Kniearthrodesen

When arthrodesis of the knee is indicated, the operative procedure selected for fixation depends on the condition of the soft tissues, the bone stock, whether infection is present, and the age of the patient and his or her capacity for partial weight-bearing. In young patients with no infection or soft tissue problems, when adequate bone stock is present compression plating or the use of an intramedullary nail is possible and allows stable fixation. Soft tissue problems with defect(s) or infection are a good indication for the use of an external fixator. The most common indication for knee arthrodesis is a failed total knee prosthesis that has become infected. Deficient bone stock with osteopenic bone or a defect after failed total knee arthroplasty are problems that can be solved by the use of modular fusion nail systems, especially in older patients. These systems are more comfortable for the patient than external fixation devices and allow early full weight-bearing.     

Risk of thromboembolic complications in patients with permanent atrial fibrillation undergoing cardioverter-defibrillator implantation

BACKGROUND: Cardioversion of atrial fibrillation (AF) carries the risk of thromboembolic complications and, therefore, anticoagulation therapy is routinely administered before and after this procedure. In patients with permanent AF who undergo implantation of cardioverter-defibrillator (ICD), anticoagulants are usually withdrawn during the perioperative period. However, in some patients sinus rhythm may be restored during defibrillation threshold (DFT) testing which potentially may increase the risk of thromboembolic complications. AIM: To assess the frequency of sinus rhythm restoration during ICD implantation in patients with permanent AF and the rate of both thromboembolic events and local bleeding complications which may occur due to temporary withdrawal of anticoagulation therapy and its re-initiation early after the procedure. METHODS: Permanent AF was present in 23 (12%) of 193 patients selected for ICD implantation. All patients received prolonged oral anticoagulation according to the generally accepted standards. Anticoagulation therapy was stopped few days before the procedure and replaced by low molecular weight heparin which was administered up to 24 hours before ICD implantation and re-initiated 12-24 hours afterwards. RESULTS: During DFT testing sinus rhythm was restored in 5 (21.7%) patients with AF. Clinical and DFT characteristics were similar in those who were converted to sinus rhythm and those who remained in AF. No thromboembolic events were noted in either group. Local haematoma at the site of ICD implantation occurred in two (8%) patients. CONCLUSIONS: Sinus rhythm was restored in 21.7% of patients with permanent AF who underwent ICD implantation. Temporary withdrawal of anticoagulation therapy did not increase the risk of thromboembolic complications, however, its early re-initiation after implantation resulted in an increase in local bleeding complication rate.     

Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial

Aims

The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population.

Methods and results

161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n = 50, 20 mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n = 56, 5 mg/h and 5 μg kg^− 1 min^− 1 respectively), or c) low-dose furosemide (LDF, n = 55, furosemide 5 mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3 mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24 h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P = 0.74) or at one year (38.1%, 33.9% and 32.7%, P = 0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P = 0.55) or one year (60.0%, 50.0%, and 47%, P = 0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P < 0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P = 0.27). No significant differences in adverse events were noted.

Conclusions

In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

A long-term trend and temporal fluctuations of the sea level at the Polish Baltic coast

The analysis of sea level record series along the Polish coast is presented. The main aim was to identify linear trends in the sea level changes at the coastal (?winouj?cie, Ko?obrzeg, Ustka, ?eba, W?adys?awowo, Hel, Gdynia, Gdańsk), lagoonal (Trzebie?, Tokmicko) and riverine (Szczecin) gauge stations. The analysis showed individual coastal stations to differ in the rate of sea level changes. During 60 years of continuous observations (1947–2006), the differences varied from 1.0 (the western part of the coast) to 2.5 mm year^?1 (the eastern part of the coast). The longest, more than 100-yr-long data series showed the sea level rise in ?winouj?cie and Ko?obrzeg to be about 0.5 mm year^?1; 1.57 mm year^?1 being revealed in Gdańsk. Spectral analysis applied to the data showed numerous fluctuations and cyclicity in changes of the annual mean sea level at the Polish coast. A distinct, major 3-year cycle was revealed. In addition, three secondary cycles of 4.6, 6.7, and 8.6 years were present in the data, more or less clearly identifiable at individual stations.