Increased prevalence of valgus constitutional alignment subtypes in a South African arthritic population group using the coronal plane alignment of the knee (CPAK) classification.

BACKGROUND: Knee alignment philosophies and patient specific models to improve patient reported outcomes are gaining increasing attention. The coronal plane alignment of the knee (CPAK) classification describes nine knee phenotypes and then proposes surgical alignment strategies to achieve constitutional alignment. The CPAK classification has been validated in Australian, European, Asian and North American population groups. To date no African data has been analyzed using CPAK. METHODS: A total of 344 arthritic patients (608 knees) with appropriate long leg radiographs were classified based on the CPAK type. Measurements included mechanical hip-knee-angle(mHKA), medial proximal tibial angle (mMPTA) and lateral distal femoral angle (mLDFA) and the derived calculations of joint line obliquity (JLO) and arithmetic hip-knee-angle (aHKA). RESULTS: The sample population was 77.9% (n = 268) female with a mean age of 68.4 ± 9.2 years. The most common CPAK types in order were type 3 (n = 174; 28.6%), type 2 (n = 155; 25.5%), type 1 (n = 94; 15.5%) and type 6 (n = 80; 13.2%). The most common limb alignment types were valgus (CPAK types 3,6,9; 41.8%). CONCLUSION: This study, which investigated arthritic patients from a single institution in South Africa, shows a divergence of CPAK phenotypic knee patterns relative to other international studies, with much higher proportions of valgus phenotypes (3 and 6). This regional difference should be further investigated in other South African and African population samples and used to adapt the surgical strategies employed by local surgeons.

The reliability of posterior malleolar ankle fracture assessment: a unique perspective.

AIM: This study aims to elucidate the pathology of PMFs in the South African population, establish correlations between fracture patterns and international classification guidelines and evaluate the interobserver reliability of current classifications. METHODS: A retrospective review was conducted in a multicentre analysis over a one-year period from January 2019 to December 2019 at our institution. Computer tomography scans for foot and ankle injuries were reviewed, and posterior malleolus fractures were included. Pathoanatomical data was collected and analysed according to known classification systems and subsequent treatment modalities evaluated. A panel of observers individually reviewed radiographic data to determine interobserver reliability. RESULTS: A total of 71 patients were included with a mean age of 41 ± 13.4 years (range 18-78) and a female predominant population (69%). A greater proportion of injuries were high energy (23.9%), with significant fragment comminution (53.5%), and half (52.1%) of all injuries were subluxated/dislocated at presentation. A total of 93% of injuries were managed operatively, despite theatre access limitations resulting in significant delays to fixation (19.1 days). Despite good pathoanatomical agreement with most international classifications, interobserver reliability was poor (Krippendorff α-coefficient < 0.667). Inconsistent treatment patterns in operative and non-operative strategies are reported. CONCLUSION: A unique patient population of younger, female individuals incurred posterior malleolar fractures due to higher energy mechanisms of injury. Whilst injury patterns were mostly comparable, significant interobserver variability was noted. Resource limitations, diagnostic challenges, poorly defined and inconsistent treatment strategies, inevitably impact outcomes within the South African population. LEVEL OF EVIDENCE: Level III.

Early outcomes of surgically managed civilian gunshot femur fractures at a level one trauma unit in Cape Town, South Africa: a retrospective review.

PURPOSE: To assess the outcome of surgically fixated femur shaft and distal femur fractures following low-velocity civilian gunshot injuries over a 4-year period. METHODS: A retrospective review was conducted on all patients who sustained femur shaft and distal femur fractures from civilian low-velocity gunshot injuries that required definitive surgical fixation between January 2014 and December 2017. Patient demographics, comorbidities, injury characteristics, duration between injury and surgical fixation and presence of complications were captured. RESULTS: A total of 122 patients (mean age, 29.1 ± 9.5 years) were included. Supracondylar femur fractures (AO 33) accounted for 49% of total injuries, followed by femoral shaft (AO 32) and intra-articular distal femur fractures (AO 33 B & C) with 40% and 11%, respectively. Intramedullary nail fixation was the choice of treatment for femur shaft fractures (49.98%) and supracondylar fractures (63%). Intra-articular injuries were predominantly treated with distal femoral locking plates (85%). Arterial and nerve injuries were the most commonly encountered associated injuries occurring in five patients (4.1%) each. Fracture-related infection was diagnosed in two patients (1.6%). No cases of non-union and compartment syndrome were recorded. CONCLUSION: Femur shaft and supracondylar fractures fixated with intramedullary nails are associated with low complication rates and perfect union rates. Our study suggests that intra-articular distal femur fractures fixated with locking plates and cannulated screws have a high complication rate and poorer surgical outcomes. Non-union and compartment syndrome are rare complications of gunshot femur fractures fixated with either intramedullary nails or locking plates.

