Development of an Ultrasound Scoring System to Describe Brain Maturation in Preterm Infants.

BACKGROUND AND PURPOSE: Cerebral maturation in preterm infants predominantly occurs postnatally, necessitating the development of objective bedside markers to monitor this process. This study aimed to develop a straightforward objective Ultrasound Score of Brain Development to assess cortical development in preterm infants. MATERIALS AND METHODS: A total of 344 serial ultrasound examinations from 94 preterm infants born at ≤ 32 weeks of gestation were analyzed to identify brain structures suitable for a scoring system. RESULTS: Among 11 candidate structures, 3 cerebral landmarks were selected due to their correlation with gestational age: the interopercular opening (P < .001), the height of the insular cortex (P < .001), and the depth of the cingulate sulcus (P < .001). These structures can be easily visualized in a single midcoronal view in the plane through the third ventricle and the foramina of Monro. A score point from 0 to 2 was assigned to each measurement, culminating in a total score ranging from 0 to 6. The Ultrasound Score of Brain Development correlated significantly with gestational age (P < .001). CONCLUSIONS: The proposed Ultrasound Score of Brain Development has the potential for application as an objective indicator of brain maturation in correlation with gestational age, circumventing the need to rely on individual growth trajectories and percentiles for each specific structure.

Doppler Ultrasound Flow Reversal in the Superior Sagittal Sinus to Detect Cerebral Venous Congestion in Vein of Galen Malformation.

BACKGROUND AND PURPOSE: Vein of Galen malformation is a rare congenital cerebrovascular malformation. In affected patients, increased cerebral venous pressure constitutes an important etiologic factor for the development of brain parenchymal damage. The aim of this study was to investigate the potential of serial cerebral venous Doppler measurements to detect and monitor increased cerebral venous pressure. MATERIALS AND METHODS: This was a retrospective monocentric analysis of ultrasound examinations within the first 9 months of life in patients with vein of Galen malformation admitted at <28 days of life. Categorization of perfusion waveforms in the superficial cerebral sinus and veins into 6 patterns was based on antero- and retrograde flow components. We performed an analysis of flow profiles across time and correlation with disease severity, clinical interventions, and congestion damage on cerebral MR imaging. RESULTS: The study included 44 Doppler ultrasound examinations of the superior sagittal sinus and 36 examinations of the cortical veins from 7 patients. Doppler flow profiles before interventional therapy correlated with disease severity determined by the Bicêtre Neonatal Evaluation Score (Spearman ρ = -0.97, P = < .001). At this time, 4 of 7 patients (57.1%) showed a retrograde flow component in the superior sagittal sinus, whereas after embolization, none of the 6 treated patients presented with a retrograde flow component. Only patients with a high retrograde flow component (equal or more than one-third retrograde flow, n = 2) showed severe venous congestion damage on cerebral MR imaging. CONCLUSIONS: Flow profiles in the superficial cerebral sinus and veins appear to be a useful tool to noninvasively detect and monitor cerebral venous congestion in vein of Galen malformation.

Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, double-blind, placebo-controlled trial

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials. (AU)

[3D-printing in trauma surgery : Planning, printing and processing]. / 3D-Druck in der Unfallchirurgie : Planung, Druck und Aufbereitung.

Possible use of 3D-printing technology in orthopedic surgery ranges from preoperative planning to dedicated counselling with patients by the use of individual 3D models, intraoperative surgery tools or implants and various other applications. This article describes a technique for the creation of intraoperative tools with which the process from computed tomography (CT) images to 3D-printed tools in trauma surgery can safely be administered. For segmentation of CT images a range of different software options is available. The standard triangulation file created in this way (file ending: .stl) must subsequently be post-processed. By the use of the digital casts from bone and fractures in computer-aided design (CAD) programs implants and patient individual tools are created, which can range from ortheses to protheses to intraoperative saw guides.

[Current concepts and new developments of 3D printing in trauma surgery]. / Aktueller Stand und neue Entwicklungen des 3D-Drucks in der Unfallchirurgie.

The use of 3D printing (synonyms "rapid prototyping" and "additive manufacturing") has played an increasing role in the industry for many years and finds more and more interest and application in musculoskeletal surgery, especially orthopedic trauma surgery.In this article the current literature is systematically reviewed, presented and evaluated in a condensed and comprehensive way according to anatomical (upper and lower extremities) and functional aspects. As many of the publications analyzed were feasibility studies, the degree of evidence is low and methodological weaknesses are obvious and numerous; however, this pioneering work is extremely stimulating and important for further development because the technical, medical and economic potential of this technology is huge and interesting for all those involved in the treatment of musculoskeletal problems.

