Novosti u artroskopskoj kirurgiji ručnog zgloba: od resekcije do rekonstrukcije

One of the major advances in wrist arthroscopy is the development of various therapeutic procedures since the 90’s. Therapeutic procedures are no longer restricted to resection. More specific repair procedures and functional reconstruction involving replenishment of tissue defect and augmentation of vital structures are seen with proven value. In particular, wrist arthroscopy performed under local anaesthetic setting without tourniquet and sedation markedly reduces the risk and cost. This article highlights the common indications and applications of wrist arthroscopy, with emphasis on the latest and significant innovations in reconstructive arthroscopic surgery in Hong Kong. On the resection aspect, common procedures include joint debridement, synovectomy, ganglionectomy, capsular release and osteotomies. Reparative surgery includes ligament repair, arthroscopic assisted reduction and fixation of fracture dislocation and chondroplasty for small chondral lesions. Reconstructive surgery embraces surgical solutions tackling on osseous, soft tissue and cartilage problems. Scaphoid nonunion can be treated by arthroscopic bone grafting and percutaneous fixation with union rate of over 90 %. Partial wrist fusion can be achieved arthroscopically to maximize motion and to enhance union by preserving soft tissue and vascularity. Arthroscopic assisted reconstruction of the radio-ulnar ligaments with tendon graft can be performed to treat chronic distal radioulnar joint instability through bone tunnels in sigmoid notch and ulnar fovea. In chronic scapholunate (SL) instability, the dorsal and palmar portion of the SL interosseous ligament is reconstituted anatomically through arthroscopically assisted reconstruction with tendon graft in a box-like structure. In cartilage reconstruction, post–traumatic chondral lesion can be treated with arthroscopic osteochondral transplant.Od uvođenja artroskopije ručnog zgloba 90-ih godina prošloga stoljeća počinje razvoj i uvođenje brojnih novih terapijskih postupaka. Zahvati više nisu ograničeni samo na resekcije, već se počinje s razvojem reparacijskih i funkcionalnih rekonstrukcija, kao što su popunjavanje defekata i augmentacija vitalnih struktura. Artroskopija ručnog zgloba izvedena u lokalnoj anesteziji i bez Torniquetove poveske značajno smanjuje i cijenu zahvata. U ovom radu istaknute su najčešće indikacije i primjena artroskopija ručnog zgloba s naglaskom na najnoviji zahvat artroskopske rekonstrukcije ručnog zgloba u Hong Kongu. Glede resekcija, najčešći zahvati uključuju debridman zgloba, sinovijektomiju, ganglionekotimiju, opuštanje zglobne čahure i oteotomiju. Reparativni zahvati uključuju rekonstrukcije ligamenata, artroskopski asistirane repozicije i fiksacije prijeloma i luksacija te hondroplastike. Rekonstruktivni zahvati obuhvaćaju zahvate na kostima, mekim tkivima i hrskavici. Nesraštanje skafoidne kosti može se liječiti artroskopski s koštanim presadcima i perkutanim fiksacijama, a uspješnost cijeljenja je veća od 90 %. Djelomične artrodeze mogu se provesti artroskopski kako bi se očuvala pokretljivost ostalih dijelova i pojačalo cijeljenje očuvanjem mekih tkiva i vaskularizacije. Artroskopski asistirana rekonstrukcija radioularnih ligamenata s tetivnim transplantatima može se izvoditi pri kroničnim nestabilnostima distalnog radioulnarnog zgloba. Pri kroničnoj skafolunatnoj nestabilnosti, dorzalni i palmarni dio SL ligamenta mogu se anatomski rekonstruirati tetivnim presadcima. Posttraumatska hrskavična oštećenja mogu se liječiti artroskopski primjenom koštano-hrskavičnih transplantata

Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients

Exhaled Nitric Oxide is Associated with Allergic Inflammation in Children

Exhaled nitric oxide (eNO) has been proposed as a noninvasive marker of airway inflammation in asthma. In asthmatic patients, exhaled NO levels have been shown to relate with other markers of eosinophilic recruitment, which are detected in blood, sputum, bronchoalveolar lavage fluid and bronchial biopsy samples. The purpose of this study was to assess the possible relationship between eNO and allergic inflammation or sensitization in childhood asthma and allergic rhinitis. Subjects consisted of 118 asthmatic children, 79 patients with allergic rhinitis, and 74 controls. Their age ranged from 6 to 15 yr old. eNO level, peripheral blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE level and specific IgE levels were measured. Methacholine challenge test and allergic skin prick test for common allergens were performed in all subjects. Atopic group (n = 206, 44.48 ± 30.45 ppb) had higher eNO values than non-atopic group (n = 65, 20.54 ± 16.57 ppb, P < 0.001). eNO level was significantly higher in patients with asthma (42.84 ± 31.92 ppb) and in those with allergic rhinitis (43.59 ± 29.84 ppb) than in healthy controls (27.01 ± 21.34 ppb, P < 0.001) but there was no difference between asthma and allergic rhinitis group. eNO also had significant positive correlations with Dermatophagoides pteronyssinus IgE level (r = 0.348, P < 0.001), Dermatophagoides farinae IgE level (r = 0.376, P < 0.001), and the number of positive allergens in skin prick test (r = 0.329, P = 0.001). eNO had significant positive correlations with peripheral blood eosinophil count (r = 0.356, P < 0.001), serum total IgE level (r = 0.221, P < 0.001), and ECP (r = 0.436, P < 0.001). This study reveals that eNO level is associated with allergic inflammation and the degree of allergic sensitization

Old Technique -New Evidence: Topical agents for musculo-skeletal injuries

The popular use of topical agents for the treatment of musculoskeletal injuries has persisted for centuries but not much scientific evaluations have been done. Since medicinal herbs are particularly popular in Asia, we started a systematic exploration on their choices, and their pharmacological activities; whether transcutaneous transport of bioactive components occur and above all, whether quality clinical evidences could be generated. We found that a search on the vast literature pool would reveal the favourable choices of herbal agents. Biological screening of those selected herbs showed that they probably follow three major common pathways to help with healing after injury, viz, anti-inflammation, pro-angiogenesis and cellular proliferation. Using a simple formula of selected herbs with the ideal bioactivities, evidence based clinical trials could be organized to further prove the efficacy. We have created two such formulae to be put on clinical trial. Our early pilot clinical trials on two minor injuries on the foot and one chronic inflammatory condition have yielded positive data on the value of such topical agents on pain and oedema control, as well as functional maintenance. There was also suggestion of more rapid bone healing. Although limitations exist clear with the small number of study subjects, the positive data and safe application support more studies

Dietary compound Isoliquiritigenin prevents mammary carcinogenesis by inhibiting breast cancer stem cells through WIF1 demethylation

Breast cancer stem cells (CSCs) are considered as the root of mammary tumorigenesis. Previous studies have demonstrated that ISL efficiently limited the activities of breast CSCs. However, the cancer prevention activities of ISL and its precise molecular mechanisms remain largely unknown. Here, we report a novel function of ISL as a natural demethylation agent targeting WIF1 to prevent breast cancer. ISL administration suppressed in vivo breast cancer initiation and progression, accompanied by reduced CSC-like populations. A global gene expression profile assay further identified WIF1 as the main response gene of ISL treatment, accompanied by the simultaneous downregulation of β-catenin signaling and G0/G1 phase arrest in breast CSCs. In addition, WIF1 inhibition significantly relieved the CSC-limiting effects of ISL and methylation analysis further revealed that ISL enhanced WIF1 gene expression via promoting the demethylation of its promoter, which was closely correlated with the inhibition of DNMT1 methyltransferase. Molecular docking analysis finally revealed that ISL could stably dock into the catalytic domain of DNMT1. Taken together, our findings not only provide preclinical evidence to demonstrate the use of ISL as a dietary supplement to inhibit mammary carcinogenesis but also shed novel light on WIF1 as an epigenetic target for breast cancer prevention.published_or_final_versio

Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly.

Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1:1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP-STIL interaction constitutes a conserved key step in centriole biogenesis. DOI:http://dx.doi.org/10.7554/eLife.01071.001

DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers

Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours

Novel echocardiographic techniques to assess left atrial size, anatomy and function

Three-dimensional echocardiography (3DE) and speckle tracking echocardiography (STE) have recently applied as imaging techniques to accurately evaluate left atrial (LA) size, anatomy and function. 3DE and off-line quantification softwares, have allowed, in comparison to magnetic resonance imaging, the most time-efficient and accurate method of LA volume quantification. STE provides a non-Doppler, angle-independent and objective quantification of LA myocardial deformation. Data regarding feasibility, accuracy and clinical applications of LA analysis by 3DE and STE are rapidly gathering. This review describes the fundamental concepts of LA 3DE and STE, illustrates how to obtain respective measurements and discuss their recognized and emerging clinical applications