Mortality Rates in Femoral Neck Fractures Treated With Arthroplasty in South Africa.

Objectives: To investigate the mortality rate for neck of femur fractures treated with arthroplasty at a tertiary level unit in South Africa and to evaluate the effect of known risk factors for mortality in neck of femur fractures treated with arthroplasty in the South African context. Design: Retrospective cohort study. The main outcome was to determine mortality rates during in hospital stay, at 3 months, 6 months 1 year post surgery. The secondary outcome was to determine factors influencing mortality at 30 days, 6 months and 12 months post-surgery. Results: Mortality rate was 3.3% in hospital, 5.6% at 30 days and 26.7% at 1 year. Age >79, ASA score >3, and cementing of the femur had statistically increased mortality risk (P < .001). Average length of hospital stay was 12.3 ± 5.1 days (range 3.0-41.0 days) with 73% of patients discharged back to pre-hospital home. Conclusion: Mortality rates after femur neck fracture arthroplasty in South Africa are slightly higher at 1 year compared to international data. However, the rates are comparably low during hospital stay, 30 day and at 6 months post-surgical intervals.

Proximal femur anatomy-implant geometry discrepancies.

OBJECTIVES: Due to ongoing concern about femur anatomy-implant mismatches, this cross-sectional study aimed to create a geometric femur profile and used it to identify and quantify possible mismatches between femur anatomy and cephalomedullary nail dimensions. The work further aimed to assess whether patient demographics affect anatomy-implant coherence. METHODS: One hundred skeletally mature complete femur computer tomography (CT) scans were collected and exported to software enabling landmark placement and measures with multiplanar reconstruction techniques. RESULTS: Clinically relevant anatomy-implant discrepancies included the femur neck and shaft axis offset 6.1 ± 1.7 mm (95% CI [5.7-6.4]), femur radius of curvature 1.2 ± 0.3 m (95% CI [1.1-1.2]), femur anteversion 18.8 ± 9.2 (95% CI [16.9-20.6]). The implants reviewed in this study did not compensate for the femur neck and shaft axis offset and had a larger radius of curvature than the studied population. Clinically significant demographic geometry differences were not identified. CONCLUSION: There were discrepancies between femur anatomy and cephalomedullary nail implant design; however, no clinically significant femur feature inconsistency was identified among the demographic subgroups. Due to the identified anatomy-implant discrepancies, including the femur neck and shaft axis offset, we suggest that these measurements be considered for future implant design and surgical technique.

A prospective randomized controlled trial comparing plating augmented with coracoclavicular fixation and hook plate fixation of displaced distal-third clavicle fractures.

BACKGROUND: Two popular methods used to treat distal-third clavicle fractures are the traditional hook plate and the anatomically contoured locking plate. No consensus exists on whether one method is more effective than the other. Therefore, the aim of this study was to compare the efficacy of a traditional hook plate with that of an anatomically contoured locking plate augmented with coracoclavicular fixation in the treatment of distal-third clavicle fractures. METHODS: Enrolled patients were randomly assigned to either the hook plate group (n = 13) or the locking plate group (n = 17). Follow-up assessments (clinical and radiologic) were performed at 6 and 12 months postoperatively. RESULTS: In both groups, union was achieved in 91% of cases at 6 months and 100% at 12 months. No differences in Disabilities of the Arm, Shoulder and Hand (DASH) and Constant-Murley shoulder scores were noted between the hook plate and locking plate groups at 12 months. From 6 to 12 months, DASH scores improved in the hook plate group (P = .007) and Constant-Murley shoulder scores tended to improve (P = .075). Surgical time was longer in the locking plate group than in the hook plate group (P < .001). CONCLUSION: Similar functional outcomes and union rates were achieved in both groups at 12 months postoperatively. However, the improvement in DASH scores in the hook plate group from 6 to 12 months suggests that patients treated with an anatomically contoured locking plate make a quicker recovery than patients treated with a hook plate.

