Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Therapeutic option for managing lung injury induced by infrarenal aortic cross-clamping

Background

Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem.

Objectives

Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning.

Materials and methods

Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated.

Results

Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO₂ level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05).

Conclusions

Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.     

Electron and High-Dose-Rate Brachytherapy Boost in the Conservative Treatment of Stage I–II Breast Cancer

BACKGROUND AND AIMS: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. PATIENTS AND METHODS: 207 women with stage I-II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n = 104) or no further radiotherapy (n = 103). Boost treatments consisted of either 16 Gy electron irradiation (n = 52) or 12-14,25 Gy HDR BT (n = 52). Breast cancer-related events, side effects, and cosmetic results were assessed. RESULTS: At a median follow-up of 5.3 years, the crude rate of local recurrences was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs. 84.9% (p = 0.049), 76.6% vs. 66.2% (p = 0.044), and 90.4% vs. 82.1% (p = 0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs. 91.4%; p = 0.74). On multivariate analysis, patient age < 40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2-3 side effects was higher in the boost arm (17.3% vs. 7.8%; p = 0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p = 0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p = 0.29). CONCLUSIONS: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age should be viewed as absolute indications for tumor bed boost. LTC and cosmesis are excellent and similar to patients boosted with either HDR BT or electrons.     

Electron and High-Dose-Rate Brachytherapy Boost in the Conservative Treatment of Stage I-II Breast Cancer First Results of the Randomized Budapest Boost Trial

Background and Aims: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. Patients and Methods: 207 women with stage I-II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n = 104) or no further radiotherapy (n = 103). Boost treatments consisted of either 16 Gy electron irradiation (n = 52) or 12-14,25 Gy HDR BT (n = 52). Breast cancer-related events, side effects, and cosmetic results were assessed. Results: At a median follow-up of 5.3 years, the crude rate of local recurrences was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs. 84.9% (p = 0.049), 76.6% vs. 66.2% (p = 0.044), and 90.4% vs. 82.1% (p = 0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs. 91.4%; p = 0.74). On multivariate analysis, patient age < 40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2-3 side effects was higher in the boost arm (17.3% vs. 7.8%; p = 0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p = 0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p = 0.29). Conclusions: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age should be viewed as absolute indications for tumor bed boost. LTC and cosmesis are excellent and similar to patients boosted with either HDR BT or electrons. Hintergrund und Ziel: In einer prospektiv randomisierten Studie werden die Effekte eines Elektronenboosts und eines High-Dose-Rate-Brachytherapie-(HDR-BT-)Boosts bezüglich lokaler Tumorkontrolle (LTC), Nebenwirkungen und kosmetischer Ergebnisse nach brusterhaltender Operation (BCS) evaluiert. Patienten und Methodik: 207 Patientinnen mit Brustkarzinomen im Stadium I-II wurden einer BCS zugeführt. Postoperativ erfolgte eine perkutane Radiatio der gesamten Brust bis 50 Gy. Daran schloss sich willkürlich entweder eine Boostbestrahlung des Tumorbetts (n = 104) oder keine weitere Radiatio (n = 103) an. Die Boostbestrahlung erfolgte perkutan mit 16 Gy Elektronen (n = 52) oder in Form einer HDR-BT mit 12-14,25 By (n = 52). Untersucht wurden LTC, Nebenwirkungen und kosmetische Ergebnisse. Ergebnisse: Die mediane Nachbeobachtungszeit betrug 5,3 Jahre. Die Lokalrezidivrate lag mit Boostbestrahlung bei 6,7% (7/104), ohne Boost bei 15,5% (16/103). Die 5-Jahres-Überlebensrate für LTC, für die rezidivfreie Überlebenszeit (RFS) und für die krebsspezifische Überlebenszeit (CSS) betrugen 92,7% vs. 84,9% (p = 0,049), 76,6% vs. 66,2% (p = 0,044) und 90,4% vs. 82,1% (p = 0,053). Bezüglich der LTC bestand kein signifikanter Unterschied zwischen Patienten, die mit einem Elektronen- oder HDR-BT-Boost behandelt wurden (94,2% vs. 91,4$; p = 0,74). Die multivariate Analyse zeigte, dass Faktoren wie Patientenalter > 40 Jahre (RR: 4,53), positive Resektionsränder (RR: 4,17) und ein hoher Mitoseaktivitätsindex (RR: 3.60) das Risiko eines lokalen Rezidivs signifikant erhöhen. Die Inzidenz von Nebenwirkungen Grad 2-3 war im Boost-Arm höher (17,3% vs. 7,8%; p = 0,03). Allerdings waren die sehr guten kosmetischen Ergebnisse in beiden Armen gleich (85,6% bs. 91,3%, p = 0,14). Sehr gute kosmetische Ergebnisse wurden bei 88,5% der Patientinnen mit HDR-BT-Boost und 82,7% der Patientinnen mit Elektronenboost erreicht (p = 0,29). Schlussfolgerungen: Die Boost-Dosis verbessert signifikant LTC und RFS bei Patientinnen, die einer BCS und anschließender Radiatio zugeführt wurden. Obwohl eine höhere Inzidenz an Spätnebenwirkungen im Boost-Arm gefunden wurde, wird eine Boost-Dosis für Patientinnen mit hohem Risiko für die Entwicklung eines Lokalrezidivs empfohlen. Unserer Meinung nach ist bei Faktoren wie positive Schnittränder, schmaler Sicherheitssaum, hoher Mitoseaktivitätsindex und niedriges Patientenalter, die absolute Indikation zur Boost-Bestrahlung des Tumorbetts gegeben. LTC und die kosmetischen Ergebnisse sind sehr gut und unterscheiden sich nicht in Bezug auf Elektronenboost oder HDR-BT-Boost.     

