Liver complications of haemoglobin H disease in adults.

Haemoglobin H (HbH) disease is a type of non-transfusion-dependent thalassaemia. This cross-sectional study aimed at determining the prevalence and severity of liver iron overload and liver fibrosis in patients with HbH disease. Risk factors for advanced liver fibrosis were also identified. A total of 80 patients were evaluated [median (range) age 53 (24-79) years, male 34%, non-deletional HbH disease 24%]. Patients underwent 'observed' T2-weighted magnetic resonance imaging examination for liver iron concentration (LIC) quantification, and transient elastography for liver stiffness measurement (LSM) and fibrosis staging. In all, 25 patients (31%) had moderate-to-severe liver iron overload (LIC ≥7 mg/g dry weight). The median LIC was higher in non-deletional than in deletional HbH disease (7·8 vs. 2.9 mg/g dry weight, P = 0·002). In all, 16 patients (20%) had advanced liver fibrosis (LSM >7.9 kPa) and seven (9%) out of them had probable cirrhosis (LSM >11.9 kPa). LSM positively correlated with age (R = 0·24, P = 0·03), serum ferritin (R = 0·36, P = 0·001) and LIC (R = 0·28, P = 0·01). In multivariable regression, age ≥65 years [odds ratio (OR) 4·97, 95% confidence interval (CI) 1·52-17·50; P = 0·047] and moderate-to-severe liver iron overload (OR 3·47, 95% CI 1·01-12·14; P = 0·01) were independently associated with advanced liver fibrosis. The findings suggest that regular screening for liver complications should be considered in the management of HbH disease.

A Five-Year Review of Tag Rugby Hand Injuries.

Tag rugby is one of the fastest growing sports in Ireland. It is a soft-contact team game that is loosely based on the rugby league format except players try to remove Velcro tags from their opponents' shorts rather than engage in a typical rugby tackle. The purpose of this study was to examine all tag rugby associated hand injuries over a five-year period in three large tertiary referral hospitals in Ireland. Using the patient corresponding system, 228 patients with hand injury related tag rugby injuries were observed from 2010 to 2015. There were 138 males and 90 females in the study and over 40% of patients required surgery. Most of the patients were young professionals with an average age of 30. Twenty-five patients worked in the financial services whilst there were 23 teachers. Fractures accounted for 124 of the 228 injuries and mallet injuries accounted for 53. Eighty percent of all injuries occurred during the tackle. The mean number of days missed from work was 9.1±13.8 days. These injuries resulted in an average of seven hospital appointments per patient. Considering it is a soft-contact sport, it is surprising the number of hand injuries that we have observed. Although safety measures have been introduced to decrease the number of hand injuries in recent years, there is a need for further improvements. Better player education about seeking prompt medical attention once an injury occurs, coupled with longer shorts worn by players may improve measures for the sport.

An unusual penetrating hand injury from a hurling helmet.

We report on an unusual case of a penetrating injury from a bar from a metal grille from a hurling face protector. The bar impaled the patient's thumb after a collision with a patient. The bar was surgically removed in theatre with minimal injury. The authors highlight the need to ensure that helmets and face protectors are regularly checked, particularly ensuring that the bars have not become detached.

The Irish contribution to the plastic surgery literature: 21 years of publications.

INTRODUCTION: The Republic of Ireland has always had an influence on medicine and has produced many renowned doctors who have helped shape its history. Furthermore, many clinical articles that have originated from Ireland have changed clinical practice throughout the world. The Irish have also had an impact on the plastic surgery literature yet it has never specifically been analyzed before. The purpose of this study was to identify and analyze all papers that have originated from the plastic surgery units in the Republic of Ireland in the medical literature over the past 21 years. METHODOLOGY: Twenty-four well-known plastic surgery, hand surgery and burns journals were selected for this study. By utilizing Scopus, the largest abstract and citation database of peer-reviewed literature, we analyzed each of our chosen 24 journals looking for Irish publications. Each paper was examined for article type, authorship, year of publication, institution of origin and level of evidence. RESULTS: Papers from the Republic of Ireland were published in 20 of the 24 journals over the past 21 years. A total of 245 articles from Ireland were published in the plastic surgery, hand surgery and burns literature over the 21-year period. Of these, 111 were original articles and 73 were case reports. The institution that published the most papers over the past 21 years was University Hospital Galway (66 publications) followed by Cork University Hospital with 54 papers. The journal with the most Irish articles was the Journal of Plastic, Reconstructive and Aesthetic Surgery with 56 papers. 2014 was the year with the most publications (28 papers). Authorship numbers also increased over time as the average number of authors in 1994 was 3.5, whereas it was 5.54 in 2014. DISCUSSION: The number of publications per year continues to increase along with authorship numbers. This mirrors the trend in other specialties. Publications are now no longer required for selection on to a higher surgical training scheme. There is now a fear that the academic output of trainees will decrease as a consequence. To prevent this, each unit must actively support and encourage research activity with their trainees.

