Comparison of outcomes from tunnelled femorally inserted central catheters and peripherally inserted central catheters: a propensity score-matched cohort study.

OBJECTIVES: To compare catheter-related outcomes of individuals who received a tunnelled femorally inserted central catheter (tFICC) with those who received a peripherally inserted central catheter (PICC) in the upper extremities. DESIGN: A propensity-score matched cohort study. SETTING: A 980-bed tertiary referral hospital in South West Sydney, Australia. PARTICIPANTS: In-patients referred to the hospital central venous access service for the insertion of a central venous access device. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome of interest was the incidence of all-cause catheter failure. Secondary outcomes included the rates of catheters removed because of suspected or confirmed catheter-associated infection, catheter dwell and confirmed upper or lower extremity deep vein thrombosis (DVT). RESULTS: The overall rate of all-cause catheter failure in the matched tFICC and PICC cohort was 2.4/1000 catheter days (95% CI 1.1 to 4.4) and 3.0/1000 catheter days (95% CI 2.3 to 3.9), respectively, and when compared, no difference was observed (difference -0.63/1000 catheter days, 95% CI -2.32 to 1.06). We found no differences in catheter dwell (mean difference of 14.2 days, 95% CI -6.6 to 35.0, p=0.910); or in the cumulative probability of failure between the two groups within the first month of dwell (p=0.358). No significant differences were observed in the rate of catheters requiring removal for confirmed central line-associated bloodstream infection (difference 0.13/1000 catheter day, 95% CI -0.36 to 0.63, p=0.896). Similarly, no significant differences were found between the groups for confirmed catheter-related DVT (difference -0.11 per 1000 catheter days, 95% CI -0.26 to 0.04, p=1.00). CONCLUSION: There were no differences in catheter-related outcomes between the matched cohort of tFICC and PICC patients, suggesting that tFICCs are a possible alternative for vascular access when the veins of the upper extremities or thoracic region are not viable for catheterisation.

Resistance Mutation Patterns among HIV-1-Infected Children and Features of the Program for Prevention of Mother-to-Child Transmission in Vietnam's Central Highlands and Southern Regions, 2017-2021.

The Vietnam Ministry of Health (MOH) has intensified efforts in its aim to eliminate AIDS by 2030. Expanding the program for prevention of mother-to-child transmission (PMTCT) is a significant step towards achieving this goal. However, there are still HIV-exposed children who do not have access to PMTCT services, and some who have participated in the program but still contracted HIV. This study focused on assessing the prevalence and profile of HIV mutations among children under 18 months of age who had recently tested positive for HIV, while gaining insights into the implementation of early infant diagnostic (EID) tests. Between 2017 and 2021, 3.43% of 5854 collected dry blood spot (DBS) specimens from Vietnam's Central and Southern regions showed positive EID results. This study identified a high prevalence of resistance mutations in children, totaling 62.9% (95% CI: 53.5-72.3). The highest prevalence of mutations was observed for NNRTIs, with 57.1% (95% CI: 47.5-66.8). Common mutations included Y181C and K103N (NNRTI resistance), M184I/V (NRTI resistance), and no major mutations for PI. The percentage of children with any resistance mutation was significantly higher among those who received PMTCT interventions (69.2%; 95% CI: 50.5-92.6%) compared with those without PMTCT (45.0%; 95% CI: 26.7-71.1%) with χ2 = 6.06, p = 0.0138, and OR = 2.75 (95% CI: 1.13-6.74). Mutation profiles revealed that polymorphic mutations could be present regardless of whether PMTCT interventions were implemented or not. However, non-polymorphic drug resistance mutations were predominantly observed in children who received PMTCT measures. Regarding PMTCT program characteristics, this study highlights the issue of late access to HIV testing for both mothers and their infected children. Statistical differences were observed between PMTCT and non-PMTCT children. The proportion of late detection of HIV infection and breastfeeding rates were significantly higher among non-PMTCT children (p < 0.05). Comparative analysis between children with low viral load (≤200 copies/mL) and high viral load (>200 copies/mL) showed significant differences between the mothers' current ART regimens (p = 0.029) and the ARV prophylaxis regimen for children (p = 0.016). These findings emphasize the need for comprehensive surveillance to assess the effectiveness of the PMTCT program, including potential transmission of HIV drug-resistance mutations from mothers to children in Vietnam.