Percutaneous fixation of acetabular fractures: computer-assisted determination of safe zones, angles and lengths for screw insertion

Introduction

Percutaneous retrograde screw fixation for acetabular fractures is a demanding procedure due to the complex anatomy of the pelvis and the varying narrow safe bony corridors. Limited information is available on optimal screw placement and the geometry of safe zones for screw insertion in the pelvis.

Methods

Three-dimensional reconstructions of 50 consecutive CT scans of polytrauma patients (35 males, 15 females) were used to introduce three virtual CAD bolts (representing screws) into the anterior column (superior ramus of the pubic bone), posterior column (the ischial bone) and the supraacetabular region, as performed during percutaneous screw fixation. The three-dimensional (3D) position of these screws was evaluated with a computer software (MIMICS) after virtual optimal insertion. The 3D position, the narrowest zone and the distance to the hip joint of the two columns and the supraacetabular region were defined.

Results

The mean maximal screw length for the three virtual screws measured between 107.4 and 148?±?18.7?mm. The narrowest zone of the pelvic bone (superior pubic ramus) had a width of 9.2?±?2.4?mm. The average distances between the bolts and the hip joint were 3.9 and 19.4?±?7.4?mm. For the anterior column (superior pubic ramus) screw, the mean lateral angle to the sagittal midline plane was 39.0?±?3.2° and the mean posterior angle to the transversal midline plane was 15.1?±?4.0°. The mean supraacetabular screw angles measured 22.4?±?3.4° (medial), 35.3?±?4.6° (cranial) and the mean angles for the ischial screw were 12.0?±?5.4° (posterior) and 18.4?±?4.0° (lateral).

Conclusions

The zones for safe screw positioning are very narrow, making percutaneous screw fixation of the acetabulum a challenging procedure. The predefined angles for the most frequently positioned percutaneous screws may aid in preoperative planning, decrease operative and radiation times and help to increase safe insertion of screws.     

Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis

Background

To evaluate the haemodynamic changes induced by flow diversion treatment in cerebral aneurysms, resulting in thrombosis or persisting aneurysm patency over time.

Method

Eight patients with aneurysms at the para-ophthalmic segment of the internal carotid artery were treated by flow diversion only. The clinical follow-up ranged between 6?days and 12?months. Computational fluid dynamics (CFD) analysis of pre- and post-treatment conditions was performed in all cases. True geometric models of the flow diverter were created and placed over the neck of the aneurysms by using a virtual stent-deployment technique, and the device was simulated as a true physical barrier. Pre- and post-treatment haemodynamics were compared, including mean and maximal velocities, wall-shear stress (WSS) and intra-aneurysmal flow patterns. The CFD study results were then correlated to angiographic follow-up studies.

Results

Mean intra-aneurysmal flow velocities and WSS were significantly reduced in all aneurysms. Changes in flow patterns were recorded in only one case. Seven of eight aneurysms showed complete occlusion during the follow-up. One aneurysm remaining patent after 1?year showed no change in flow patterns. One aneurysm rupturing 5?days after treatment showed also no change in flow pattern, and no change in the maximal inflow velocity.

Conclusions

Relative flow velocity and WSS reduction in and of itself may result in aneurysm thrombosis in the majority of cases. Flow reductions under aneurysm–specific thresholds may, however, be the reason why some aneurysms remain completely or partially patent after flow diversion.     