A review of sentinel lymph node biopsy for thin melanoma.

INTRODUCTION: Although there is a lack of established survival benefit of sentinel lymph node biopsy (SLNB), this technique has been increasingly applied in the staging of patients with thin (≤1.00 mm) melanoma (T1Nx), without clear supportive evidence. METHODS: We review the guidelines and available literature on the indications and rationale for performing SLNB in thin melanoma. RESULTS: As a consequence of the paucity of evidence of SLNB in thin melanoma, there is considerable variability in the guidelines. It is difficult to define clinicopathologic factors that reliably predict the presence of nodal metastasis. SLNB does not yet inform management in thin melanoma to improve survival outcome. CONCLUSION: Based on available evidence, high risk patients with melanomas between 0.75 and 1.00 mm may be appropriate candidates to be considered for SLN biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy, and the lack of proven survival benefit from any form of surgical nodal staging.

A novel barbed suture tie-over dressing for skin grafts: a comparison with traditional techniques.

INTRODUCTION: Barbed suture devices have a widespread application in plastic surgery. The unidirectional nature of the barbs facilitates a strong grip on tissues and reduces the need to constantly tension the suture manually. We hypothesized that a barbed suture tie-over suture to secure skin grafts would be quicker to perform than traditional tie-overs and would also exert a greater downward pressure on the skin graft. METHODS: Thirty uniform areas of skin were excised from a cadaver. A pressure transducer was placed on the wound bed and covered with the excised skin along with a mineral oil-soaked wool dressing to act as a bolster. Three different sutures were used to secure the graft in place and the pressure was recorded. The tie-over techniques used were the classic silk tie-over, a running Vicryl Rapide™ tie-over and a running barbed tie-over. RESULTS: The barbed tie-over exerted the most downward pressure (82.8 ± 7.3 mmHg) compared to the silk (46 ± 4.85 mmHg) and the Vicryl Rapide™ (18.6 ± 2.4 mmHg). Furthermore, the barbed tie-over was the quickest to perform (1:45 ± 22 s) when compared to the Vicryl Rapide™ (02:57 ± 27 s) and the silk tie-overs (04:26 ± 39 s). CONCLUSION: Barbed sutures are a viable option for securing skin grafts. They are quick to perform and provide significantly improved downward pressure on the skin graft. We feel that this technique would be especially suited to the sole operator as it can be carried out without the need of an assistant.

Flexor tendon repair: a comparative study between a knotless barbed suture repair and a traditional four-strand monofilament suture repair.

We compared the tensile strength of a novel knotless barbed suture method with a traditional four-strand Adelaide technique for flexor tendon repairs. Forty fresh porcine flexor tendons were transected and randomly assigned to one of the repair groups before repair. Biomechanical testing demonstrated that the tensile strengths between both tendon groups were very similar. However, less force was required to create a 2 mm gap in the four-strand repair method compared with the knotless barbed technique. There was a significant reduction in the cross-sectional area in the barbed suture group after repair compared with the Adelaide group. This would create better gliding within the pulley system in vivo and could decrease gapping and tendon rupture.

A bibliometric analysis of the 100 most influential papers in burns.

The importance of a published paper to a particular area is reflected in the quantity of citations obtained from peers. In burns, it is unknown which papers have been the most influential on this specialty. The purpose of our study was to identify the 100 most cited papers in burns and to analyze their characteristics. Twenty-seven journals were chosen for analysis. These included high impact factor scientific journals and journals dedicated to burns and trauma. Only twelve of these journals contributed to the 100 most cited papers in burns and we analyzed each paper individually looking at its subject matter, authorship, article type, institution, country and year of publication. Our citation analysis revealed an interesting mix of clinical and scientific papers that documents the key landmarks in burn care over the past 66 years.