Effect of Tibial Component Misalignment on the Lower Limb Joint Kinematics During Squat.

The component orientation of the total knee replacement is critical to surgical outcomes. There have been many studies focused on knee movement for different component rotations. However, the effect of component misalignment on a dynamic movement, especially which requires high knee flexion, is not widely studied. The aim of this study is to investigate the effect of tibial component misalignment on a squat motion by predictive simulation. Squat motions with different replacement component alignments were predicted by formulating an optimal control problem. The result indicates that component misalignment on coronal and horizontal planes reduces peak joint flexion angles and the external rotation on the horizontal plane has the most negative impact. Misalignment in external rotation resulted in the greatest reduction of peak joint flexion angles. The simulation was validated by comparison with experimental data, which showed a high level of correlation with the predicted motion.Clinical relevance- The predictive simulation presented in this study can predict the dynamic post-surgery movement of TKR. It has the potential to help surgeons and clinicians at the preoperative planning stage.

Acceptability, feasibility, and accuracy of blood-based HIV self-testing: A cross-sectional study in Ho Chi Minh City, Vietnam.

HIV self-testing (HIVST) is an effective approach to increase testing uptake. While oral fluid-based HIVST has been rapidly scaled, use of blood-based HIVST remains limited. We evaluated the acceptability, feasibility, and accuracy of blood-based HIVST among lay users in Ho Chi Minh City (HCMC), Vietnam. We conducted a cross-sectional study among HIV testing clients at the HCMC Pasteur Institute from March 2019 to October 2020. Participants received one HIVST kit and performed the test in front of an observer. The observer used product-specific questionnaires to collect information on the HIVST process, test results, experiences. The participants' interpretations of HIVST results were compared to health staff's interpretations and gold standard laboratory EIA reference tests. Of 2,399 participants who accepted HIVST, 64.7% were men, 62.1% aged 25-49 years, 53.5% had a higher education level, 41.4% were employed, and 35.6% were first-time testers. The vast majority (94.4%) desired to use the test in the future, and 93.9% reported willingness to recommend the test. The majority (90.8%) of participants successfully completed the self-test. One factor associated with successful completion was higher education level (aOR = 1.85; 95% CI: 1.32-2.61); while participants self-testing with SURE CHECK (aOR = 0.21; 95% CI: 0.12-0.37), INSTI (aOR = 0.23; 95% CI: 0.13-0.39), and BioSURE (aOR = 0.29; 95% CI: 0.17-0.51) or being unemployed, retired, or doing housework (aOR = 0.45; 95% CI: 0.25-0.82) were less likely to perform the test successfully. Agreement of positive and negative HIVST results as interpreted by participants and health staff was high (98.1% and 99.9%, respectively). Sensitivity and specificity of the evaluated HIVST were 96.43% (95% CI: 93.62-99.23) and 99.9% (95% CI: 99.75-100), respectively. Our findings confirm that blood-based HIVST is highly acceptable, feasible, and accurate. This evidence informs scale-up of HIVST to increase uptake of essential HIV prevention and treatment services.

Kinematic alignment in total knee arthroplasty: a five-year prospective, multicentre, survivorship study.

AIMS: The mid-term results of kinematic alignment (KA) for total knee arthroplasty (TKA) using image derived instrumentation (IDI) have not been reported in detail, and questions remain regarding ligamentous stability and revisions. This paper aims to address the following: 1) what is the distribution of alignment of KA TKAs using IDI; 2) is a TKA alignment category associated with increased risk of failure or poor patient outcomes; 3) does extending limb alignment lead to changes in soft-tissue laxity; and 4) what is the five-year survivorship and outcomes of KA TKA using IDI? METHODS: A prospective, multicentre, trial enrolled 100 patients undergoing KA TKA using IDI, with follow-up to five years. Alignment measures were conducted pre- and postoperatively to assess constitutional alignment and final implant position. Patient-reported outcome measures (PROMs) of pain and function were also included. The Australian Orthopaedic Association National Joint Arthroplasty Registry was used to assess survivorship. RESULTS: The postoperative HKA distribution varied from 9° varus to 11° valgus. All PROMs showed statistical improvements at one year (p < 0.001), with further improvements at five years for Knee Osteoarthritis Outcome Score symptoms (p = 0.041) and Forgotten Joint Score (p = 0.011). Correlation analysis showed no difference (p = 0.610) between the hip-knee-ankle and joint line congruence angle at one and five years. Sub-group analysis showed no difference in PROMs for patients placed within 3° of neutral compared to those placed > 3°. There were no revisions for tibial loosening; however, there were reports of a higher incidence of poor patella tracking and patellofemoral stiffness. CONCLUSION: PROMs were not impacted by postoperative alignment category. Ligamentous stability was maintained at five years with joint line obliquity. There were no revisions for tibial loosening despite a significant portion of tibiae placed in varus; however, KA executed with IDI resulted in a higher than anticipated rate of patella complications.Cite this article: Bone Jt Open 2022;3(8):656-665.

Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Predictors of Treatment Success After Periprosthetic Joint Infection: 24-Month Follow up From a Multicenter Prospective Observational Cohort Study of 653 Patients.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating condition and there is a lack of evidence to guide its management. We hypothesized that treatment success is independently associated with modifiable variables in surgical and antibiotic management. METHODS: The is a prospective, observational study at 27 hospitals across Australia and New Zealand. Newly diagnosed large joint PJIs were eligible. Data were collected at baseline and at 3, 12, and 24 months. The main outcome measures at 24 months were clinical cure (defined as all of the following: alive, absence of clinical or microbiological evidence of infection, and not requiring ongoing antibiotic therapy) and treatment success (clinical cure plus index prosthesis still in place). RESULTS: Twenty-four-month outcome data were available for 653 patients. Overall, 449 patients (69%) experienced clinical cure and 350 (54%) had treatment success. The most common treatment strategy was debridement and implant retention (DAIR), with success rates highest in early postimplant infections (119 of 160, 74%) and lower in late acute (132 of 267, 49%) and chronic (63 of 142, 44%) infections. Selected comorbidities, knee joint, and Staphylococcus aureus infections were independently associated with treatment failure, but antibiotic choice and duration (including rifampicin use) and extent of debridement were not. CONCLUSIONS: Treatment success in PJI is associated with (1) selecting the appropriate treatment strategy and (2) nonmodifiable patient and infection factors. Interdisciplinary decision making that matches an individual patient to an appropriate management strategy is a critical step for PJI management. Randomized controlled trials are needed to determine the role of rifampicin in patients managed with DAIR and the optimal surgical strategy for late-acute PJI.

Increases in both HIV and syphilis among men who have sex with men in Vietnam: Urgent need for comprehensive responses.

The objective of this study was to determine the temporal trends and factors associated with HIV and syphilis infection among men who have sex with men (MSM) in southern Vietnam. Data from the 2014-2018 national HIV sentinel surveillance of MSM aged 16 years or older were collected from three provinces, including An Giang (N = 761), Can Tho (N = 900), and Ho Chi Minh City (N = 1426), and examined for changes in prevalence rates of HIV and syphilis and risk behaviors over time. Multivariate logistic regression was performed to assess the trends and correlates of HIV and syphilis infections among MSM. There were upward trends for HIV (9.5% in 2014 to 14.2% in 2018, p-trend<0.01), syphilis (4.9% in 2014 to 8.0% 2018, p-trend<0.01), and HIV/syphilis co-infection (1.9% in 2014 to 3.1% in 2018, p-trend=0.01). Factors associated with HIV infection included place of residence, early sexual debut, consistent condom use and not engaging in anal sex during the past month, not knowing one's HIV test results, having ever injected drugs, and having active syphilis. Additionally, early sexual debut and being HIV positive were associated with syphilis infection. Rising prevalences of these infections among MSM suggests an urgent need for comprehensive intervention packages for HIV/STI prevention.

Deep-learning-aided forward optical coherence tomography endoscope for percutaneous nephrostomy guidance.

Percutaneous renal access is the critical initial step in many medical settings. In order to obtain the best surgical outcome with minimum patient morbidity, an improved method for access to the renal calyx is needed. In our study, we built a forward-view optical coherence tomography (OCT) endoscopic system for percutaneous nephrostomy (PCN) guidance. Porcine kidneys were imaged in our experiment to demonstrate the feasibility of the imaging system. Three tissue types of porcine kidneys (renal cortex, medulla, and calyx) can be clearly distinguished due to the morphological and tissue differences from the OCT endoscopic images. To further improve the guidance efficacy and reduce the learning burden of the clinical doctors, a deep-learning-based computer aided diagnosis platform was developed to automatically classify the OCT images by the renal tissue types. Convolutional neural networks (CNN) were developed with labeled OCT images based on the ResNet34, MobileNetv2 and ResNet50 architectures. Nested cross-validation and testing was used to benchmark the classification performance with uncertainty quantification over 10 kidneys, which demonstrated robust performance over substantial biological variability among kidneys. ResNet50-based CNN models achieved an average classification accuracy of 82.6%±3.0%. The classification precisions were 79%±4% for cortex, 85%±6% for medulla, and 91%±5% for calyx and the classification recalls were 68%±11% for cortex, 91%±4% for medulla, and 89%±3% for calyx. Interpretation of the CNN predictions showed the discriminative characteristics in the OCT images of the three renal tissue types. The results validated the technical feasibility of using this novel imaging platform to automatically recognize the images of renal tissue structures ahead of the PCN needle in PCN surgery.

Application of Fibre Bragg Grating Sensors in Strain Monitoring and Fracture Recovery of Human Femur Bone.

Fibre Bragg Grating (FBG) sensors are gaining popularity in biomedical engineering. However, specific standards for in vivo testing for their use are absolutely limited. In this study, in vitro experimental tests were performed to investigate the behaviors and applications of gratings attached to intact and fractured thighbone for a range of compression loading (<300 N) based around some usual daily activities. The wavelength shifts and the corresponding strain sensitivities of the FBG sensors were measured to determine their effectiveness in monitoring the femoral fracture healing process. Four different arrangements of FBG sensors were selected to measure strains at different critical locations on the femoral sawbones surface. Data obtained for intact and plated sawbones were compared using both embedded longitudinal and coiled FBG arrays. Strains were measured close to the fracture, posterior linea aspera and popliteal surface areas, as well as at the proximal and distal ends of the synthetic femur; their responses are discussed herein. The gratings on the longitudinally secured FBG arrays were found to provide high levels of sensitivity and precise measurements, even for relatively small loads (<100 N). Nevertheless, embedding angled FBG sensors is essential to measure the strain generated by applied torque on the femur bone. The maximum recorded strain of the plated femur was 503.97 µÎµ for longitudinal and -274.97 µÎµ for coiled FBG arrays, respectively. These project results are important to configure effective arrangements and orientations of FBG sensors with respect to fracture position and fixation implant for future in vivo experiments.

Novel implant for peri-prosthetic proximal tibia fractures.

BACKGROUND: Repair of peri-prosthetic proximal tibia fractures is very challenging in patients with a total knee replacement or arthroplasty. The tibial component of the knee implant severely restricts the fixation points of the tibial implant to repair peri-prosthetic fractures. A novel implant has been designed with an extended flange over the anterior of tibial condyle to provide additional points of fixation, overcoming limitations of existing generic locking plates used for proximal tibia fractures. Furthermore, the screws fixed through the extended flange provide additional support to prevent the problem of subsidence of tibial component of knee implant. METHODS: The design methodology involved extraction of bone data from CT scans into a flexible CAD format, implant design and structural evaluation and optimisation using FEM as well as prototype development and manufacture by selective laser melting 3D printing technology with Ti6Al4 V powder. RESULTS: A prototype tibia implant was developed based on a patient-specific bone structure, which was regenerated from the CT images of patient's tibia. The design is described in detail and being applied to fit up to 80% of patients, for both left and right sides based on the average dimensions and shape of the bone structure from a wide range of CT images. CONCLUSION: A novel tibial implant has been developed to repair peri-prosthetic proximal tibia fractures which overcomes significant constraints from the tibial component of existing knee implant.

Hip fractures in young adults: a retrospective cross-sectional study of characteristics, injury mechanism, risk factors, complications and follow-up.

This study characterises risk factors, complications and follow-up of minimal trauma hip fractures in young adults, adding to limited information examining the management framework. This group have severe systemic disease and significant risk of post-operative complications and subsequent fractures. Improved medical referral pathways enable management of osteoporosis and comorbid diseases. AIMS: There is a paucity of literature examining minimal trauma hip fractures in young adults, despite extensive management guidelines for older patients. This study aims to characterise risk factors, complications and follow-up of hip fractures to guide management pathways. METHODS: This is a retrospective study of patients presenting with hip fracture to a single institution from 2009 to 2015. Hip fractures were identified using ICD-10 codes and clinical information documented from medical records. Patients were categorised into minimal trauma (MTF) and high-energy fracture (HEF) groups based on mechanism of injury. RESULTS: Of 2512 patients admitted with hip fracture, 2.5% (n = 62) were aged 15-49 years. Two patients were excluded with pathological fractures, and seven were excluded with no recorded mechanism of injury. MTF occurred in 43 patients and 10 sustained HEF. These groups had similar demographics, fracture locations and treatments. The MTF group had higher American Society of Anaesthesiologists scores (MTF 2.44 ± 0.9; HEF 1.43 ± 0.5; p = 0.025) and higher rates of chronic endocrine disease (MTF 34.9%; HEF 0%; p = 0.046). Rates of post-operative surgical (MTF 24.0%; HEF 12.5%) and medical complications (MTF 27.8%; HEF 12.5%) were high in MTF patients. Subsequent fractures occurred in five (13.9%) MTF patients during the study period compared with none in the HEF group. Only 16 (44.4%) of the MTF patients were referred to endocrine care. CONCLUSION: Young adults with MTF of the hip have more severe systemic disease and are at risk of post-operative complications and subsequent fractures. Referral of patients to endocrine care is recommended to manage osteoporosis and comorbid diseases.

Variation in Prosthetic Joint Infection and treatment strategies during 4.5 years of follow-up after primary joint arthroplasty using administrative data of 41397 patients across Australian, European and United States hospitals.

BACKGROUND: To identify best practices and quality improvement initiatives, we aimed to assess whether the incidence of Periprosthetic Joint Infection (PJI) and treatment strategies differed across patients treated in Australian, European and United States (US) hospitals. METHODS: Routinely collected administrative data for 41397 patients undergoing a primary total hip or knee arthroplasty between July 2007-December 2010 across 22 hospitals were included. Patients were followed for 2 years looking for PJI occurrence, defined as early (within 4 weeks) and late PJI, and surgical treatment during 2.5 years after PJI diagnosis. Logistic and Poisson regression models were used to test for differences in PJI occurrence and treatment strategies across the three geographical regions, adjusted for age, sex, joint and Elixhauser comorbidity groups. RESULTS: PJI occurrence varied from 1.4% in European to 1.7% in Australian patients, which were significantly higher than US patients after adjustment for patient characteristics (OR 1.24 [1.01-1.52] and 1.40 [1.03-1.91] respectively). Early PJIs varied between 0.3% in European to 0.6% in Australian patients, but adjusted rates were similar. Revision following PJI was significantly lower in Australian than in US patients (OR 0.46 [0.25-0.86]) as were the total number of revisions (RR 0.51 [0.36-0.71]) and number of surgical procedures (RR 0.60 [0.44-0.81]) used to treat PJI. CONCLUSION: The overall PJI rate was significantly higher in Australian patients, but fewer procedures were needed to treat these PJIs. Future research should reveal whether this reflects PJIs caught earlier or less severe when diagnosed, and whether this is associated with the longer length of stay after primary arthroplasty in Australian hospitals.

An enhanced recovery after surgery program for hip and knee arthroplasty.

OBJECTIVE: To institute and evaluate the benefits of an enhanced recovery after surgery (ERAS) program across three hospitals in Victoria. DESIGN, SETTING AND PARTICIPANTS: We used a before-and-after quality improvement study design consisting of three phases: pre-ERAS program data collection from March to September 2012; ERAS training and implementation during September 2012; and change performance measurement following ERAS implementation from October 2012 to May 2013. MAIN OUTCOME MEASURES: The primary end point was duration of hospital stay after knee or hip arthroplasty. Secondary end points were adherence to the ERAS bundle, and process and patient recovery characteristics. RESULTS: We enrolled 412 patients to the pre-ERAS (existing-practice) phase and compared them with 297 patients in the ERAS phase. For ERAS patients, compared with existing-practice patients, hospital stay was reduced (geometric mean, 5.3 [SD, 1.6] v 4.9 [SD, 1.6] days; P < 0.001) and there was a significant improvement in the proportion of patients ready for discharge on Day 3 after surgery (41% v 59%; P < 0.001). The most common reason for delayed discharge was patients waiting for review or access to rehabilitation services. There were markedly improved indicators of processes and outcomes of care, including improved patient education, reduced fasting times, less blood loss, better analgesia, earlier ambulation and improved overall quality of recovery. CONCLUSION: We found that an ERAS program could be successfully implemented in elective joint arthroplasty, leading to a shorter duration of hospital stay. We recommend this orthopaedic ERAS pathway.

TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport.

Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. Both the N- and C-terminal domains are oriented towards the cytoplasm. Immunofluorescence analysis supports that TMEM115 is enriched in the Golgi cisternae. Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. Co-immunoprecipitation and in vitro binding experiments reveals that TMEM115 interacts with the COG complex, and might self-interact to form dimers or oligomers. A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex.

Detection of cytomegalovirus DNA on dried blood spots collected from infants infected with HIV: an in-house method adaptable in resource-limited settings.

In countries with limited resources, infants infected with HIV are highly exposed to CMV co-infection which probably represents a major risk factor for disease progression in this population. This study aimed to evaluate the performance of a low cost CMV DNA extraction method from DBS and the feasibility of its implementation in laboratories of 4 countries with limited resources. DNA was extracted from DBS with a cationic resin (chelex 100) and amplified with an "in house" real time CMV PCR. Dilutions of a quantified whole blood sample were spotted on paper to evaluate the 95% detection limit. A DBS quality control panel was analyzed in all laboratories. CMV PCR was compared between DBS and liquid whole blood (gold standard) in 2 populations: 418 transplanted patients and 59 infants infected with HIV (median age of 2 months). The CMV PCR 95% detection limit in DBS was 3.87 log10 copies/mL. Its positive and negative predictive values for CMV diagnosis in infants infected with HIV were 100% and 87.5% respectively. Quality control panels gave consistent qualitative results in all laboratories. This assay had high predictive values for CMV diagnosis in infants infected with HIV and its implementation in resource-limited countries with limited resources is feasible.

Metatarsus adductus: development of a non-surgical treatment pathway.

Metatarsus adductus (MA) occurs in one to two cases per 1000 births and is the most common congenital foot deformity in newborns. The appearance is that of a curved or adducted forefoot with a normal hindfoot. A systematic literature review was conducted to answer the following question: For a child who presents with MA, what is the most evidence-based conservative treatment option? Thirteen articles were reviewed using the National Health and Medical Research Council levels of evidence and guidelines for clinical practice. Conservative treatment options reported on included the following: no treatment, stretching, splinting, serial casting, sitting and sleeping positions and footwear/orthotics. There was strong evidence supporting no treatment in the case of flexible MA. Some limited evidence was found for the treatment of semi-rigid MA. Clinicians should use these recommendations together with clinical experience when advising parents on treatment of MA.

Intra-operative reliability of ShapeMatch cutting guide placement in total knee arthroplasty.

Custom cutting guides based on pre-operative imaging have been introduced for total knee arthroplasty (TKA). The aim of this prospective cohort study was to assess the reliability of repeated placement of custom cutting guides by multiple surgeons in a group of patients undergoing TKA. Custom cutting guides (ShapeMatch®, Stryker Orthopaedics) were designed from pre-operative MRI scans. The treating surgeon placed each guide on the femur and tibia of each patient three times without pinning the block. The three-dimensional position and orientation of the guide was measured for each repetition using a computer navigation system. The surgeon was blinded to the navigation system display. Data from 24 patients and 6 surgeons were analyzed. Intraclass correlation coefficients for all measurement parameters were in the range 0.889-0.997 (excellent), and all comparisons were statistically significant (p < 0.001). The range for femoral varus/valgus was 0.0-1.5°, with 96% of patients being within 0.5°. For femoral flexion/extension the range was 0.0-3.5° (92% within 2.5°). On the tibia, varus/valgus had a range of 0.0-1.0° (92% within 0.5°), and for slope the range was 0.0-3.5° (92% within 2.5°). The high degree of agreement indicated that intra-surgeon variation was minimal and that the technique is reliable.