The lung was involved in all cases (13/13); disseminated disease was present in 8/13 patients. All cultures (blood, sputum, nasal swabs and bronchoalveolar lavage) were negative. In 3 patients a histologic diagnosis was made in vivo: in 1 patient by percutaneous pulmonary biopsy, in 1 patient by pulmonary lobectomy, and in the last patient by percutaneous pulmonary biopsy confirmed by excision of a cerebellar abscess. In the remaining 10 cases diagnosis was made post-mortem. Five patients were not treated, 2 because of poor clinical condition and 3 because fungal infection was not suspected. Amphotericin B (1 mg/kg/day) was given empirically to 6 patients and 2 responded to treatment. The remaining 2 patients with neurologic symptoms at the onset of infection were treated with liposomal amphotericin, Ambisome, one with 3 and one with 5 mg/kg/day; of these two patients the first died in 4 days; the second, with both pulmonary and cerebellar localizations, was treated successfully with 5 mg/kg/day for 4 weeks and then with 3 mg/kg/day, and excision of a brain abscess at neutrophil recovery (total dose of Ambisome: 12,000 mg). The 3 surviving leukemic patients were able to complete subsequent consolidation therapy using amphotericin B or liposomal amphotericin as secondary prophylaxis during aplasia. INTERPRETATION AND CONCLUSIONS. In neutropenic hematologic patients Mucor is rarely suspected. In our patients infection was often characterized by disseminated disease and a rapidly fatal course; only early aggressive amphotericin B (or Ambisome) treatment together with neutrophil recovery appeared to improve the outcome. Diagnosis is very important for programming antifungal therapy and secondary prophylaxis with amphotericin B, because Mucor is usually resistant to itraconazole.     

Antibiotic prophylaxis in head and neck cancer surgery: Systematic review and Bayesian network meta-analysis

Postoperative surgical site infections (SSI) are worrisome complications after head and neck cancer surgery. Due to the lack of direct comparisons, it is difficult to indicate the best antibiotic in the setting of SSI prophylaxis for patients with head and neck cancer. For this reason, we decided to conduct a Bayesian network meta-analysis of clinical studies evaluating various antibiotic classes for SSI prophylaxis; thus, we directly and indirectly compared all the available antibiotics in the setting of head and neck oncological surgery. We performed a systematic review and a network meta-analysis according to the PRISMA-NMA checklist. Regarding inclusion criteria, we included articles with retrospective or prospective design recruiting adult participants with head and neck neoplasm of any subsite that compared different antibiotics or that compared different antibiotic treatment duration with sample sizes of more than 10 patients. Overall, 310 citations were identified by the search on all databases. Of these, 250 were excluded based on title and abstract, leaving 60 publications for full text examination. Finally, 20 papers were included for data extraction and analysis. In total, 8627 patients were evaluated across the included studies. Results of the Bayesian network meta-analysis showed that when compared to clindamycin short course, the antibiotics effective in preventing SSI were ampicillin/sulbactam or other penicillin short course (OR: 0.37, 95%CrI: 0.19–0.72), cefazolin/metronidazole short course (OR: 0.26, 95%CrI: 0.06–0.93), cefazolin (OR: 0.36, 95%CrI: 0.17–0.79), ampicillin/sulbactam long course (OR: 0.20, 95%CrI: 0.04–0.91), cefazolin/metronidazole long course (OR: 0.27, 95%CrI: 0.09–0.64), cefoperazone (OR: 0.05, 95%CrI: 0.002–0.89), cefotaxime (OR: 0.04, 95%CrI: 0.002–0.85). There was no significant difference between clindamycin and no antibiotic (OR: 2.3, 95%CrI: 0.59–9.9). Clindamycin plus aminoglycoside seemed to give a slight protection from SSI compared to clindamycin alone (OR: 0.30, 95%CrI: 0.09–0.99) or no antibiotic (OR: 0.13, 95%CrI: 0.02–067). Antibiotic prophylaxis is important in preventing SSI in head and neck cancer setting. Current evidence suggests that penicillins and cephalosporins are the best choice. Moreover, long duration course does not give any advantage compared to short course prophylaxis. Finally, it is important to implement appropriate antibiotic prophylaxis in patients that are labeled as penicillin allergic, in this regard clindamycin seems to be ineffective and, for this reason, further research is needed to provide a better care for this subset of patients.