The 100 top-cited classic papers in hand surgery.

The number of citations that a published article has received reflects the importance that paper has on that area of practice. In hand surgery, it is unknown which journal articles are cited most frequently. The purpose of this study was to identify and analyze the characteristics of the top 100 papers in the field of hand surgery. The 100 most cited papers were identified in the following journals; the Journal of Hand Surgery (American volume), the Journal of Hand Surgery (European volume), the Journal of Hand Surgery (British and European volume), The Scandinavian Journal of Plastic and Reconstructive and Hand Surgery, Hand Clinics, and the Journal of Plastic Surgery and Hand Surgery. The articles were ranked in order of the number of citations received. These classic 100 papers were analyzed for article type, their journal distribution, as well as geographic and institutional origin.

Second to fourth digit ratio confirms aggressive tendencies in patients with boxers fractures.

BACKGROUND: Upper limb second to fourth digit ratio (2D:4D) has been shown to be dependent on prenatal androgen exposure. A longer relative fourth digit to second digit is indicative of increased intrauterine testosterone exposure prenatally and the converse is also true for oestrogen exposure. The 2D:4D ratio has implications in the sporting, academic, financial and sexual arenas. The purpose of this study was to examine the association between smaller finger length ratios (2D:4D) and boxers fractures, in both men and women, by comparing the 2D:4D ratios in 150 boxers fractures and comparing them to matched controls. Boxers fractures are an injury classically incurred during acts of aggression and we postulated that this cohort of patients would have a smaller 2D:4D ratio in comparison to the normal population mean ratio. METHODS: One hundred and fifty radiographs from patients with boxers fractures secondary to aggressive actions were analysed and the 2D:4D ratio was calculated. A further 150 X-rays from patients not involved in aggressive activities were used as a control group and the 2D:4D ratio was calculated in the same manner. We then performed statistical analysis to compare the 2D:4D ratios between our two groups. RESULTS: As predicted, the 2D:4D in males was smaller than females in all of the groups. However, our results showed that those presenting with a boxers fracture due to an aggression related injury had a statistically significant smaller 2D:4D ratio when compared to the normal population. CONCLUSION: Boxers fractures are injuries that typically occur from an aggressive act. It is well documented that a low 2D:4D ratio is reflective of an increased prenatal exposure to androgens, particularly testosterone. We have shown that boxers fractures are associated with a smaller 2D:4D ratio than the normal population, thus suggesting that persons exposed to high levels of prenatal androgens are more likely to exhibit aggressive tendencies in adulthood. Our results suggest that smaller digit ratios may predict a predisposition to acts of aggression, and as such result in an increased likelihood of sustaining an injury such as a boxers fracture. This relationship seems to be present independently of gender.

Intrathecal chemotherapy for hematologic malignancies: drugs and toxicities.

Intrathecal (IT) chemotherapy is an important component of the prophylaxis or treatment of hematologic malignancies in the central nervous system (CNS), especially in patients with acute lymphoblastic leukemia and aggressive lymphomas. Different regimens of IT chemotherapies have been formulated, often in conjunction with systemic high-dose chemotherapy leading to penetration of the drugs into the cerebrospinal fluid (CSF). The three commonest IT drugs are methotrexate, cytosine arabinoside (Ara-C), and corticosteroids. The CSF half-lives of methotrexate and Ara-C are much prolonged, a factor to be considered if these drugs are also administered systemically in high doses. Neurotoxicities attributed to IT chemotherapy have been reported, including spinal cord lesions, seizures, and encephalopathy. Spinal cord lesions, manifesting as tetraplegia, paraplegia, and cauda equina syndrome, are the commonest neurotoxicity. It is mostly related to combined IT methotrexate and Ara-C, or Ara-C as the sole IT agent when given at high doses or as a slow-release preparation. Cord lesions rarely recover and patients are left with motor deficits, bowel and urinary disabilities. Seizures and encephalopathy are reported in relatively fewer patients, with variable manifestations and prognosis. Knowledge of the pharmacokinetics, dosing schedules and potential toxicities of IT chemotherapeutic drugs is important in the design of CNS prophylaxis and treatment in hematologic malignancies.

4q loss is potentially an important genetic event in MM tumorigenesis: identification of a tumor suppressor gene regulated by promoter methylation at 4q13.3, platelet factor 4.

In this study, we have elucidated the chromosomal imbalances in the multistep pathogenesis and delineated several critical tumor suppressor gene (TSG) loci in multiple myeloma (MM). By using comparative genomic hybridization, allelotyping, and multicolor interphase fluorescence in situ hybridization, 5 MM cell lines and bone marrow CD138+ plasma cells from 88 Chinese patients with monoclonal gammopathy of undetermined significance (MGUS) and early and advanced stages of MM were investigated. In all MGUS and MM samples, chromosome copy number abnormalities were detected. A higher number of chromosomal imbalances and specific genetic alterations are involved in MGUS to MM transition (-6q, +3p, and +1p) and MM progression (+2p and +9q). In addition to -13q, we first found high frequencies (42% to 46%) of -4q involving high percentages (70% to 74%) of clonal plasma cells in both MGUS and MM, suggesting that inactivation of TSG in this region is also a potentially critical genetic event in MM tumorigenesis. By high-resolution allelotyping, we defined a common deletion region on 4q13.3 and found that a candidate TSG, platelet factor 4, was frequently silenced by promoter hypermethylation in MM (15 of 28) and MM cell lines (5 of 5). These data have opened up a new approach in the molecular targeting therapy and provide novel insights into MM tumorigenesis.

Use of the oral chelator deferiprone in the treatment of iron overload in patients with Hb H disease.

Seventeen non-transfusion-dependent Chinese haemoglobin H (Hb H) disease patients (age 29-76 years) with serum ferritin >900 microg/l were treated with deferiprone for up to 18 months. One patient withdrew and data from 16 patients were analysed. Sixteen other Hb H patients with ferritin <900 microg/l, matched for age and genotype, acted as controls. Treatment was well tolerated except for mild arthralgia. Serum ferritin fell with treatment, reaching significance at 6 and 18 months (from 1492.3 +/- 901.4 to 519.4 +/- 405.4 microg/l at 18 months, P = 0.0008). Nine of 16 patients had levels below 397 microg/l before 18 months. Serum ferritin remained stable 6 months after stopping treatment. In contrast, there was no change in ferritin levels in the control group. Magnetic resonance imaging was used for measurement of liver iron content. Spin echo T(1)-signal intensity ratio (T(1)-SIR) and gradient echo T(2)-signal intensity ratio (T(2)-SIR) increased with treatment. T(2)-SIR rose from 0.17 +/- 0.08 pretreatment to 0.58 +/- 0.50 at 2 years (P = 0.0055). Improvement occurred in 12 of 16 patients, reaching normal in three patients. Using echocardiography, peak early diastolic : late diastolic blood flow (E/A) remained unchanged with treatment, but isovolumic relaxation time (IVRT) was prolonged at 2 years indicating mild impairment of diastolic function. All systolic function parameters were normal. A longer treatment period is desirable to demonstrate improvement in cardiac function.

Alterations of RAS signalling in Chinese multiple myeloma patients: absent BRAF and rare RAS mutations, but frequent inactivation of RASSF1A by transcriptional silencing or expression of a non-functional variant transcript.

The methylation status, mutation and expression of RASSF1A, and mutations of RAS and BRAF were studied in 52 patients with multiple myeloma (MM), one plasma cell leukaemia (PCL) patient and four MM-derived cell lines. Aberrant methylation of RASSF1A was found in nine of 32 MM patients and in one of four MM cell lines (U266), where the associated loss of transcription was reversible by demethylation treatment. RASSF1A transcription was further investigated on anti-CD138-sorted plasma cell-enriched bone marrow samples from 10 MM, one PCL and three reactive plasmacytosis patients. While the wild-type RASSF1A transcript was detected in all three reactive plasmacytosis and the PCL samples, we found no detectable wild-type transcripts in six of 10 MM samples studied. In two MM samples, only the non-functional variant transcript was detected, whereas the other four showed loss of transcription. In great contrast to western data, RAS mutations were identified in only four of 31 (13%) MM patients. While no RASSF1A or BRAF mutation (V599E) was detected in any of the primary MM studied (n = 21), the latter was found in the U266 cell line. Taken together, these data indicate that alterations of RAS signalling are critical in MM pathogenesis. In our current studies of Chinese MM patients, these alterations involved frequent RASSF1A inactivation (60%) as a result of transcriptional silencing or expression of a non-functional variant transcript.