COVID-19: Initial experience of an international group of hand surgeons.

The emergence of the COVID-19 pandemic has severely affected medical treatment protocols throughout the world. While the pandemic does not affect hand surgeons at first glance, they have a role to play. The purpose of this study was to describe the different measures that have been put in place in response to the COVID-19 pandemic by hand surgeons throughout the world. The survey comprised 47 surgeons working in 34 countries who responded to an online questionnaire. We found that the protocols varied in terms of visitors, health professionals in the operating room, patient waiting areas, wards and emergency rooms. Based on these preliminary findings, an international consensus on hand surgery practices for the current viral pandemic, and future ones, needs to be built rapidly.

[Robotic head and neck surgery at the Chinese University of Hong Kong].

Introduction:Robotic surgery in the head and neck region has been used to approach many different areas within the head and neck region. Here we describe our experiences of its application at The Chinese University of Hong Kong.Methods:This is a retrospective review of all cases operated by the two authors since Jan 2015 at the Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong.Results:Twenty-four cases were performed with the da Vinci S or da Vinci Xi systems. Twenty-one cases were performed with the novel flexible robotic da Vinci SP system. There were no serious adverse events requiring a return to the operating room. Early results from the da Vinci SP have been previously published in seven patients that demonstrated the ability to reach the nasopharynx, oropharynx, hypopharynx, larynx and also retropharyngeal lymph nodes. There were no conversions to alternative surgical approaches. There were no serious adverse events or adverse events related to the use of this system.Discussion:In conclusion, through our experiences at The Chinese University of Hong Kong we have found the da Vinci robotic systems to be useful and safe in performing TORS and addressing pathologies in the neck through the retroauricular approach.

A metagenomic study of the preventive effect of Lactobacillus rhamnosus GG on intestinal polyp formation in ApcMin/+ mice.

AIMS: To investigate the in vivo effects of Lactobacillus rhamnosus GG (LGG) on intestinal polyp development and the interaction between this single-organism probiotic and the gut microbiota therein. METHODS AND RESULTS: The ApcMin/+ mouse model was used to study the potential preventive effect of LGG on intestinal polyposis, while shotgun metagenomic sequencing was employed to characterize both taxonomic and functional changes within the gut microbial community. We found that the progression of intestinal polyps in the control group altered the community functional profile remarkably despite small variation in the taxonomic diversity. In comparison, the consumption of LGG helped maintain the overall functional potential and taxonomic profile in the resident microbes, thereby leading to a 25% decrease of total polyp counts. Furthermore, we found that LGG enriched those microbes or microbial activities related to short-chain fatty acid production (e.g. Roseburia and Coprococcus), as well as suppressed the ones that can lead to inflammation (e.g. Bilophila wadsworthia). CONCLUSIONS: Our study using shotgun metagenomics highlights how single probiotic LGG may exert its beneficial effects and decrease polyp formation in mice by maintaining gut microbial functionality. SIGNIFICANCE AND IMPACT OF THE STUDY: This probiotic intervention targeting microbiota may be used in conjugation with other dietary supplements or drugs as part of prevention strategies for early-stage colon cancer, after further clinical validations in human.

Synthesis of platinum(II) and palladium(II) complexes with 9,9-dihexyl-4,5-diazafluorene and their in vivo antitumour activity against Hep3B xenografted mice.

Two complexes dichloro(9,9-dihexyl-4,5-diazafluorene)platinum(II) (Pt-DHF) and dichloro(9,9-dihexyl-4,5-diazafluorene)palladium(II) (Pd-DHF) were synthesized and their in vivo antitumour activity was investigated using an athymic nude mice model xenografted with human Hep3B carcinoma cells. Pt-DHF- and Pd-DHF-treated groups showed significant tumour growth inhibition (with about 9-fold and 3-fold tumour growth retardation) when compared with the vehicle control group. The liver toxicology effects on the animals of the two compounds were investigated. Pt-DHF and Pd-DHF-treated groups had a lower alanine transaminase and aspartate transaminase values than those of the vehicle treated group as the animals from the vehicle control group had very heavy hepatoma burden. We assume that both complexes could be further investigated as effective antitumour agents and it is worthwhile to study their underlying working mechanism.

Antiangiogenic activity of 2-formyl-8-hydroxy-quinolinium chloride.

Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.

Synthesis of hexahydrofuro[3,2-c]quinoline, a martinelline type analogue and investigation of its biological activity.