Efficacy and safety of emergency non-invasive pelvic ring stabilisation

BackgroundUrgent non-invasive pelvic ring stabilisation (pelvic binding, PB) in shocked patients is recommended by state and institutional guidelines regardless of the fracture pattern. The purpose of this study was to determine the adherence to the guidelines, efficacy of the technique and identification of potential adverse effects associated with PB.Patients and methodsA 41-month retrospective analysis of the prospective pelvic fracture database was undertaken at a level 1 trauma centre. High-energy pelvic fractures were included in the analysis with exclusion of the A type injuries (AO/OTA classification) and patients who were dead on arrival. Collected data included patient demographics, injury severity score, fracture classification, application and timing of PB, associated injuries, physiological parameters, resuscitation fluids and outcomes. Pre and post-PB radiographs were reviewed. The potential effects of the PB on soft tissue (femoral vessel, bladder and rectal injury) complications were assessed by independent experts.Results115 patients with high-energy B and C type pelvic ring injuries were included. Thirty-six (31%) patients presented in haemorrhagic shock on arrival. A total of 43 pelvic bindings were performed, 18 of them on shocked patients. The adherence to the guidelines was 50% (18/36) overall. Analysing fracture types of shocked patients the adherence was: B1 80%, B2 20%, B3 20%, C1 66%, C2 86%, C3 33%. The alignment of the pelvis was improved or perfect on post-PB radiographs in 68% and had not changed in 21%. In some cases of B2 and B3 type injuries the PB increased the deformity after application (11%). There were 10 deaths (8.7%) in the study group, with 4 deaths attributed to acute pelvic bleeding. Two of these had PB applied and two were identified as potential for improvement. One femoral artery injury, four bladder injuries and three rectum injuries were identified in patients who had PB applied. Association between the PB and these injuries is unlikely.ConclusionThe adherence to the guidelines should be improved with further education and system development. The good effect of the technique was evident on radiographs. Although in some lateral compression fracture patterns the deformity increased, no hazards were associated with the use of PB.     

Neoadjuvant chemotherapy in advanced stomach cancer--a case of complete response

In the treatment of gastric cancer R0 surgical resection is the only hope for cure. Unfortunately most patients are first seen when they are in an advanced stage, when the possibility of R0 resection is very poor. In these cases administration of other therapies is justified. In the last decade neoadjuvant combination chemotherapy had been introduced with promising results. ECF neoadjuvant chemotherapy has 60% response rate in irresectable cases. We report about a patient with locally advanced gastric cancer treated with neoadjuvant ECF chemotherapy. The patient reacted with complete response, so following chemotherapy R0 resection could be carried out. We describe different therapies used for patients with locally advanced gastric cancer. Neoadjuvant chemotherapy is a recommended therapeutic modality in locally advanced gastric cancer, because it may have the effect of irresectable disease becoming resectable.     

Reconstruction of cervical esophageal anastomosis using median sternotomy

We performed cervical oesophageal anastomosis in 153 patients in 10 years. In 11 patients reconstruction or delayed anastomosis was performed through median sternotomy because cervical approach was not suitable. Reoperations were the following: 7 oesophageal stenosis which couldn't be dilated, 2 necrosis of the transplanted organ and 2 because of delayed anastomosis. 8 patients had oesophageal tumors and 3 erosive fluid reflux. During median sternotomy the transplanted organ was injured twice. In 9 patients after reconstruction dysphagia disappeared, in one pharyngo-ileostomy stenosis was noticed and one of the patients died because of ARDS after a leak.     

Sleep disorders and quality of life in renal transplant recipients

Kidney transplantation provides the best outcome for patients with end-stage renal failure both in terms of morbidity and mortality and health-related quality of life (QoL). Health-related QoL has become recognized as an important outcome measure in patients with different chronic medical conditions, including chronic kidney disease (CKD). There are several factors in kidney-transplanted patients which have a negative impact on QoL in these patients. Sleep disorders, such as insomnia, sleep apnea syndrome (SAS), and restless legs syndrome (RLS), are common in kidney-transplanted patients and clearly belong to this group of factors, although there is only limited published data available about the association between sleep problems and QoL in this patient population. The prevalence of both insomnia and RLS is reduced in kidney-transplanted patients compared to dialysis patients, and it is similar to the prevalence observed in the general population. The prevalence of sleep apnea, however, is very high, around 30%. The association between the presence of these sleep disorders and impaired QoL has been relatively well documented in dialysis patients, but there is only scarce published information about this association in the kidney transplant population. In this paper, we will summarize data from the literature describing the impact of sleep problems, which are potentially treatable, on QoL in kidney-transplanted patients. We suggest that the appropriate diagnosis and management of sleep disorders may improve QoL in kidney-transplanted patients.