Intranasal human-recombinant nerve growth factor administration improves cognitive functions in a child with severe traumatic brain injury.

BACKGROUND: Behavioral and neuropsychological functions are frequent long-term sequelae of severe traumatic brain injury (TBI). Neuropeptides, such as nerve growth factor (NGF), can enhance neurogenesis and improve cognitive functions after TBI, playing a pivotal role in neuroplasticity. A limited number of studies documented the safety and efficacy of intranasal NGF administration in children with severe TBI. CASE REPORT: A fourteen-year-old boy with a diffuse axonal injury secondary to severe TBI was treated with human-recombinant NGF administration. This patient underwent treatment with intranasal hr-NGF administration at a total dose of 50 gamma/kg, three times a day for seven consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. NGF administration improved radiologic functional assessment evaluated with positron emission tomography scan (PET) and single photon emission computed tomography (SPECT), with an important improvement in clinical conditions. Significant improvements were also observed, mainly in cognitive processes, memory, the planning of a communication strategy, execution skills, attention, and verbal expression. No side effects were reported. CONCLUSIONS: Additional studies are required to gain a deeper insight into this neurotrophin's neuroprotective function, but our findings reveal a potential efficacy of intranasal hr-NGF administration in enhancing cognitive and clinical outcomes among children with diffuse axonal injury after severe TBI.

Automated detection and classification of tumor histotypes on dynamic PET imaging data through machine-learning driven voxel classification.

2-deoxy-2-fluorine-(18F)fluoro-d-glucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) is widely used in oncology mainly for diagnosis and staging of various cancer types, including lung cancer, which is the most common cancer worldwide. Since histopathologic subtypes of lung cancer show different degree of 18F-FDG uptake, to date there are some diagnostic limits and uncertainties, hindering an 18F-FDG-PET-driven classification of histologic subtypes of lung cancers. On the other hand, since activated macrophages, neutrophils, fibroblasts and granulation tissues also show an increased 18F-FDG activity, infectious and/or inflammatory processes and post-surgical and post-radiation changes may cause false-positive results, especially for lymph-nodes assessment. Here we propose a model-free, machine-learning based algorithm for the automated classification of adenocarcinoma, the most common type of lung cancer, and other types of tumors. Input for the algorithm are dynamic acquisitions of PET data (dPET), providing for a spatially and temporally resolved characterization of the uptake kinetic. The algorithm consists in a trained Random Forest classifier which, relying contextually on several spatial and temporal features of 18F-FDG uptake, generates as an outcome probability maps allowing to distinguish adenocarcinoma from other lung histotype and to identify metastatic lymph-nodes, ultimately increasing the specificity of the technique. Its performance, evaluated on a dPET dataset of 19 patients affected by primary lung cancer, provides a probability 0.943 ± 0.090 for the detection of adenocarcinoma. The use of this algorithm will guarantee an automatic and more accurate localization and discrimination of tumors, also providing a powerful tool for detecting at which extent tumor has spread beyond a primary tumor into lymphatic system.

Long-term results after semiconstrained distal radioulnar joint arthroplasty: A focus on complications.

Arthroplasty of the distal radioulnar joint (DRUJ) using a semiconstrained DRUJ implant yields good outcomes according to the literature. The aim of this study was to investigate the subjective, clinical and radiographic outcomes with a special focus on complications in nine patients with a mean follow-up of 6years and to compare them with our previously published 3-year follow-up results. No subjective or objective changes were seen between the 3-year and the 6-year follow-up. In the previous study, one implant loosening and two irritations of the superficial branch of the radial nerve occurred. We saw three complications that needed surgery in addition to the three complications already found 3years after surgery. One patient with a large ulna had loosening of the cemented ulnar stem and therefore the prosthesis was explanted. One patient had an allergic reaction to the metal alloy of the prosthesis, which also led to removal. One patient had an ulnar impaction syndrome caused by too-distal placement of the implant that needed revision. Prior studies reported low complication rates. In our study, six complications occurred in four out of nine patients, requiring reoperation including two revisions and two implant removals. A precise surgical technique is mandatory to avoid the otherwise frequent complications and potential implant failures. LEVEL OF EVIDENCE: IV.

Correction to: Comparison of three-parameter kinetic model analysis to standard Patlak's analysis in 18F-FDG PET imaging of lung cancer patients.

Following publication of the original article [1], the authors flagged that the author affiliations detailed in the article are incorrect for the authors M. L. Calcagni and A. Giordano.

Comparison of three-parameter kinetic model analysis to standard Patlak's analysis in 18F-FDG PET imaging of lung cancer patients.

BACKGROUND: Patlak's graphical analysis can provide tracer net influx constant (Ki) with limitation of assuming irreversible tracer trapping, that is, release rate constant (kb) set to zero. We compared linear Patlak's analysis to non-linear three-compartment three-parameter kinetic model analysis (3P-KMA) providing Ki, kb, and fraction of free 18F-FDG in blood and interstitial volume (Vb). METHODS: Dynamic PET data of 21 lung cancer patients were retrospectively analyzed, yielding for each patient an 18F-FDG input function (IF) and a tissue time-activity curve. The former was fitted with a three-exponentially decreasing function, and the latter was fitted with an analytical formula involving the fitted IF data (11 data points, ranging 7.5-57.5 min post-injection). Bland-Altman analysis was used for Ki comparison between Patlak's analysis and 3P-KMA. Additionally, a three-compartment five-parameter KMA (5P-KMA) was implemented for comparison with Patlak's analysis and 3P-KMA. RESULTS: We found that 3P-KMA Ki was significantly greater than Patlak's Ki over the whole patient series, + 6.0% on average, with limits of agreement of ± 17.1% (95% confidence). Excluding 8 out of 21 patients with kb > 0 deleted this difference. A strong correlation was found between Ki ratio (=3P-KMA/Patlak) and kb (R = 0.801; P < 0.001). No significant difference in Ki was found between 3P-KMA versus 5P-KMA, and between 5P-KMA versus Patlak's analysis, with limits of agreement of ± 23.0 and ± 31.7% (95% confidence), respectively. CONCLUSIONS: Comparison between 3P-KMA and Patlak's analysis significantly showed that the latter underestimates Ki because it arbitrarily set kb to zero: the greater the kb value, the greater the Ki underestimation. This underestimation was not revealed when comparing 5P-KMA and Patlak's analysis. We suggest that further studies are warranted to investigate the 3P-KMA efficiency in various tissues showing greater 18F-FDG trapping reversibility than lung cancer lesions.

Retrograde fixation of metacarpal fractures with intramedullary cannulated headless compression screws.

We analyzed the results of 20 unstable metacarpal fractures in 15 patients treated with a cannulated compression screw and no immobilization. All fractures healed within 6 weeks. One patient with multiple fractures and a flexion deficit required arthrolysis of two metacarpophalangeal joints. Another patient had an extension lag. There were no other complications. This fast and easy technique results in good outcomes for unstable metacarpal fractures. The advantages are early active motion without immobilization and stable fixation. Surgical removal of the screw is rarely needed. LEVEL OF EVIDENCE: IV (therapeutic).

Postoperative imaging of orthopaedic hardware in the hand and wrist: is there an added value for tomosynthesis?

AIM: To prospectively investigate digital tomosynthesis (DTS) as an alternative to digital radiography (DR) for postoperative imaging of orthopaedic hardware after trauma or arthrodesis in the hand and wrist. MATERIALS AND METHODS: Thirty-six consecutive patients (12 female, median age 36 years, range 19-86 years) were included in this institutional review board approved clinical trial. Imaging was performed with DTS in dorso-palmar projection and DR was performed in dorso-palmar, lateral, and oblique views. Images were evaluated by two independent radiologists for qualitative and diagnosis-related imaging parameters using a four-point Likert scale (1=excellent, 4not diagnostic) and nominal scale. Interobserver agreement between the two readers was assessed with Cohen's kappa (k). Differences between DTS and CR were tested with Wilcoxon's signed-rank test. A p-value <0.05 was considered statistically significant. RESULTS: Regarding image quality, interobserver agreement was higher for DTS compared to DR, especially for fracture-related parameters (delineation osteosynthesis material [OSM]: KDTS0.96 versus KDR0.45; delineation fracture margins: KDTS0.78 versus KDR0.35). Delineation of fracture margins and delineation of adjacent joint spaces scored significant better for DTS compared to DR (delineation fracture margins: DTS1.54, DR2.28, p0.001; delineation adjacent joint spaces: DTS1.31, DR2.24, p0.001). Regarding diagnosis-related findings, interobserver agreement was almost equal. DTS showed a significant higher sharpness of fracture margins (DTS1.94, DR2.33, p0.04). Mean dose area product (DAP) for DTS was significant higher compared to DR (mean DR0.219 Gy·cm2, mean DTS0.903 Gy·cm2, p0.001). CONCLUSION: Fracture healing is more visible and interobserver agreement is higher for DTS compared to DR in the postoperative assessment of orthopaedic hardware in the hand and wrist.