Contemporary management of aseptic diaphyseal tibia non-unions - A systematic review.

INTRODUCTION: Tibia fractures are the most common long bone injuries encountered in the trauma population. The majority are treated successfully but non-union remains a common complication. A systematic review of current evidence regarding the management for aseptic diaphyseal tibial non-unions was undertaken. METHODS: A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), was conducted. RESULTS: A total of 632 publications were screened for inclusion. Full text review of 91 studies resulted in 26 publications being retained for final review. The majority of patients included in the studies either underwent exchange nailing (n=315) or primary intramedullary nailing (n=174) with respective union rates of 88% and 95% being achieved. The highest union rate (97%) was achieved with the use of fine wire external fixation. The major adjuvant treatment modalities were fibula osteotomies (n=372; 41%), fixation dynamization (n=208; 23%) and bone grafting (n=183; 20%). CONCLUSION: The lack of standardization in reporting of outcomes and the diversity of management strategies employed precludes definitive conclusions or recommendations. Further research is required to ascertain the ideal treatment strategy in the management of aseptic tibial diaphyseal non-unions. LEVEL OF EVIDENCE: IV.

Quantitative fit analysis of acromion fracture plating systems using three-dimensional reconstructed scapula fractures - A multi-observer study.

INTRODUCTION: Surgical treatment of displaced acromial and scapula spine fractures may be challenging due to the bony anatomy and variable fracture patterns. This difficulty is accentuated by the limitations of the available scapular plates for fracture fixation. This study compares the quantitative fitting of anatomic scapular plates and clavicle plates, using three-dimensional (3D) printed fractured scapulae. METHODS: Fourteen scapulae with acromion and spine fractures were used for this study. Computerized tomographic (CT) scans of the fractured scapulae were obtained from the Philips picture archiving and communication system (PACS) database of patients admitted to a tertiary teaching hospital in Cape Town, South Africa between 2012 and 2016. The reconstructed scapulae were 3D printed and the anatomical acromion and clavicle plates were templated about the fracture regions. The fit assessment was performed by five observers who classified the plates as no-fit, intermediate fit, and anatomical fit according to the surgical guidelines. RESULTS: The 6-hole anterior clavicle plate performed better than any of the scapular plates as they were able to fit 45.7% of the fractured acromion, including the spine. Among the pre-contoured anatomical scapula plates, both the short and the long acromion plates could fit only 27.3% of the fractured acromion. The intraclass correlation coefficient was 0.965 suggesting excellent consensus among the five observers. CONCLUSION: Clavicle plates were found to be better suited to fit around a scapula fracture in its acromion and spine region.

Randomized Controlled Trial Comparing Silver-Impregnated Fibrous Hydrocolloid Dressings With Silver Sulfadiazine Cream Dressings for the Treatment of Fracture Blisters to Determine Time to Surgical Readiness.

OBJECTIVES: To investigate, in patients with fracture blisters, the time to surgical readiness in those treated with silver-impregnated fibrous hydrocolloid (SFH) dressings compared with those treated with topical silver sulfadiazine (SS) cream and to determine the direct costs associated with both treatments. DESIGN: A single-blind, randomized controlled trial. SETTING: The study was conducted at Tygerberg Hospital, a tertiary care facility, and Worcester Provincial Hospital, a secondary care facility, Western Cape, South Africa. PATIENTS: Patients >18 years of age with one or more fracture blisters overlying fractures requiring surgical fixation were considered for inclusion. MAIN OUTCOME MEASUREMENTS: The main outcome was the time to surgical readiness, after complete re-epithelialization of the affected site, in both groups. The direct cost associated with each treatment and the daily cost associated with hospital stay per day were recorded. RESULTS: At an interim analysis, 70 patients had been enrolled and completed the study protocol with 35 patients per group. Groups were balanced across patient and clinical demographic characteristics. A significant difference of 4 days (95% confidence interval: 2.9-5.1 days, P < 0.001) in the mean time to surgical readiness (SFH group, 5.3 days vs. SS group, 9.3 days) was observed. No difference between the time to surgical procedure as well as the total length of hospital stay between the 2 groups was observed. CONCLUSION: This study reports that SFH dressings are a cost-effective treatment option for the management of fracture blisters evidenced by a significant accelerated time to blister re-epithelialization compared with a commonly described method of SS cream dressings. LEVEL OF EVIDENCE: Therapeutic Level 1. See Instructions for Authors for a complete description of levels of evidence. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Prevalence of Sarcopenia in Older South African Patients Following Surgery for Fragility Fractures of the Hip.

INTRODUCTION: Geriatric patients with a fragility fracture of the hip (FFH) are especially prone to sarcopenia with poor functional outcomes and quality of life. We assessed the prevalence of sarcopenia in older South African patients with FFH. Risk factors for sarcopenia were also investigated. MATERIALS AND METHODS: From August 1 to November 30, 2018, all older patients with FFH were invited to participate. Sarcopenia was diagnosed based on the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Handgrip strength (HGS) and muscle strength were assessed. Muscle quantity was determined by dual-energy X-ray absorptiometry. Demographic information was collected, and 25-hydroxyvitamin D (25[OH]D) status was determined. RESULTS: Of the 100 hip fracture cases, 65 were enrolled, and 52% (34/65) were sarcopenic (women: 62%; men: 38%). HGS accurately identified sarcopenia (sensitivity and specificity: 100%). Patients >80 years of age had a prevalence of sarcopenia twice (18/21 [83%]) that of younger patients (18/44 [36%]). Women with sarcopenia were smaller than those without (weight: p < 0.001; height: p < 0.001; body mass index: p = 0.018). Low 25(OH)D was almost universally present, with median 25(OH)D levels significantly lower in the patients with sarcopenia (27 nmol/L [interquartile range {IQR}: 20-39] vs. 40 nmol/L [IQR: 29-53]). Several risk factors, including advanced age; female sex; a smaller body size, especially among women; limited physical activity; and low 25(OH)D levels, were identified. DISCUSSION: The accuracy of HGS testing in this cohort underscores EWGSOP2's recommendation that muscle strength is key to sarcopenia. Further study and follow-up are required to determine the clinical relevance of sarcopenia among FFH patients. CONCLUSION: The prevalence of sarcopenia in our FFH population is high. Sarcopenia is associated with poor patient outcomes following surgical intervention. Orthopaedic surgeons should therefore be cognizant of the presentation and associated risk of sarcopenia as our patient populations age.

The Apoptosis Pathway and CASP8 Variants Conferring Risk for Acute and Overuse Musculoskeletal Injuries.

Rotator cuff tendinopathy (RCT), anterior cruciate ligament (ACL) ruptures, and carpal tunnel syndrome (CTS), are examples of chronic (RCT and CTS) and acute (ACL ruptures) musculoskeletal soft tissue injuries. These injuries are multifactorial in nature, with several identified intrinsic and extrinsic risk factors. Previous studies have implicated specific sequence variants within genes encoding structural and regulatory components of the extracellular matrix of tendons and/ligaments to predispose individuals to these injuries. An example, includes the association of sequence variants within the apoptotic regulatory gene, caspase-8 (CASP8) with other musculoskeletal injury phenotypes, such as Achilles tendinopathy. The primary aim of this study was, therefore, to investigate previously implicated DNA sequence variants within CASP8: rs3834129 (ins/del) and rs1045485 (G/C), and the rs13113 (T/A) identified using a whole exome sequencing approach, with risk of musculoskeletal injury phenotypes (RCT, ACL ruptures, and CTS) in three independent studies. In addition, the aim was to implicate a CASP8 genomic interval in the modulation of risk of RCT, ACL ruptures, or CTS. It was found that the AA genotype of CASP8 rs13113 (T/A) was independently associated with increased risk for CTS. In addition, it was found that the del-C haplotype (rs3834129-rs1045485) was significantly associated with non-contact ACL ruptures, which is in alignment with previous research findings. Collectively, the results of this study implicate the apoptosis pathway as biologically significant in the underlying pathogenesis of musculoskeletal injury phenotypes. These findings should be repeated in larger sample cohorts and across different populations. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:680-688, 2020.

Complications associated with hexapod circular fixation for acute fractures of the tibia diaphysis: A retrospective descriptive study at a high volume trauma centre.

The use of hexapod circular external fixation in acute tibia fracture care is increasing as more general orthopaedic surgeons are gaining expertise with the use of this treatment modality. Limited data is currently available on the complications that may be encountered with this treatment strategy. AIM: To review the complications and outcomes of acute diaphyseal tibia fractures definitively treated with hexapod circular external fixation at a high volume orthopaedic trauma centre. METHODS: Retrospective review of clinical and radiological data of adult patients with acute diaphyseal tibia fractures treated with hexapod external fixation between 2012 and 2015 at a single centre. RESULTS: A total of 102 diaphyseal fractures were definitively treated with hexapod circular external fixation. Union was achieved in 101 cases with an average time to union of 25.6 weeks. Complications included pin site infection (56%); wound complications (19.67%); osteitis (11.76%); malunion (15.69%) and knee and ankle joint contractures (31.32%). CONCLUSION: Hexapod circular external fixation as definitive treatment of for diaphyseal tibia fractures demonstrates an excellent union rate with acceptable time to union. Complications rates are comparable to that of all fine wire circular fixators. Malalignment in is however a concern, considering that this device enables the surgeon to achieve accurate alignment through gradual deformity correction aided by computer software.

Bony anatomy of the third metacarpal and relationship with the capitate: a computed tomography study.

PURPOSE: The purpose of this study was to accurately establish the anatomical variability of the third metacarpal, its medullary canal, and the relationship with the capitate in the context of high rates of component loosening still seen in total wrist arthroplasty. METHODS: CT scans of a 100 hands (age: 41 ± 14 years (range: 16-71 years); male/female ratio: 53/47) were studied to establish the detailed anatomy of the third metacarpal and the capitate. RESULTS: Although the shape of the third metacarpal and the angles formed with the capitate were highly variable, the third metacarpal length was longer in males (p < 0.001), the proximal cortical bone was thicker (p < 0.001) and the sagittal metacarpal-capitate axis offset was greater (p = 0.01). A relationship was found between the total length of the metacarpal and the distance to the isthmus from the base (r = 0.63; p < 0.0001) which was unaffected by gender. No age-related relationships were significant. CONCLUSION: The anatomy of the third metacarpal and capitate varies considerably more than has been alluded to in current wrist arthroplasty literature. Differences between males and females can likely be attributed to hand size. The distance of the isthmus from the base can be predicted from the total length of the metacarpal with a standard error of 1.9 mm.

Carpal tunnel syndrome: The role of collagen gene variants.

INTRODUCTION: The direct causes of idiopathic carpal tunnel syndrome (CTS) are still unknown. It is suggested that pathology of the tendons and other connective tissue structures within the carpal tunnel may play a role in its aetiology. Variants in genes encoding connective tissue proteins, such as type V collagen, have previously been associated with CTS. Since variants within other collagen genes, such as type I, XI and XII collagen, have previously been associated with modulating the risk of musculoskeletal soft tissue injuries, the aim of this study was to determine whether variants within COL1A1, COL11A1, COL11A2 and COL12A1 were associated with CTS. METHODS: Self-reported Coloured South African participants, with a history of carpal tunnel release surgery (CTS, n=103) and matched control (CON, n=150) participants without any reported history of CTS symptoms were genotyped for COL1A1 rs1800012 (G/T), COL11A1 rs3753841 (T/C), COL11A1 rs1676486 (C/T), COL11A2 rs1799907 (T/A) and COL12A1 rs970547 (A/G). RESULTS: The TT genotype of COL11A1 rs3753841 was significantly over-represented in the CTS group (21.4%) compared to CON group (7.9%, p=0.004). Furthermore, a trend for the T minor allele to be over-represented in the CTS group (p=0.055) with a significant association when only female participants (p=0.036) were investigated was observed. Constructed inferred pseudo-haplotypes including a previously investigated COL5A1 variant, rs71746744 (-/AGGG), suggest gene-gene interactions between COL5A1 and COL11A1 modulate the risk of CTS. DISCUSSION: These findings provide further information of the role of the genetic risk factors and the possible role of variations in collagen fibril composition in the aetiology of CTS. Genetic factors could potential be included in models developed to identify indivisuals at risk of CTS. Strategies that target modifiable risk factors to mitigate the effect of non-modifiable risk factors, such as the genetic risk, could be also developed to reduce incidence and morbidity of CTS.

Matrix metalloproteinase genes on chromosome 11q22 and risk of carpal tunnel syndrome.

Involvement of tendons and/or connective tissue structures in the aetiology of idiopathic carpal tunnel syndrome (CTS) has been proposed. DNA sequence variants within genes encoding structural components of the collagen fibril, the basic structural unit of connective tissue, have been shown to associate with modulating CTS risk. The matrix metalloproteinases (MMPs) play an important role in connective tissue remodelling. Variants within the MMP10, MMP1, MMP3 and MMP12 gene cluster on chromosome 11q22 have been associated with connective tissue injuries. The aim of this study was to investigate whether variants within these MMP genes are associated with CTS. Ninety-seven, self-reported Coloured participants with a history of CTS release surgery and 131 appropriately matched controls were genotyped for MMP10 rs486055 (C/T), MMP1 rs1799750 (G/GG), MMP3 rs679620 (A/G) or MMP12 rs2276109 (A/G) variants. A Pearson's Chi-squared test or a Fisher's exact test was used to determine any significant differences between the genotype distributions or any other categorical data of the groups. An analysis of variance (ANOVA) was used to detect any significant differences between CTS and control groups for continuous data. There were no independent associations between any of the investigated MMP variants and CTS. There were also no significant differences in the relative distributions of the constructed MMP inferred haplotypes between CTS and CON groups. The MMP variants previously associated with other connective tissue injuries were not associated with CTS in this population. These findings do not exclude the possibility that other variants within this locus or other MMP genes are associated with CTS.

Interleukin and growth factor gene variants and risk of carpal tunnel syndrome.

Recent research has identified DNA sequence variants within genes encoding structural components of the collagen fibril, the basic structural unit of tendons, to modify the risk of carpal tunnel syndrome (CTS). Since the expression of these previously associated genes are regulated by cytokine and growth factor signalling pathways, the aim of this study was to determine whether variants within these cell signalling pathway genes, namely interleukin 1ß (IL-1ß), IL-6, interleukin 6 receptor (IL-6R) and vascular endothelial growth factor A(VEGFA), are also associated with CTS. One hundred and three self-reported Coloured participants, with a history of carpal tunnel release surgery (CTS) and 149 matched control participants (CON) without any reported history of CTS symptoms were genotyped for the functional IL-1ß rs16944 (-511C/T), IL-6 rs1800795 (-174G/C), IL-6R rs2228145 (C/A) and VEGFA rs699947 (-2578C/A) variants. Only the IL-6R variant was significantly associated with CTS (p=0.005, OR=0.41, 95% CI 0.22-0.75). When the previously reported associated COL5A1 and BGN variants were included in the analysis, gene-gene interactions were also shown to significantly modulate the risk of CTS. In conclusion, the AA genotype of IL-6R rs2228145 was independently associated with reduced risk of CTS in a South African Coloured population. The IL-6R variant interacted with the previously reported COL5A1 and BGN variants to modulate CTS risk. This highlights that interleukin and growth factor gene variants should also be considered, in addition to the extracellular matrix proteins, for future research in determining the aetiology of CTS.

The COL5A1 gene is associated with increased risk of carpal tunnel syndrome.

The direct causes of idiopathic carpal tunnel syndrome (CTS), a common upper limb entrapment neuropathy, remain unknown. It is however generally accepted that an increase in pressure within the carpal tunnel structure, which contains nine flexor tendons, causes compression of the median nerve. The involvement of these tendons in the aetiology of CTS cannot be excluded. Variants within the collagen, type V, alpha 1 (COL5A1) gene, which encodes for the α1 chain of type V collagen, an important regulator of fibril assembly in tendons, have previously been associated with Achilles tendinopathy. The aim of this study was to determine whether these COL5A1 variants are also associated with CTS. One hundred and three self-reported coloured participants, with a history of carpal tunnel release surgery (CTS) and 150 matched control (CON) participants without any reported history of CTS symptoms were genotyped for the COL5A1 rs13946 (C/T), rs14774622 (C/T)/rs55748801 (G/A) (W/M where W = CG), rs12722 (C/T) and rs71746744 (-/AGGG) variants. The TT genotype of COL5A1 rs13946 was significantly over-represented (p = 0.007) in the CON (69.3 %) compared to that in the CTS (50.6 %) group. When the combined rs14774622/rs55748801 and rs12722 genotypes were analysed, the WW + CC (41.7 %, p = 0.008) and WW + CT (40.3 %, p = 0.009) genotypes were significantly over- and under-represented in the CON group, respectively, when compared to the CTS group (24.5 % WW + CC, 59.2 % WW + CT). Furthermore, the T-W-C (51.2 %, p < 0.001) and C-W-C (15.9 %, p = 0.005) inferred haplotypes were significantly over- and under-represented in the CON compared to the CTS (34.9 % T-W-C, 26.8 % C-W-C). In conclusion, this is the first study to report that variants within the functional COL5A1 3'-untranslated region are associated with the CTS. Further studies are required to replicate these findings.

The BGN and ACAN genes and carpal tunnel syndrome.

The causes of idiopathic carpal tunnel syndrome (CTS) remain unknown and the involvement of the tendons within the carpal tunnel structure in the aetiology of CTS cannot be excluded. Variants within the COL5A1 gene, an important regulator of fibril assembly in tendons, have previously been associated with modulating the risk of CTS. Furthermore, proteoglycans are also important structural components of tendons and variants within the aggrecan gene are associated with musculoskeletal soft tissue injuries. The aim of this study was to determine whether ACAN and BGN variants are associated with CTS. Self-reported Coloured participants (n=99), with a history of CTS release surgery (CTS), and 136 control participants, with no history of CTS symptoms (CON), were genotyped for ACAN rs1516797(G/T) and BGN rs1126499(C/T) variants. The BGN CC genotype was significantly over-represented (p=0.0498; OR=0.545, 95% CI=0.30-0.99) in the CON group (71.8%) versus the CTS (58.1%) group. When the previously reported associated COL5A1 genotypes were included in the analysis, COL5A1 and BGN gene-gene interactions were also shown to significantly modulate the risk of CTS in females. In conclusion this is the first study to report that variants within the BGN gene, independently and by interacting with COL5A1 variants, are associated with CTS. Further studies are required to replicate these findings.

Profiling the approach to the investigation of viral infections in cases of sudden unexpected death in infancy in the Western Cape Province, South Africa.

BACKGROUND: Sudden unexpected death in infancy is one of the main contributory factors to high infant mortality rates world-wide. Several risk factors, including viral infection, have been implicated in SUDI cases, but no single factor has been confirmed as the main cause of death. At the Tygerberg Medico-legal Laboratory, Cape Town, South Africa, investigation of lung tissue for viral infection forms part of an institutional protocol for the examination of cases of sudden unexpected death in infancy. METHODS: Lung tissue from 82 cases of sudden unexpected death in infancy was collected over a 10 month period. Routine shell vial cultures and histological examination of the tissue were performed according to the standard institutional protocol on fresh and formalin-fixed tissue, respectively. In addition, real-time polymerase chain reactions and immunohistochemical staining for adenovirus, cytomegalovirus and respiratory syncytial virus were done on fresh and formalin-fixed lung tissue, respectively. RESULTS: Huge variation was found in the number of positive cases confirmed by shell vial culture, real-time polymerase chain reaction and immunohistochemistry (0, 2 and 0 for adenovirus; 3, 29 and 2 for cytomegalovirus; and 0, 0 and 4 for respiratory syncytial virus, respectively). CONCLUSIONS: In the absence of a National Protocol for investigation of sudden unexpected death in infancy, we conclude that the selection of viruses and routine diagnostic technique included in the institutional investigation protocol might be suboptimal and should be re-evaluated.