BACKGROUND: Candida susceptibility commonly occurs in breast cancer patients. Of which, Candida albicans is considered as a common pathogen causing candidiasis. Martinella iquitosensis (Bignoniaceae) is one of the species belonged to Martinella, distributed widely in Amazon basin. Its root extract yielded two complex substituted tetrahydroquinolines, Martinelline and Martinellic acid which were the first natural non-peptide bradykinin receptor antagonists identified. FINDINGS: In this study, a novel martinelline type analogue, named 2,3,3a,4,5,9b-hexahydro-8-phenoxy-4-(pyridin-2-yl)furo[3,2-c]quinoline, was synthesized and its preliminary anticancer activity and antifungal potential were investigated. This compound showed potential anticancer activity against MDAMB-231 breast cancer cells. Meanwhile it could enhance the fungistatic activity of miconazole against Candida albicans. CONCLUSIONS: These findings provide an implication for the continue investigation and development of martinelline type analogues as therapeutic agents in the future.

Thoracoscopic repair of congenital diaphragmatic hernia: two centres' experience with 60 patients.

INTRODUCTION: Congenital diaphragmatic hernia is a potentially life-threatening neonatal condition which required surgical intervention. With the advances in endosurgical instruments and techniques, thoracoscopic approach is gaining popularity as a standard procedure in the treatment of this condition. In this study, we reviewed our two centres' experience with thoracoscopic repair of congenital diaphragmatic hernia in recent years. METHODS: All patients who underwent thoracoscopic repair of congenital diaphragmatic hernia between 2010 and 2013 at the two tertiary referral centres were identified. Medical records were retrospectively reviewed. Data including patients' demographics, peri-operative outcomes, length of hospitalisation and post-operative complications were extracted and analysed. RESULTS: 60 patients were identified over the study period, with 46 males and 14 females. 48 patients received operation within the first 7 days of life. There were seven patients with delayed presentation and were operated after 1 month old. The average body weight was 3.03 kg. Left-sided hernia was more prevalent (n = 50). The mean operative time was 88.5 min (range 31-194 min). No conversion to open thoracotomy or laparotomy was required in any of the patients. All patients except one were intubated and paralysed in neonatal intensive care units for at least 3 days after operation. Average hospital stay was 14.6 days. There was no mortality in this series. There were five recurrences, one being the patient without post-operative paralysis, and the others with deficient posterior muscle rim. No musculoskeletal deformity was noted on follow-up examination. CONCLUSION: Thoracoscopic repair of congenital diaphragmatic hernia can be performed safely in specialised centres. The post-operative recovery and cosmesis are excellent. Diaphragmatic hernia with large defect remains a challenge for surgeons.

Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study.

Haemostatic management of haemophilia B patients undergoing surgery is critical to patient safety. The aim of this ongoing prospective trial was to investigate the haemostatic efficacy and safety of a recombinant factor IX (rFIX) (Bax326) in previously treated subjects (12-65 years, without history of FIX inhibitors) with severe or moderately severe haemophilia B, undergoing surgical, dental or other invasive procedures. Haemostatic efficacy was assessed according to a predefined scale. Blood loss was compared to the average and maximum blood loss predicted preoperatively. Haemostatic FIX levels were achieved peri- and postoperatively in 100% of subjects (n = 14). Haemostasis was 'excellent' intraoperatively in all patients and postoperatively in those without a drain, and 'excellent' or 'good' at the time of drain removal and day of discharge in those with a drain employed. Following the initial dose, the mean FIX activity level rose from 6.55% to 107.58% for major surgeries and from 3.60% to 81.4% for minor surgeries. Actual vs. predicted blood loss matched predicted intraoperative blood loss but was equal to or higher than (but less than 150%) the maximum predicted postoperative blood loss reflecting the severity of procedure and FIX requirements. There were no related adverse events, severe allergic reactions or thrombotic events. There was no evidence that BAX326 increased the risk of inhibitor or binding antibody development to FIX. BAX326 was safe and effective for peri-operative management of 14 subjects with severe and moderately severe haemophilia B.

SURgical interventions with FEIBA (SURF): international registry of surgery in haemophilia patients with inhibitory antibodies.

Factor VIII Inhibitor Bypassing Activity (FEIBA) can effectively achieve haemostasis in haemophilia patients with inhibitors. Further evaluation of FEIBA in surgical settings is of significant interest considering the relatively limited prospective data published to date. The aim of the study is to evaluate the perioperative efficacy and safety of FEIBA in haemophilia patients with inhibitors. Haemophilia patients with inhibitors who underwent surgical procedures and received FEIBA for perioperative haemostatic control were prospectively enrolled in an open-label, noninterventional, postauthorization study [SURgical interventions with FEIBA (SURF)]. Outcome measures included haemostatic efficacy, safety, FEIBA exposure and blood loss associated with the perioperative use of FEIBA. Thirty-five surgical procedures were performed at 19 centres worldwide in patients with congenital haemophilia A, congenital haemophilia B, or acquired haemophilia A. Haemorrhagic risk was severe in 37.1% (13 of 35) of the procedures, moderate in 25.7% (9 of 35) and mild in 37.1% (13 of 35). One moderate risk surgery was excluded from the efficacy analyses because it did not meet all protocol requirements. Haemostasis was judged to be 'good' or 'excellent' in 91.2% (31 of 34) of surgical procedures and 'fair' in 8.8% (3 of 34). Among the 12 adverse events, three were serious adverse events (SAEs), two of which were unrelated to FEIBA therapy; one SAE, a clot in an arteriovenous fistula, was deemed to be possibly related to therapy. This prospective investigation confirms that FEIBA can be safely and effectively used when performing surgical procedures in haemophilia patients with inhibitors.

