Cerebrospinal Fluid Aβ42 Levels: When Physiological Become Pathological State

Impaired amyloid beta (Aβ) metabolism is currently considered central to understand the pathophysiology of Alzheimer's disease (AD). Measurements of cerebrospinal fluid Aβ levels remain the most useful marker for diagnostic purposes and to individuate people at risk for AD. Despite recent advances criticized the direct role in neurodegeneration of cortical neurons, Aβ is considered responsible for synaptopathy and impairment of neurotransmission and therefore remains the major trigger of AD and future pharmacological treatment remain Aβ oriented. However, experimental and clinical findings showed that Aβ peptides could have a wider range of action responsible for cell dysfunction and for appearance of clinico‐pathological entities different from AD. Such findings may induce misunderstanding of the real role played by Aβ in AD and therefore strengthen criticism on its centrality and need for CSF measurements. Aim of this review is to discuss the role of CSF Aβ levels in light of experimental, clinical pathologic, and electrophysiological results in AD and other pathological entities to put in a correct frame the value of Aβ changes.     

Brentuximab vedotin as salvage treatment in Hodgkin lymphoma naïve transplant patients or failing ASCT: the real life experience of Rete Ematologica Pugliese (REP)

Brentuximab vedotin (BV) shows a high overall response rate (ORR) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous transplant (ASCT). The aim of this multicenter study, conducted in nine Hematology Departments of Rete Ematologica Pugliese, was to retrospectively evaluate the efficacy and safety of BV as salvage therapy and as bridge regimen to ASCT or allogeneic transplant (alloSCT) in R/R HL patients. Seventy patients received BV. Forty-five patients (64%) were treated with BV as bridge to transplant:16 (23%) patients as bridge to ASCT and 29 (41%) as bridge to alloSCT. Twenty-five patients (36%), not eligible for transplant, received BV as salvage treatment. The ORR was 59% (CR 26%). The ORR in transplant naïve patients was 75% (CR 31%). In patients treated with BV as bridge to alloSCT, the ORR was 62% (CR 24%). In a multivariate analysis, the ORR was lower in refractory patients (p?<?0.005). The 2y-OS was 70%. The median PFS was 17 months. Ten of the 16 (63%) naïve-transplant patients received ASCT, with 50% in CR before ASCT. In the 29 patients treated with BV as bridge to alloSCT, 28 (97%) proceeded to alloSCT with 25% in CR prior to alloSCT. The most common adverse events were peripheral neuropathy (50%), neutropenia (29%) and anemia (12%). These data suggest that BV is well tolerated and very effective in R/R HL, producing a substantial level of CR. BV may also be a key therapeutic agent to achieve good disease control before transplant, improving post- transplant outcomes, also in refractory and heavily pretreated patients, without significant overlapping toxicities with prior therapies.     

Treatment of PPI-resistant gastro-oesophageal reflux: A systematic review

Background and study aims

Several studies have demonstrated the superiority of proton-pump inhibitors (PPIs) in resolving erosive gastro-oesophageal reflux disease (GORD). However, this first line of treatment can fail to control symptoms in around 30% of cases, especially in the presence of non-erosive GORD. In situations where the first line of treatment fails, there is a lack of concordance regarding the best strategy to apply. This study presents a systematic review of the trials which have tested second-line treatments after PPI failure.

Propafenone versus procainamide for conversion of atrial fibrillation to sinus rhythm

Background and hypothesis: Antiarrhythmic drugs are widely used for treatment of atrial fibrillation (AF) and restoration off sinus rhythm. This prospective, randomized, and controlled study compared the efficiency and safety of propafenone versus procainamide for the treatment of acute AF. Methods: In all, 117 patients (55 women, 62 men, mean age 64.2 ± 13 years, median 63 years) who presented with AF were included in the study. Exclusion criteria were signs or symptoms of heart failure on physical examination, recent myocardial infarction or cardiac surgery, cardiogenic shock, or hypotension. Forty-one patients spontaneously recovered sinus rhythm; the remaining 76 patients were randomized to receive propafenone or procainamide. Propafenone was given at a dose of 2 mg/kg body weight intravenously (IV) over 30 min. Patients randomized to receive procainamide received a bolus of 100 mg IV administered every 5 min up to a maximum dose of 1 g. The clinical characteristics of the two groups were comparable. Results: The number of patients who recovered sinus rhythm after the treatment was larger in the procainamide-treated group (Group 1) (69.5%) than in the propafenone-treated group (Group 2) (48.7%); p < 0.05. The time required for cardioversion was significantly lower in Group 1 (mean 4.1 ± 1.3 h). than in Group 2 patients (mean 7.3 ± 2.6 h) (p<0.01). Conclusion: In the present study, procainamide was more effective than propafenone for the treatment of AF of short duration.     

Laparoscopic management of intra-abdominal infections: Systematic review of the literature

AIM: To investigate the role of laparoscopy in diagnosis and treatment of intra abdominal infections.METHODS: A systematic review of the literature was performed including studies where intra abdominal infections were treated laparoscopically.RESULTS: Early laparoscopic approaches have become the standard surgical technique for treating acute cholecystitis. The laparoscopic appendectomy has been demonstrated to be superior to open surgery in acute appendicitis. In the event of diverticulitis, laparoscopic resections have proven to be safe and effective procedures for experienced laparoscopic surgeons and may be performed without adversely affecting morbidity and mortality rates. However laparoscopic resection has not been accepted by the medical community as the primary treatment of choice. In high-risk patients, laparoscopic approach may be used for exploration or peritoneal lavage and drainage. The successful laparoscopic repair of perforated peptic ulcers for experienced surgeons, is demonstrated to be safe and effective. Regarding small bowel perforations, comparative studies contrasting open and laparoscopic surgeries have not yet been conducted. Successful laparoscopic resections addressing iatrogenic colonic perforation have been reported despite a lack of literature-based evidence supporting such procedures. In post-operative infections, laparoscopic approaches may be useful in preventing diagnostic delay and controlling the source.CONCLUSION: Laparoscopy has a good diagnostic accuracy and enables to better identify the causative pathology; laparoscopy may be recommended for the treatment of many intra-abdominal infections.     

Improved local control and survival with the “sandwich” technique of pelvic radiotherapy for resectable rectal cancer A retrospective, multivariate analysis

PURPOSE: The following study was done to evaluate the therapeutic value of radiotherapy as an adjunct to surgery for rectal cancer patients. METHODS: One-hundred twenty-four patients underwent curative resection by one surgeon (RC) from 1982 to 1991. Forty patients received combined preoperative and postoperative (sandwich) radiotherapy, 30 patients received postoperative radiotherapy, and 54 patients were treated by surgery alone. During the study period sandwich radiotherapy was primarily offered as a free treatment option for patients with tumors which were believed to be transmurally invasive, whereas postoperative radiotherapy was an alternative therapeutic option offered to patients with tumor classified as Dukes B and C at histopathologic examination. RESULTS: Operative mortality was 2 percent in the sandwich radiotherapy group vs. 7 percent in the surgery alone group. After a median follow-up of 60 months, the actuarial locoregional recurrence rate at five years was 3 percent for the sandwich radiotherapy group compared with 18 and 30 percent for the postoperative radiotherapy and surgery alone groups, respectively (P =0.019). A multivariate analysis using the Cox model confirmed the favorable independent influence of sandwich radiotherapy on local tumor control, especially in distal tumors. The therapeutic benefit of sandwich radiotherapy translated into increased survival in the low-rectum Dukes B subgroup of patients. The actuarial five-year survival rates were 86 percent, 50 percent, and 28 percent in the sandwich radiotherapy, postoperative radiotherapy and surgery alone groups, respectively (P =0.05). CONCLUSIONS: Preoperative radiotherapy has a significant effect on the prognosis of rectal cancer patients.     

Colorectal cancer screening: The surgery rates they are a-changing. A nationwide study on surgical resections in Italy

Background

Growing evidence suggests that colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) reduces CRC incidence and surgical resection rates.