The influence of Generalized Anxiety Disorder on Executive Functions in children with ADHD.

The present study was aimed at verifying whether the presence of generalized anxiety disorder (GAD) affects executive functions in children with attention-deficit hyperactivity disorder (ADHD). Two groups of children with ADHD were selected for the study according to the presence or absence of GAD. The first group of 28 children with ADHD with GAD (mean age: 9 ± 1.2; males/females: 24/4) was matched for gender, age, IQ, psychiatric comorbidity with a second group of 29 children with ADHD without GAD (mean age: 8.8 ± 0.7; males/females: 26/3). The two groups with ADHD were compared to 28 typically developing children (mean age: 8.3 ± 1.3; males/females: 23/5) on different measures involving processes especially important in inhibitory control such as rule maintenance, stimulus detection, action selection and action execution. Our results indicated that, differently from children with ADHD with GAD, only the group with ADHD without GAD showed a deficit in inhibitory control. Comorbid subgroups should be differentiated, especially, to develop specific and efficient therapeutic interventions in ADHD.

Gene expression in human adipose-derived stem cells: comparison of 2D films, 3D electrospun meshes or co-cultured scaffolds with two-way paracrine effects.

Finding the appropriate cues to trigger the desired differentiation is a challenge in tissue engineering when stem cells are involved. In this regard, three-dimensional environments are often compared to cells' two-dimensional culture behaviour (plastic culture dish). Here, we compared the gene expression pattern of human adipose-derived stem cells (ASC) seeded in a three-dimensional (3D) electrospun mesh and on a two-dimensional (2D) film - both of exactly the same material. Additionally, we conducted experiments with a scaffold floating above a film to investigate two-way paracrine effects (co-system). Electrospun meshes (3D scaffolds) and films (2D), consisting either of pristine poly-lactic-co-glycolic acid (PLGA) or of PLGA-containing dispersed amorphous calcium phosphate nanoparticles (PLGA/aCaP), were seeded with ASCs and cultured either in Dulbecco Minimum Essential Medium (DMEM) or in osteogenic medium. After two weeks, minimum stem cell criteria markers as well as typical markers for osteogenesis, endothelial cell differentiation, adipogenesis and chondrogenesis were analysed by quantitative real-time PCR. Interestingly, mostly osteogenic genes of cells seeded on 3D meshes were upregulated compared to those on 2D films, while stem cell markers seemed to be only slightly affected. Runx2 and osteocalcin showed an especially strong upregulation under all conditions, while most other factors analysed for 2D/3D changes were highly dependent on the material composition, the culture medium and on paracrine signalling effects. The beneficial 3D environment for stem cells found in many studies has therefore not to be attributed to the third dimension alone and should carefully be compared to 2D films fabricated of the same material. Furthermore, paracrine interactions triggering differentiation are not negligible.

Complications after treating Dupuytren's disease. A systematic literature review.

The objective of this study was to review the incidence of complications associated with different treatment options for patients with Dupuytren's disease. In a systematic literature review, the PubMed, EMBASE, Cochrane and Scopus databases were searched for clinical studies reporting complications after collagenase treatment, percutaneous needle fasciotomy (PNF), fasciectomy and dermofasciectomy. The incidence of complications was extracted from each study and stratified by procedure. From a total of 2251 references, 113 studies were analyzed and included with complication incidences varying from 0% to 100%. The highest number of nerve and vessel lesions were reported after fasciectomy, whereas the highest rate of edema was after collagenase injection. Accidental skin tears were mostly associated with collagenase and PNF treatment. Pooled complication incidences were 17.4% (95% CI: 11.7-23.1) for fasciectomy, 78.0% (95% CI: 59.6-96.4) for collagenase treatment, 18.9% (95% CI: -5.5-43.3) for PNF and 11.6% (95% CI: 0.0-23.2) for dermofasciectomy. Due to inconsistencies in reporting complications as well as the lack of a standardized definition, the literature does not provide evidence in favor of a specific procedure for Dupuytren's disease. A standardized definition of complications is required to improve the comparability of published results.

IFSSH scientific committee on skin coverage: 2015 report.

Skin coverage in hand reconstruction is a challenging and vast chapter in hand surgery; covering every aspect of it in a report is simply not feasible. Therefore, this report focuses on a few specific topics. The coverage of anatomical regions like the fingertips is common ground for hand surgeons worldwide, but in the last 10 years, various refinements have been published in order to optimize the reconstruction of this organ. Nevertheless, in many emergency departments, the amputation of badly injured fingertips, including the thumb, remains the preferred treatment. The main focus of this report is to counter this tendency by providing alternatives to surgeons. Large defects in the fingers involving more than one segment, defects in the palm and in the dorsum of the hand are currently debated in international meetings. The use of skin substitutes vs. the use of extremely refined microsurgical procedures vs. classic island flaps has generated animated discussions, which are also influenced by cultural and socioeconomic factors around the world. This report offers the views of six surgeons from four different countries, in the hope of animating discussions and suggesting new approaches.

Modified Suzuki frame for the treatment of difficult Rolando fractures.

Fifteen consecutive patients with severely comminuted Rolando fractures were treated by closed reduction and fixation with a modified Suzuki frame without rubber bands, followed by immediate mobilization. All the fractures healed within 5 weeks. At 3 months, no rotational deformity was observed. The Kapandji score was equal that of the contralateral thumb in eight cases. No residual pain was recorded. Grip strength was 78% and pinch strength was 78% of the contralateral hand. One patient needed the frame tension modified. One patient developed a sensory deficit in the area of the superficial branch of the radial nerve that resolved spontaneously in 3 months. One patient healed with a 2-mm articular step-off, but the clinical outcome was good. Our retrospective study suggests that the small modification we made to the Suzuki frame provides a relatively simple and minimally invasive technique for the treatment of comminuted Rolando fractures.

Midterm Results of Semiconstrained Distal Radioulnar Joint Arthroplasty and Analysis of Complications.

Range of motion and stability are important outcome parameters to assess function of the distal radioulnar joint (DRUJ), in particular pronation, supination, and weight-lifting capacity. The DRUJ semiconstrained implant developed by Scheker et al is intended to reproduce all the functions of the triangular fibrocartilage complex and the DRUJ. The aim of the study was to investigate the subjective, clinical, and radiographic results in 10 patients after primary implantation of the semiconstrained DRUJ arthroplasty following DRUJ derangement and painful instability, with an average follow-up of 3 years with a special focus on the complications. Standardized preoperative and postoperative evaluation included assessment of pain by a visual analog scale, radiographic examination, range of motion measurements, lifting capacity, and grip strength. The patient-perceived function was investigated using clinical score charts. Compared with the preoperative status, range of motion showed little change, while grip strength, lifting capacity, pain score, and patient-perceived functions improved significantly. One patient developed an ulna stem loosening, while two patients had to be reoperated because of an irritation of the extensor tendons and the superficial radial nerve at the first dorsal compartment of the wrist. In this study, arthroplasty of the DRUJ using the semiconstrained DRUJ arthroplasty was found to result in satisfactory outcome. Level of evidence: Level IV.

Intramedullary headless screw fixation for fractures of the proximal and middle phalanges in the digits of the hand: a review of 31 consecutive fractures.

UNLABELLED: We present the results of 26 patients with 31 consecutive displaced or unstable extra-articular fractures of the base and shaft of the proximal and middle phalanges of the digits of the hand, treated over a period of 12 months with an intramedullary headless compression screw and early mobilization with no splinting. All fractures healed with no major complications. Only one patient, who had a pathological fracture through an enchondroma, required a tenolysis to improve the mobility of the finger. This technique seems to be technically simple, effective and with few drawbacks. LEVEL OF EVIDENCE: IV.

Treatment of proximal phalangeal fractures with an antegrade intramedullary screw: a cadaver study.

The aim of this study was to quantify the articular cartilage defect created with two different antegrade techniques of intramedullary osteosynthesis with a headless compression screw inserted through the metacarpophalangeal joint. In 12 out of 24 fingers from six cadaveric hands, a trans-articular technique with cannulated headless compression screws (2.2 and 3.0 mm diameter) was used; whereas in the other 12 fingers, an intra-articular fixation technique was used. The areas of the articular surface and the defects created were measured with a digital image software program. All measurements were made twice by two observers. In the intra-articular technique, the average defect in the base of the articular surface of the proximal phalanx was 4.6% with the 2.2 mm headless compression screw and 8.5% with the 3.0 mm screw. In the trans-articular technique, the defect size was slightly smaller; 4.2% with the 2.2 mm screw and 8% with the 3.0 mm screw, but the differences were not statistically significant. The main advantage of the intra-articular technique was that it avoided damage to the articular surface of the metacarpal head.

Extending the limits of reconstructive microsurgery in elderly patients.

BACKGROUND: Population aging strongly affects the demographic development of industrialized countries. While microsurgical procedures were initially believed to be only feasible in patients of younger age because of the duration of the surgical procedure and the higher risk of vascular insufficiency due to age-related comorbidities, it has become evident that these procedures are beneficial even for patients at an advanced age. METHODS: We retrospectively investigated microsurgical procedures in a patient cohort (n = 25 with 27 free flaps) with a minimum age of 78 years with regard to patients' characteristics, flap survival, and postoperative surgical and medical complications. RESULTS: Median age was 81 years (IQR 6). Most defects were located in the head and neck region. The mean operation time was 384 min (standard deviation (SD) 131). Flap failure was observed in three cases (11%). The median length of hospital stay was 17 days (interquartile range (IQR) 8). The mean ASA score was 2.48. Patients' age and ASA group did not correlate. The mortality rate was 4%. Postoperative surgical complications were observed in 11 cases (41%), while 19 patients (70%) showed one or more medical complications. Higher ASA classes tended to show more postoperative complications. However, neither age nor operating time nor ASA status showed significant influence on the occurrence of postoperative medical or surgical complications. CONCLUSION: There is growing demand for structural and functional restoration using free tissue transfer in an aging population. If there are no alternative treatment options available promising similar structural and functional preservation, free tissue transfer is justifiably in very old patients despite a potentially increased flap failure. As such, free tissue transfer is used as a curative treatment concept aiming at a maximum of patients' independence and early ambulation. Occurrence of complications can be diminished by adequate patient selection and thorough perioperative care.

Long-term clinical outcome after epineural coaptation of digital nerves.

UNLABELLED: This study evaluates the long-term clinical outcome and complication rate after digital nerve repair in adults and aims to identify possible prognostic factors of sensory recovery. End-to-end epineural coaptation was performed under magnification. A total of 93 coapted digital nerves were clinically evaluated with a mean follow-up of 3.5 years (range 1-6 years). The mean two-point discrimination was 10.6 mm (versus 4.4 mm for the contralateral side). Cutaneous pressure threshold tested with Semmes-Weinstein monofilaments showed a mean value of 2.7 (versus 2.2 for the contralateral side). Only 2% of our patients developed painful neuromas. None of our patients recovered normal functional sensibility, however, recovery of protective sensation contributed to a high reported level of satisfaction. No correlation was observed between the sensory outcome and age, smoking, mechanism of injury, lesion to or anastomosis of a digital artery, or time of immobilization. The only identified predictor of the result was the surgeon's level of experience. This highlights the importance of adequate training and practice in the surgical repair of smaller peripheral nerves. LEVEL OF EVIDENCE: IV.