Femoral nerve block- or intravenous- guided patient control analgesiafor early physical rehabilitation after anterior cruciate ligament reconstruction in "fast-track" orthopedics: what is optimal?

Background and purpose: "Fast-track" orthopaedics characterizes early start of physical rehabilitation (PHR). Quality of mobilization depends on pain therapy success and preservation of motor function and muscle strength. Patient-control-analgesia (PCA), as an upgrade of continuous intravenous (IV) or regional analgesia (FB) makes the modern base in treatment of acute pain. The aim of the study was to determine more effective post-operative PCA-analgesia (IV-PCA vs. FB-PCA) for early PHR in "fast-track" orthopaedics. Materials and Methods: Prospective, observer-blinded study included 40 adults (bought gender, ASA I/II) scheduled for anterior cruciate ligament reconstruction (RACL). Spinal anaesthesia (12.5 mg, 0.5% levobupivacaine; G27-Pencil-Point) was performed in all patients. Patients were divided in two equal groups. In Group IV-PCA intravenous (fentanyl 0.5-1μg kg–1h–1), and in Group FB-PCA regional (femoral block: 0.125% levobupivacaine, 8 ml h–1) PCA-analgesia (Group IV-PCA: fentanil 10μg/8min/x6max; Group FB-PCA: 0.125% levobupivacaine, 8ml/30min/x3max) was established after surgery. Pain score (VAS) was assessed during 24-hours and accepted as satisfactory by 3. Diclofenac 75 i.v. was given in two doses, immediatelly and 12 hours after surgery. Paracetamol 1g was added intravenously if VAS was ³ 4. Start of early PHR was planned six hours after surgery. Result: FB- and IV-PCA provided equally effective analgesia during first 24-hours after RACL (VAS3). Early PHR was possible 6-hours after surgery in 85% of Group FB-PCA (Group IV-PCA=20%) (P=0,0001) due to significantly lower VAS 0,7+/–0,2 (Group IV-PCA=3,0+/–0,2)(P<0,0001). Residual motor block, presented in three patient (15%) with FB-PCA, disabled the onset of PHR.Additional analgesic dose wasmore need inGroup IV-PCA(40%) (Group FB-PCA=10%) (P<0,0001). Conclusion: FB-PCA allows more successful pain-free early PHR for orthopaedics "fast-track" ACL reconstruction compare to IV-PCA, excluding 15% of the FB-PCA patients in whom residual muscle weakness was present

Osteogenesis imperfecta – molekularna osnova i lijekovi budućnosti

Osteogenesis imperfecta (OI) or brittle bone disease is a metabolic bone disease characterized by bone fragility, low bone mass, and increased rate of bone fractures and deformities. Clinical presentation in OI patients shows wide variability ranging from mild to severe and lethal OI types. Advances in molecular biology and studies on animal OI models found at least 16 new genes involved in OI pathogenesis. The majority of mutations are autosomal dominant aff ecting COL1A1 and COL1A2 genes responsible for collagen synthesis. The remaining 10%-15% of mutations in OI are autosomal recessive and aff ect genes involved in various metabolic bone processes. Progress in understanding bone metabolism and genetic engineering off ers new potential therapeutic opportunities that are under diff erent stages of investigation.Osteogenesis imperfecta (OI) ili bolest krhkih kostiju je metabolička bolest kostiju obilježena krhkim kostima, niskom koštanom masom i povišenom stopom lomova i deformiteta kostiju. Klinička prezentacija bolesnika s OI veoma je raznolika, od blagog do teškog i smrtonosnog tipa OI. Napretkom molekularne biologije i istraživanjima na životinjskim modelima OI nađeno je najmanje 16 novih gena uključenih u patogenezu OI. Većina mutacija su autosomno dominantne i zahvaćaju gene COL1A1 i COL1A2 koji su odgovorni za sintezu kolagena. Preostalih 10%-15% mutacija u OI su autosomno recesivne i zahvaćaju gene uključene u razne metaboličke procese u kostima. Sve bolje razumijevanje metabolizma kostiju i genetski inženjering nude nove potencijalne terapijske mogućnosti koje su u različitim fazama ispitivanja

Anterior cruciate ligament reconstruction with anterolateral stabilization by a modified Lemaire technique in adolescent professional football player: a case report

Background: Anterior cruciate ligament (ACL) tear is one of the most common injuries in professional athletes. Additional procedures, such as anterolateral ligament reconstruction and lateral extra-articular tenodesis attempt to reduce rotational instability, the most common cause of re-injury in patients with a nonisolated ACL tear. Case study: A 17-year-old professional football player suffered a right knee injury in a direct hit to the lateral side of the knee. Magnetic resonance imaging showed anterior cruciate ligament tear and lateral knee structures soft tissue contusion. Due to the injury of the lateral structures and the increased risk of ACL rerupture, it was decided to perform ACL reconstruction with additional anterolateral stabilization by a modified Lemaire technique without additional screw fixation in the area of the lateral femoral epicondyle, which could damage the epiphyseal plate and, concurrently, impair bone growth. Conclusion: The addition of lateral extra-articular tenodesis by a modified Lemaire technique prevents rotational instability in a patient with expressed pivotshift before the surgery, without overconstraint of the knee and additional damage to the epiphyseal plate