[3D-printed template-assisted reduction of long bone fractures]. / 3D-Druck-Template-gestützte Reposition von Frakturen der langen Röhrenknochen.

INTRODUCTION: In multiply injured patients, the time period between the initial treatment with external fixators (damage control) and the definitive treatment can last from days to weeks. A poor reduction result with the fixator (e.g. malposition in axis, length and rotation) and a long delay from trauma to definitive osteosynthesis are associated with longer operation times, higher intraoperative radiation doses, higher infection rates and an increased likelihood for the necessity to perform an open reduction. MATERIAL AND METHODS: In the described technique computed tomography (CT) is performed after temporary stabilization of the long bone fracture by an external fixator. On the basis of a three-dimensional dataset the fracture can be virtually reduced and a patient-specific reduction fixator can be designed and printed. The 3D printed reduction fixator fits only in the reduced position of the fracture, thus maintaining anatomical bone alignment. The procedure was used for the first time in the Trauma Surgery Clinic of the Medical University Hanover in May 2018 in a polytraumatized female patient with severe brain injury and an open floating knee injury. RESULTS: The procedure could be performed for femoral and tibial shaft fractures. The postoperative CT showed a satisfactory reconstruction of length, torsion and frontal and sagittal plane alignment. Fracture healing was uneventful within 3 months. CONCLUSION: Severely injured patients who initially receive stabilization according to the damage control principle and subsequently remain in the intensive care unit, could particularly benefit from the described postoperative reduction technique. In addition, the reduction fixator can be helpful for the definitive treatment of patients with bilateral fractures of long bones, where a reference to a healthy side is not possible.

[Partial and complete joint transplantation with fresh osteochondral allografts-the FLOCSAT concept]. / Partielle und komplette Gelenktransplantation mit frischen osteochondralen Allografts ­ das FLOCSAT-Konzept.

Cartilage defects in adult patients do not heal well. Fresh osteochondral allograft (OCA) transplantation is based on mature, living, mechanically sound hyaline cartilage attached to a bone interface, which is brought into an osteochondral defect, where it becomes osseointegrated. According to current knowledge, intact hyaline cartilage tissue is immune privileged and does not, in contrast to bone, meniscus or ligaments, cause an immune reaction. The technique has the unique advantage of transplanting viable, mature and mechanically stable hyaline cartilage into the affected area. An OCA is the only biological surgical technique for chondral and osteochondral lesions after failed cell-based techniques or autologous osteochondral transplantation.Fresh osteochondral allografts with mainly small cylindrical transplants show survival of 20 years and more. Based on this experience the FLOCSAT (fresh large [> 10 cm2] osteochondral shell allograft transplantation) concept with the thinnest possible (< 6-8 mm) bone thickness has been developed. Cells survive in special media at 4 °C for 4 weeks or more and are transplanted with a minimum of 70% living cells in a live/dead assay and cell density > 200 cells/mm2.FLOCSATs can replace parts or entire joints as uniplanar or multiplanar(n-planar)-FLOCSAT, as unipolar, bipolar or tripolar(n-polar)-FLOCSAT, and in combination with meniscus and/or ligaments (nMnL)-FLOCSAT (n number of structures).The FLOCSAT concept was applied successfully to knee, ankle and elbow joints. All transplants showed sound osseointegration. Cartilage failure was the reason for unsuccessful outcome. Challenges remain regarding graft availability, precise size matching, complex logistics, demanding surgical technique in complex geometries, and open questions in immunology and chimerism.

Electrocortical Activity at 7 Days of Life is Affected in Extremely Premature Infants with Patent Ductus Arteriosus.

BACKGROUND: The aim of this study was to determine whether the aEEG at 7 days of life is influenced by the presence of a PDA in non-sedated extremely low gestational age preterm infants. PATIENTS: We prospectively recruited infants born at less than 28 weeks of gestation between 11/2007 and 12/2009. METHOD: aEEGs were recorded at seven days of life and assessed by using the Burdjalov score and the electronically assessed lower border (eLBA). Kruskal-Wallis-Test and linear regression analysis were performed to determine how GA and a PDA affect the aEEG score and the eLBA. Using linear regression analysis we tested which components of the score are affected by a PDA. RESULTS: We recruited 44 infants with a GA of 26.5/7 (23.4/7-27.6/7) weeks and a birth weight of 837 (461-1230) g. The total sum of score points increased from 4 (1-6) to 8 (5-9) points in infants born at 23/24 weeks and 27 weeks of gestation, respectively. In infants with relevant PDA the aEEG scored lower with 8 (3-10) points compared to those with PDA: 5 (1-8) points. Linear regression analysis showed a positive influence of GA and a negative influence of a PDA on the total score. GA had a positive influence on SWC and the visually assessed LBA. A PDA had a negative influence on continuity. The eLBA increased from 4.61 (3.18-5.53) µV to 5.27 (3.38-6.51) µV in infants of 23/24 vs. 27 gestational weeks, but was not significantly influenced by a PDA. CONCLUSION: A PDA has a negative influence on the total Burdjalov score and continuity at 7 days of age in infants born at less than 28 weeks of gestation. The electrocortical disturbances may be the consequence of a diminished cerebral perfusion in the presence of a PDA.

Comparison of lipidocolloid and chlorhexidine-impregnated tulle gras dressings following microscopically controlled surgery.

OBJECTIVE: Modified microscopically controlled surgery (MCS) is a staged and margin-controlled excision; after MCS, the selection of an appropriate initial wound dressing plays an important role in wound healing. A wide range of dressings is available for temporary wound coverage; however, data comparing different types of wound dressings after MCS are lacking. The aim of this study was to compare two commonly used and commercially available types of wound dressings. METHOD: We assessed pain levels, wound adherence, bleeding upon dressing removal and signs of infection, with chlorhexidine-impregnated tulle gras and a lipidocolloid dressing used for primary wound dressing following MCS. RESULTS: A total of 42 patients were included. Adherence of the dressing to the wound (p<0.001) and bleeding after removal (p=0.001) were significantly higher in the chlorhexidine-impregnated tulle gras dressing group. Pain during removal of wound dressing had a higher visual analogue scale score (1.9 ± 2.2) in the chlorhexidine-impregnated tulle gras dressing group compared to 0.7 ± 1.0 in the lipidocolloid dressing group (p=0.022). CONCLUSION: The results indicate that the lipidocolloid dressing, when compared with the chlorhexidine-impregnated tulle gras dressing, offers a significant benefit during removal in terms of less pain, less wound adherence and less wound bleeding. DECLARATION OF INTEREST: The authors have no conflict of interest to declare.

Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer.

Trastuzumab (Herceptin) is a humanised monoclonal antibody that specifically targets HER2-positive breast cancer cells. Safety data collected from pivotal trials with trastuzumab indicate that this therapy is generally well tolerated. However trials of the combination of trastuzumab plus chemotherapy, and in particular chemotherapy with anthracyclines, have revealed an elevated incidence of cardiotoxicity in some patients, which was not apparent in preclinical or early clinical studies. Analyses of the available data suggest that in most cases the cardiotoxicity observed may reflect an exacerbation of anthracycline-induced cardiotoxicity. The biological mechanism of the cardiotoxicity has been investigated in several studies, and current data indicate that the heregulin/HER2-signalling pathway may have an important role. It is of note that the cardiotoxicity is generally reversible and can usually be managed with standard medical treatment. Improvement in cardiac function is seen both in patients who continue trastuzumab and in those in whom further therapy is withdrawn, indicating that with careful management anticancer therapy can be continued.

Retrospective analysis of the safety of Herceptin immunotherapy in metastatic breast cancer.

Approximately 25,000 patients have been treated to date with the humanized anti-HER2 monoclonal antibody, Herceptin. This therapy has proved effective and well tolerated in patients with HER2-positive metastatic breast cancer; adverse events were generally infusion-related fever and chills of mild-to-moderate severity. Cardiotoxicity and infusion-related reactions emerged as the two main safety concerns with the use of Herceptin. Retrospective analysis revealed a higher incidence of heart failure when Herceptin was combined with anthracyclines than that expected with anthracyclines alone. Age, anthracycline exposure and cardiac risk factors were found to be predictors of cardiac adverse events. Patients experiencing cardiac dysfunction responded well to standard cardiac medication and the majority improved. Cardiac function should be monitored regularly and Herceptin should be discontinued if significant heart failure develops unless the benefits for an individual patient outweigh the risks. Of 25,000 patients, 74 (0.3%) were reported to have experienced a serious infusion-related reaction. The majority occurred during or shortly after the first infusion and were characterized by respiratory symptoms. Most patients were successfully treated; a total of 33 patients continued Herceptin therapy with no recurrence of infusion reactions. Although the benefit to risk ratio of Herceptin remains favorable, physicians must be vigilant and aggressive in managing cardiotoxicity and infusion-related reactions.

Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial.

OBJECTIVE: To determine whether treatment with creatine can improve exercise intolerance in myophosphorylase deficiency (McArdle disease). DESIGN: Double-blind, placebo-controlled crossover study with oral creatine monohydrate supplementation. PATIENTS: Nine patients with biochemically and genetically proven McArdle disease were treated. INTERVENTION: Five days of daily high-dose creatine intake (150 mg/kg body weight) were followed by daily low-dose creatine intake (60 mg/kg). Each treatment phase with creatine or placebo lasted 5 weeks. MAIN OUTCOME MEASURES: The effect of treatment was estimated at the end of each treatment phase by recording clinical scores, ergometer exercise test results, phosphorus 31 nuclear magnetic resonance spectroscopy, and surface electromyography. RESULTS: Of 9 patients, 5 reported improvement of muscle complaints with creatine. Force-time integrals (P =.03) and depletion of phosphocreatine (P =.04) increased significantly during ischemic exercise with creatine. Phosphocreatine depletion also increased significantly during aerobic exercise (P =.006). The decrease of median frequency in surface electromyograms during contraction was significantly larger (P =.03) with creatine. CONCLUSION: This is the first controlled study indicating that creatine supplementation improves skeletal muscle function in McArdle disease.

[Severe mechanical hemolysis after incomplete ductus arteriosus closure: implantation of a second Rashkind occluder]. / Schwere mechanische Hämolyse nach inkomplettem Duktusverschluss: Implantation eines zweiten Rashkind-Okkluders.

A 72 year-old female patient with a persistent ductus arteriosus suffered from a severe mechanical hemolysis after incomplete PDA closure with a Rashkind occluder. The residual shunt was closed with a second occluder 2 days later. Hemolysis was stopped immediately; complete closure of the duct was confirmed by color Doppler 6 weeks and 6 months later.

Morphologic alterations in small intestinal epithelium of lambs fed vitamin A-depleted diet.

Ten crossbred wether lambs were fed once daily an oat diet that contained 3102 micrograms of retinyl palmitate (control) and were supplemented with 55,000 micrograms of retinyl palmitate orally once every two weeks. Twenty lambs were fed the same oat diet without retinyl palmitate supplements (A-depleted). After being fed the A-depleted diet for 28 weeks, 10 A-depleted lambs were repleted by feeding the control diet and oral supplementation of retinyl palmitate for eight weeks. The A-depleted lambs had serum vitamin A concentrations indicative of vitamin A deficiency, which was supported by very low liver vitamin A concentrations. Light microscopic and ultrastructural examinations revealed that alterations occurred at 50% and 75% of the small intestine length in A-depleted lambs only. Sawtooth configuration of the intestinal epithelium was a distinctive histologic feature. Consistent ultrastructural alterations were vesicular microvillar degeneration and disruption of the capillary endothelium. These results suggests that A-depleted diets have a detrimental effect on the small intestinal epithelium of lambs. Vitamin A repletion appears to minimize the detrimental effects.

Vitamin A deficiency: serum cortisol and humoral immunity in lambs.

Serum cortisol and antigen-specific and polyclonal immunoglobulin G (IgG) concentrations were measured to investigate the relationship between vitamin A status and immune function in lambs. Twenty-four 3-mo-old crossbred ewe lambs weighing approximately 10 kg were each fed 900 g/d of a carotene-deficient diet. The 12 control lambs also received a 100,000 IU oral dose of vitamin A palmitate every 2 wk. All lambs were given primary and secondary antigenic challenges. Lambs were slaughtered at the end of the secondary challenge period. Liver vitamin A concentrations were greater (P less than .001) in the control animals (69.5 vs 1.3 micrograms/g wet tissue). Both groups of lambs exhibited a similar growth response until d 105, after which daily gain of the control lambs exceeded (P less than .03) that of the A-deficient lambs. Polyclonal serum IgG concentrations were greater (P less than .05) in the A-deficient lambs on d 49 to 124 and on d 151 (P less than .10). Ovalbumin-specific serum IgG concentrations tended to be greater in the control lambs throughout the primary and secondary challenge periods. Control lambs had greater titers on d 164 (P less than .07) and d 190 (P less than .03). Vitamin A status appeared to have no consistent effects on serum cortisol concentrations. Spleen weights were greater (P less than .002) in the A-deficient lambs. Lungs from 11 of 12 A-deficient lambs contained abscesses, as opposed to 1 of 12 for the control lambs. Both polyclonal and antigen-specific IgG concentrations were affected by vitamin A status. Serum cortisol concentrations did not appear to mediate this effect.