Minimal invasive management of scaphoid fractures: from fresh to nonunion.

The peculiar shape of scaphoid hinders a precise evaluation of its fracture configuration, displacement and accuracy of screw placement. Its tenuous vascular supply risks the complications of delayed union, nonunion and avascular necrosis. Scaphoid is the focus of ligamentous attachment governing carpal kinematics. Preservation of its anatomy and vascularity is critical for normal wrist function. A new fracture classification clearly denoting every fracture type and guiding the management is introduced. The minimal invasive management of different scaphoid fracture conditions, including acute non-displaced and displaced fracture, delayed presentation, and nonunion are discussed. Role of arthroscopy is emphasized. Detailed surgical techniques are shared here.

5-(Dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide as a novel bifunctional antitumor agent and two-photon induced bio-imaging probe.

A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.

Cost minimization analysis to compare activated prothrombin complex concentrate (APCC) and recombinant factor VIIa for haemophilia patients with inhibitors undergoing major orthopaedic surgeries.

Benefits of bypassing agents for maintaining haemostasis in major surgeries have been described in the literature; however, their use has a substantial economic impact. This study assessed the cost of FEIBA, an activated prothrombin complex concentrate and recombinant factor VIIa (rFVIIa) when used in inhibitor patients undergoing major surgeries. After reviewing published literature, a cost minimization model was developed describing dosing regimens recommended and used during major surgeries for FEIBA (pre-operative: 75-100 U kg(-1); postoperative: 75-100 U kg(-1) q 8-12 h days 1-5 and 75-100 U kg(-1) q 12 h days 6-14) and rFVIIa (pre-operative: 90 microg kg(-1); intra-operative: 90 microg kg(-1) q 2 h; postoperative: 90 microg kg(-1) q 2-4 h days 1-5 and 90 microg kg(-1) q 6 h days 6-14). Using a 75 kg patient and US prices, total drug cost was calculated for three scenarios: use of FEIBA or rFVIIa alone and a third case combining rFVIIa pre- and intra-operative and FEIBA throughout a 14-day postoperative period. Dosage amounts of modelled bypassing agents were similar to cases in the literature. Using FEIBA instead of rFVIIa would decrease total drug cost by >50% and save over $400,000 per surgery. Sequential use of both bypassing agents would increase total drug cost by 9% when compared with FEIBA alone, but would remain >40% lower than rFVIIa alone. Univariate sensitivity analyses confirmed robustness of results. As large amounts of bypassing agents are necessary for patients with inhibitors to undergo major surgeries, cost is a major consideration. Use of FEIBA alone or in combination with rFVIIa has emerged as a cost-saving approach.

Ethyl acetate extract of Chinese medicinal herb Sarcandra glabra induces growth inhibition on human leukemic HL-60 cells, associated with cell cycle arrest and up-regulation of pro-apoptotic Bax/Bcl-2 ratio.

Sarcandra glabra (Thunb.) Nakai, colloquially known as Caoshanhu, is a Chinese medicinal herb with reported anti-tumor, anti-inflammatory, anti-viral and non-specific immunoenhancing properties. Although the plant has been clinically used for treating a variety of diseases, its bioactive ingredients are largely unknown and its mode of action has never been investigated. In this study, the anti-tumor property of ethyl acetate (EA) extract of S. glabra was investigated by determining its in vitro growth-inhibitory effects on a panel of human cancer cell lines of different histotypes. Growth inhibition of the EA extract on the cancer cells seemed to be selective, and the leukemic HL-60 was found to be the most responsive after 48 h of treatment (IC50=58 microg/ml). Flow cytometric studies further illustrated that the extract might interfere with DNA replication and thus arrested the cell cycle at S phase in the leukemic cells, followed by DNA fragmentation and loss of phospholipid asymmetry in the plasma membrane after 72 h of treatment. Concurrently, the pro-apoptotic Bax/Bcl-2 ratio was also up-regulated by more than 178% of the control level. All these findings suggested that the extract had initiated apoptosis to kill the leukemic cells. Results from this pioneer study help to establish a scientific foundation for future research and development of the bioactive ingredients in EA extract of S. glabra as efficacious anti-cancer agents.

Progressive decreases in nuclear retinoid receptors during skin squamous carcinogenesis.

Retinoids are essential for normal skin growth, differentiation, and apoptosis and are active pharmacologically in the prevention and treatment of skin cancers and other lesions. Retinoid effects are mediated mainly by retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which act as transcription factors to alter gene expression. Using in situ hybridization, we analyzed the expression of RARs and RXRs in normal sun-exposed skin (n = 85), squamous cell carcinoma (SCC; n = 28), and actinic keratosis [AK (a precursor to SCC); n = 38]. The expressions of five receptors (RAR-alpha and -gamma and RXR-alpha, -beta, and -gamma) were moderate to very strong in normal skin, with higher expressions in spinous and granular layers than in the basal layer. RAR-beta expression was weak or absent in normal and lesion samples. All five receptors expressed in the skin were suppressed progressively from normal skin to premalignant skin (AK) to invasive skin SCC. Specific receptor decreases in lesions relative to normal skin ranged from 75% (RXR-beta) to 96% (RAR-alpha) in SCC and from 37% (RAR-gamma) to 68% (RXR-beta) in AK. The degree of suppression of RXR-alpha and RAR-gamma, the two predominant retinoid receptors in skin, was relatively less for RXR-alpha (58% versus 86%; P = 0.015) and relatively greater for RAR-gamma (37% versus 89%; P = 0.0001) between AK and SCC, suggesting that suppression of RXR-alpha may be an earlier event and expression of RAR-gamma may be a later event of multistep squamous skin carcinogenesis. Our results indicate that suppressed expression of retinoid receptors occurs early (in AK) and is associated with progression of squamous skin carcinogenesis to SCC.

Pentasomy 8 in pediatric myelodysplastic syndrome.

Myelodysplastic syndrome developed in a 2-year-old child with the karyotype revealing the presence of pentasomy 8. The significance of the coexistence of pentasomy 8, tetrasomy 8, and trisomy 8 detected by fluorescence in situ hybridization in his marrow is discussed.

Cigarette smoking and the risk of male factor subfertility: minor association between cotinine in seminal plasma and semen morphology.

OBJECTIVE: To evaluate the impact of cigarette smoking on male factor subfertility and the semen parameters of sperm count, motility, and morphology by questionnaire and determination of the cotinine concentrations in blood and seminal plasma of fertile and subfertile males. DESIGN: Case-control study of 107 fertile and 103 subfertile males who provided a standardized blood and semen specimen and completed a self-administered questionnaire about their smoking habits. SETTING: Outpatient fertility clinic of the University Medical Centre St. Radboud, Nijmegen, The Netherlands. PATIENT(S): One hundred seven fertile and 103 subfertile males. INTERVENTION(S): Vena puncture and semen collection. MAIN OUTCOME MEASURE(S): Blood and seminal plasma cotinine levels in relation to semen parameters. RESULT(S): A higher frequency of cigarette smoking was observed in subfertile males than in fertile males, with an odds ratio of 1.7 (95% confidence interval, 0.9-3.2). The self-reported number of cigarettes smoked per day correlated with the cotinine concentrations in blood and seminal plasma for both groups. A small but statistically significant correlation was found between cotinine concentrations in seminal plasma and the percentage of abnormal sperm morphology, but not for other semen parameters (r(s) = 0.19). CONCLUSION(S): Although the mechanism of the toxicity of cotinine on sperm morphology is not clear, this study indicates only a minor effect of cigarette smoking on male factor subfertility, which is probably due to compounds in cigarette smoke other than nicotine (cotinine).

Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease.

Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9. 4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (Blood. 2000;95:1918-1924)

Male factor subfertility: possible causes and the impact of nutritional factors.

OBJECTIVE: To review possible causes for male factor subfertility with emphasis on nutritional factors such as zinc and folate. DESIGN: A literature search was performed on MEDLINE and via bibliographies of published works. RESULT(S): Many causes for male factor subfertility are described in the literature. Both environmental and genetic factors could play a role. However, the pathogenesis of male factor infertility is poorly understood, including the role of specific micronutrients such as zinc and folate. Both zinc and folate are involved in the synthesis of DNA and RNA. Despite the fact that zinc deficiency leads to several clinical symptoms such as decreased spermatogenesis and impaired male fertility, the exact pathophysiology has not been clarified. CONCLUSION(S): Because most causes of male factor subfertility are unknown, more research is needed. Because male factor subfertility due to nutritional deficiencies is in principle amenable to curative and/or preventive action by supplementation, emphasis should be put on studies on the effect of specific nutrients on male fertility.