Identification of human remains from the Second World War mass graves uncovered in Bosnia and Herzegovina

Aim To present the results obtained in the identification of human remains from World War II found in two mass graves in Ljubuški, Bosnia and Herzegovina. Methods Samples from 10 skeletal remains were collected. Teeth and femoral fragments were collected from 9 skeletons and only a femoral fragment from 1 skeleton. DNA was isolated from bone and teeth samples using an optimized phenol/chloroform DNA extraction procedure. All samples required a pre-extraction decalcification with EDTA and additional post-extraction DNA purification using filter columns. Additionally, DNA from 12 reference samples (buccal swabs from potential living relatives) was extracted using the Qiagen DNA extraction method. QuantifilerTM Human DNA Quantification Kit was used for DNA quantification. PowerPlex ESI kit was used to simultaneously amplify 15 autosomal short tandem repeat (STR) loci, and PowerPlex Y23 was used to amplify 23 Y chromosomal STR loci. Matching probabilities were estimated using a standard statistical approach. Results A total of 10 samples were processed, 9 teeth and 1 femoral fragment. Nine of 10 samples were profiled using autosomal STR loci, which resulted in useful DNA profiles for 9 skeletal remains. A comparison of established victims’ profiles against a reference sample database yielded 6 positive identifications. Conclusion DNA analysis may efficiently contribute to the identification of remains even seven decades after the end of the World War II. The significant percentage of positively identified remains (60%), even when the number of the examined possible living relatives was relatively small (only 12), proved the importance of cooperation with the members of the local community, who helped to identify the closest missing persons’ relatives and collect referent samples from them

Early results of intra-articular micro-fragmented lipoaspirate treatment in patients with late stages knee osteoarthritis: a prospective study

Aim To analyze clinical and functional effects of intra-articular injection of autologous micro-fragmented lipoaspirate (MLA) in patients with late stage knee osteoarthritis (KOA). Secondary aims included classifying cell types contributing to the treatment effect, performing detailed MRIbased classification of KOA, and elucidating the predictors for functional outcomes. Methods This prospective, non-randomized study was conducted from June 2016 to February 2018 and enrolled 20 patients with late stage symptomatic KOA (Kellgren Lawrence grade III, n = 4; and IV, n = 16) who received an intra-articular injection of autologous MLA in the index knee joint. At baseline radiological KOA grade and MRI were assessed in order to classify the morphology of KOA changes. Stromal vascular fraction cells obtained from MLA samples were stained with antibodies specific for cell surface markers. Patients were evaluated at baseline and 12-months after treatment with visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS).Results Three patients (15%) received a total knee replacement and were not followed up completely. Seventeen patients (85%) showed a substantial pattern of KOOS and WOMAC improvement, significant in all accounts. KOOS score improved from 46 to 176% when compared with baseline, WOMAC decreased from 40 to 45%, while VAS rating decreased from 54% to 82% (all P values were <0.001). MLA contained endothelial progenitor cells, pericytes, and supra-adventitial adipose stromal cells as most abundant cell phenotypes. Conclusion This study is among the first to show a positive effect of MLA on patients with late stages KOA

Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart

Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45- fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34-CD73±CD90±CD105-CD146± mature endothelial cells, CD31-CD34-CD73±CD90+CD105-CD146+ pericytes, CD31-CD34+CD73±CD90+CD105-CD146+ transitional pericytes, and CD31-CD34+CD73highCD90+CD105-CD146- supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated

GATA transcription factors in testicular adrenal rest tumours

Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation

Genetic variability of the grey wolf Canis lupus in the Caucasus in comparison with Europe and the Middle East: distinct or intermediary population?

Despite continuous historical distribution of the grey wolf (Canis lupus) throughout Eurasia, the species displays considerable morphological differentiation that resulted in delimitation of a number of subspecies. However, these morphological discontinuities are not always consistent with patterns of genetic differentiation. Here we assess genetic distinctiveness of grey wolves from the Caucasus (a region at the border between Europe and West Asia) that have been classified as a distinct subspecies C. l. cubanensis. We analysed their genetic variability based on mtDNA control region, microsatellite loci and genome-wide SNP genotypes (obtained for a subset of the samples), and found similar or higher levels of genetic diversity at all these types of loci as compared with other Eurasian populations. Although we found no evidence for a recent genetic bottleneck, genome-wide linkage disequilibrium patterns suggest a long-term demographic decline in the Caucasian population – a trend consistent with other Eurasian populations. Caucasian wolves share mtDNA haplotypes with both Eastern European and West Asian wolves, suggesting past or ongoing gene flow. Microsatellite data also suggest gene flow between the Caucasus and Eastern Europe. We found evidence for moderate admixture between the Caucasian wolves and domestic dogs, at a level comparable with other Eurasian populations. Taken together, our results show that Caucasian wolves are not genetically isolated from other Eurasian populations, share with them the same demographic trends, and are affected by similar conservation problems

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe