Retention in care of infants diagnosed with HIV at birth: Beyond the diagnostic strategy.

Background: Birth HIV point-of-care (POC) tests curtail analytical testing issues and expedite diagnosis, potentially allowing for earlier mother-infant pair engagement and improved outcomes. Many children are lost post antiretroviral therapy (ART) initiation within the first 6 months of follow-up. Objectives: We compared 6-month retention in care, HIV viral load (VL) suppression and mortality among infants diagnosed with HIV at birth, using laboratory-based versus POC HIV PCR testing. Method: From 2018 to 2019, infants exposed to HIV underwent birth HIV PCR POC testing at Kalafong Provincial Tertiary Hospital in Tshwane District. Their outcomes were compared to a historical control born between 2014 and 2016, who exclusively underwent laboratory-based HIV PCR testing. Both groups received comparable HIV care following national guidelines. Results: Fifty-seven infants were studied (POC: 27; Control: 30). The POC turnaround time was significantly shorter (POC: 15.5 h [IQR: 4.3-24.7], Control: 68.3 h [IQR 46.0-93.9]; p = < 0.0001). Both populations had the same elapsed time from HIV diagnosis to ART initiation (median: 13 days, POC: IQR 8-21 days; Control: IQR 9-36 days). Six infants were never initiated (POC: 2 [7%]; Control: 4 [13%]). At 6 months, overall care retention was 72% (41/57), higher among the Control group (Control 23/30, 77%; POC: 18/27, 67%). HIV viral suppression at 6 months was higher among the POC group (POC: 14/18, 78%; Control: 9/19, 47%, p = 0.09). No deaths were reported. Conclusion: Poor care retention at 6 months post ART initiation is concerning. Initial mother-infant visits should be effectively utilised to assess and manage potential risk factors for loss of follow-up. Contribution: This study highlights the ongoing need to find workable solutions to improve retention in care, thereby ensuring the benefits of expedited HIV diagnosis and ART initiation.

Bridging Massive Acetabular Defects With the Triflange Cup: 10- to 28-Year Results.

BACKGROUND: Massive acetabular bone loss, encountered complex primary or revision total hip arthroplasty, remains a reconstructive challenge. The custom triflange cup reliably achieves both early fixation and longer-term stability. This study presents the 10-year minimum three-surgeon follow-up of acetabular defects managed with a custom triflange component. METHODS: All patients who underwent a custom triflange acetabular component implantation from January 1992 to December 2009 were identified. Demographics, implant data, outcomes, and reoperations were collected and analyzed. Bone defects in all cases were Paprosky type IIIA, IIIB, or IV. A total of 233 patients (241 hips) underwent implantation of a custom triflange during the study period. There were 81 patients (83 hips) who died prior to minimum follow-up and 84 patients (88 hips) had minimum follow-up of 10 years (mean 15.2; range, 10 to 28), or failure prior to 10 years. RESULTS: Complications requiring additional surgery occurred in 43 hips (49%). There were 10 revisions for failure (11.4%); four were due to recurrent infection, three for aseptic loosening, and one for recurrent infection with all revised to a new triflange. There was one patient who was resected to a Girdlestone for infection and one patient was revised for infection to a bipolar hemiprosthesis due to a healed discontinuity. CONCLUSION: To our knowledge, this study represents the largest cohort and longest follow-up in the current literature and demonstrates excellent survivorship and clinical results at an average of 15 years follow-up. The component was retained in 89% of cases.

Of bats and men: Immunomodulatory treatment options for COVID-19 guided by the immunopathology of SARS-CoV-2 infection.

In humans, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is highly infective, often causes severe acute and/or long-term illness, and elicits a high rate of mortality, even in countries with sophisticated medical systems. Detailed knowledge on the immune responses underpinning COVID-19 (coronavirus disease 2019), and on strategies SARS-CoV-2 uses to evade them, can provide pivotal guidance to researchers and clinicians developing and administering potentially life-saving immunomodulatory therapies. The need for such therapies in COVID-19 is unlikely to abate soon given the emergence of variants of concern that may pose new challenges for some vaccines and neutralizing antibodies. Here, we summarize current knowledge on COVID-19 immunopathogenesis in relation to three clinical disease stages and focus on immune evasion strategies used by pathogenic coronaviruses such as skewing type I, II, and III interferon responses and inhibiting detection via pattern recognition and antigen presentation. Insights gained from bats, which exhibit minimal disease in response to SARS-CoV-2 infection, offer an informative perspective and may guide future development of new therapies. We also discuss how knowledge of immunopathology may inform therapeutic decisions, for example, on selecting the most appropriate immunotherapeutic agents and timing their administration, to reduce morbidity and mortality of COVID-19.

Effects of intrauterine growth restriction on Ca2+-activated force and contractile protein expression in the mesenteric artery of 1-year-old Wistar-Kyoto rats.

Intrauterine growth restriction (IUGR) affects vascular reactivity in older rats, but at present the causative factors for this change are unknown. Therefore, we investigated downstream events associated with vascular reactivity, specifically, Ca2+-regulated force production and shifts in contractile protein content. The mesenteric artery from male and female 1-year-old Wistar-Kyoto rats was examined using two distinct experimental growth restriction models. Uterine ligation surgery restriction or a sham surgery was conducted at day 18 of pregnancy, whilst a food restriction diet (40% control diet) began on gestational day 15. Extracellular vascular reactivity was studied using intact mesenteric arteries, which were subsequently chemically permeabilized using 50 µM ß-escin to examine Ca2+-activated force. Peak contractile responses to a K+-induced depolarization and phenylephrine were significantly elevated due to an increase in maximum Ca2+-activated force in the male surgery restricted group. No changes in contractile forces were reported between female experimental groups. Sections of mesenteric artery were examined using western blotting, revealing IUGR increased the relative abundance of the voltage-gated Ca2+ channel, inositol-1,4,5-trisphosphate receptor and myosin light chain kinase, in both male growth restricted groups, whereas no changes were seen in females. These findings demonstrate for the first time in 1-year-old rats that changes in vascular reactivity due to IUGR are caused by a change in Ca2+-activated force and shifts in important contractile protein content. These changes affect the Wistar-Kyoto rat in a sex-specific and maternal insult-dependent manner.

The effect of intrauterine growth restriction on Ca2+ -activated force and contractile protein expression in the mesenteric artery of adult (6-month-old) male and female Wistar-Kyoto rats.

Intrauterine growth restriction (IUGR) is known to alter vascular smooth muscle reactivity, but it is currently unknown whether these changes are driven by downstream events that lead to force development, specifically, Ca2+ -regulated activation of the contractile apparatus or a shift in contractile protein content. This study investigated the effects of IUGR on Ca2+ -activated force production, contractile protein expression, and a potential phenotypic switch in the resistance mesenteric artery of both male and female Wistar-Kyoto (WKY) rats following two different growth restriction models. Pregnant female WKY rats were randomly assigned to either a control (C; N = 9) or food restriction diet (FR; 40% of control; N = 11) at gestational day-15 or underwent a bilateral uterine vessel ligation surgery restriction (SR; N = 10) or a sham surgery control model (SC; N = 12) on day-18 of gestation. At 6-months of age, vascular responsiveness of intact mesenteric arteries was studied, before chemically permeabilization using 50 µmol/L ß-escin to investigate Ca2+ -activated force. Peak responsiveness to a K+ -induced depolarization was decreased (P ≤ 0.05) due to a reduction in maximum Ca2+ -activated force (P ≤ 0.05) in both male growth restricted experimental groups. Vascular responsiveness was unchanged between female experimental groups. Segments of mesenteric artery were analyzed using Western blotting revealed IUGR reduced the relative abundance of important receptor and contractile proteins in male growth restricted rats (P ≤ 0.05), suggesting a potential phenotypic switch, whilst no changes were observed in females. Results from this study suggest that IUGR alters the mesenteric artery reactivity due to a decrease in maximum Ca2+ -activated force, and likely contributed to by a reduction in contractile protein and receptor/channel content in 6-month-old male rats, while female WKY rats appear to be protected.

Midterm Survivorship After Revision Total Hip Arthroplasty With a Custom Triflange Acetabular Component.

BACKGROUND: Custom triflange acetabular components are being increasingly used for the reconstruction of Paprosky type IIIB acetabular defects. However, midterm survivorship data are lacking. METHODS: We queried the prospective registries at 2 high-volume revision centers for patients who had undergone revision total hip arthroplasty using a custom triflange component between 2000 and 2011. We identified 73 patients with minimum 5-year follow-up. These patients' records were reviewed to determine incidence of revision or reoperation, clinical performance, and radiographic stability. The mean follow-up was 7.5 years (range 5-12 years). RESULTS: Fifteen of 73 triflange components (20.5%) were indicated for revision during the follow-up period, including 6 for instability (8%) and 8 for infection (11%). Twelve of 73 patients (16%) underwent reoperation for reasons other than failure of the triflange component. The median hip disability and osteoarthritis outcome score for joint replacement score at midterm follow-up was 85 (interquartile range 73-100). Only 1 of 73 implants was determined to be radiographically loose at midterm follow-up. CONCLUSION: Custom triflange reconstruction for severe acetabular deficiency is a viable option; however, complications are common and significant challenges remain for those that fail.

Usefulness of intraoperative radiographs in reducing errors of cup placement and leg length during total hip arthroplasty.

Traditional methods of component placement during total hip arthroplasty (THA) can lead to errors in cup abduction angle and leg length. Intraoperative radiographs were used to assess and correct errors during surgery in a consecutive series of 278 THAs performed by a single surgeon. After exclusions, 262 cases were available for cup abduction angle assessment and 224 for leg length discrepancy (LLD) assessment. Components were initially placed in a position determined as appropriate by the surgeon. Intraoperative radiographs were taken and appropriate corrections made. Postoperative radiographs were assessed at 6 weeks. Mean abduction angle on intraoperative radiographs was 39.6°±5.9° versus 38.6°±4.1° on postoperative radiographs. Thirty-eight cups were outside the target abduction range on intraoperative radiographs versus 4 on postoperative radiographs. Mean LLD was 3.7 mm ± 3.6 mm on intraoperative radiographs and 2.5 mm ± 2.7 mm on postoperative radiographs. Use of intraoperative radiographs is a valid, useful technique for minimizing errors in THA.

Are metal ion levels a useful trigger for surgical intervention?

The purpose of this study was to determine if cobalt and chromium ion levels can predict soft tissue damage at total hip revision. This study included 90 metal-on-metal total hip patients with preoperative cobalt and chromium ion levels. Tissue damage noted at revision surgery was graded on a 4-point scale. Sensitivity, specificity, and predictive values were calculated for various threshold values. Receiver operating characteristic analysis was conducted. Using 7 ppb as a threshold, cobalt and chromium ion levels had poor sensitivity and specificity (Co, 65% and 56%; Cr, 29% and 75%). Positive predictive values for cobalt and chromium were only 48% and 26% respectively. The area under the curve was 0.37 for cobalt and 0.44 for chromium. The length of time to revision significantly correlated with tissue damage (P = .001). Ion levels are unreliable predictors of periarticular soft tissue damage and should not be used in isolation as surgical intervention triggers.

Pelvic discontinuity treated with custom triflange component: a reliable option.

BACKGROUND: Pelvic discontinuity is an increasingly common complication of THA. Treatments of this complex situation are varied, including cup-cage constructs, acetabular allografts with plating, pelvic distraction technique, and custom triflange acetabular components. It is unclear whether any of these offer substantial advantages. QUESTIONS/PURPOSES: We therefore determined (1) revision and overall survival rates, (2) discontinuity healing rate, and (3) Harris hip score (HHS) after treatment of pelvic discontinuity with a custom triflange acetabular component and (4) the cost of this reconstructive operation compared to other constructs. METHODS: We retrospectively reviewed 57 patients with pelvic discontinuity treated with revision THA using a custom triflange acetabular component. We reviewed operative reports, radiographs, and clinical data for clinical and radiographic results. We also performed a cost comparison with utilization of other techniques. Minimum followup was 24 months (average, 65 months; range, 24-215 months). RESULTS: Fifty-six of 57 (98%) were free of revision for aseptic loosening at latest followup. Fifty-four (95%) were free of revision of the triflange component for any reason. Thirty-seven (65%) were free of revision for any reason. Twenty-eight (49%) were free of revision for any reason and free of any component migration and had a healed discontinuity. Forty-six (81%) had a stable triflange component with a healed pelvic discontinuity. Average HHS was 74.8. The costs of the custom triflange implants and a Trabecular Metal cup-cage construct were equivalent: $12,500 and $11,250, respectively. CONCLUSIONS: In this group of patients with osteolytic pelvic discontinuity, triflange implants provided predictable mid-term fixation at a cost equivalent to other treatment methods. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Trabecular metal endoprosthetic limb salvage reconstruction of the lower limb.

Currently, porous tantalum (trabecular metal) implants are widely accepted and frequently used for primary and revision hip and knee replacement surgery. This study examines the results of porous tantalum endoprostheses used to reconstruct large skeletal defects following resection of bone tumors. Seven custom tantalum implants were used to reconstruct 7 patients following resection for skeletal sarcomas in the femur and proximal tibia. Patient ages ranged from 13 to 71, with a mean of 34 years. Minimum patient follow-up was 6 years. The average Musculoskeletal Tumor Society functional evaluation score was 95 % of normal. There were no infections, hardware failures, or adverse events. One implant was revised 98 months post insertion because of fibrosis, loss of motion and loosening. In this small clinical series, the use of porous tantalum for limb salvage reconstruction is shown to be safe, to successfully provide osteointegration and soft tissue ingrowth, and to facilitate return of limb girdle muscle function.

Revision total knee arthroplasty: planning, management, and controversies.

The number of total knee arthroplasties (TKAs) performed annually in the United States is increasing exponentially. Even with modest annual revision rates, the number of patients requiring revision knee surgery will increase in a similar fashion. It is therefore important to have a systematic approach dealing with a patient presenting with a painful TKA. The treating physician must be able to recognize a variety of failure patterns and treat them accordingly. Surgical exploration in the absence of a definable cause is rarely successful and should be avoided. The ability to plan and execute a complex revision TKA is a challenging and rewarding aspect of adult reconstructive surgery. Commonly encountered mechanisms of failure are identified and a stepwise approach to the surgical management of these conditions is presented.

Revision total hip arthroplasty for pelvic discontinuity.

BACKGROUND: Revision of a failed total hip arthroplasty with massive acetabular bone loss and pelvic discontinuity is a reconstructive challenge. This report presents the mid-term to long-term results of revision total hip arthroplasty with a custom-made porous-coated triflange acetabular prosthesis in a consecutive series of patients with pelvic discontinuity. METHODS: Twenty-eight consecutive patients (thirty hips) with a failed total hip arthroplasty and pelvic discontinuity underwent revision total hip arthroplasty. The prosthesis was custom-manufactured on the basis of a three-dimensional model of the hemipelvis created with computed tomography. Initial stability of the implant was provided with screw fixation. Two patients did not return for follow-up after three months, and eight died and were followed for less than seven years, leaving twenty hips in eighteen patients followed for a mean of ten years. Harris hip scores and sequential radiographs were used to evaluate the clinical and radiographic results. RESULTS: Definite healing of the pelvic discontinuity was indicated by the presence of bridging callus in eighteen of the twenty hips. There were no broken screws and no cases of implant migration, even when the discontinuity persisted. Small nonprogressive radiolucent lines were observed in six hips. Complications included one partial sciatic nerve palsy that resolved completely and one case of loose ischial screws in a radiographically stable implant in the same patient. Five patients had one or more dislocations postoperatively. The mean Harris hip score improved from 41 points preoperatively to 80 points at the time of the latest follow-up. Eleven of the eighteen patients required ambulatory aids postoperatively. No component was revised. CONCLUSIONS: Performance of a revision total hip arthroplasty with a custom triflange acetabular prosthesis to treat massive acetabular bone loss and pelvic discontinuity can provide a durable solution with good clinical results. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

Predictors of paralysis in the rheumatoid cervical spine in patients undergoing total joint arthroplasty.

BACKGROUND: Rheumatoid arthritis is sometimes associated with radiographic evidence of instability of the cervical spine, most commonly an abnormal subluxation between vertebrae. When this instability compromises the space that is available for the spinal cord, it may be predictive of paralysis. However, the prevalence of radiographic signs of instability that are predictive of paralysis among patients with nonspinal orthopaedic manifestations of rheumatoid arthritis is unknown. METHODS: Radiographs of the cervical spine of patients with rheumatoid arthritis who had undergone total joint arthroplasty over a five-year period were retrospectively reviewed. The radiographs were evaluated for predictors of paralysis (a posterior atlantodental interval of <14 mm or a subaxial space available for the cord measuring <14 mm) and were compared with traditional parameters of instability (an anterior atlantodental interval of >3 mm or subaxial subluxation of >3 mm). RESULTS: Forty-nine of the sixty-five patients who were identified had flexion and extension lateral radiographs available for review. Only one of these patients had a posterior atlantodental interval of <14 mm, and only three had a space available for the cord that measured <14 mm at one level or more. In comparison, twenty patients had radiographic evidence of instability on the basis of traditional parameters. CONCLUSIONS: Although nearly one-half of the patients in the present study had radiographic evidence of cervical instability on the basis of traditional measurements, only four patients (8%) had a radiographic finding that was predictive of paralysis. Thus, while radiographic evidence of cervical instability was not infrequent in this population of patients who underwent total joint arthroplasty for rheumatoid arthritis, radiographic predictors of paralysis were much less common.

Beyond cementless hemispherical sockets.

One of the major goals of acetabular revision is achieving stability. To achieve intimate contact between the implant and host bone, which is critical for stability since bone ingrowth requires the absence of micromotion, the implant must match the defect or be able to bridge the defect. Hemispherical sockets can achieve long-term implant fixation in acetabular defects that are not extensive, whereas structural allografts are associated with long-term failure and reliance on them dooms the implant to failure. Increasing bone loss requires the use of implants that may not be hemispherical, such as the Oblong Cup, or devices that bridge the defect such as an antiprotrusio cage or Triflange Cup.

Clinical applications of Trabecular Metal.

Trabecular Metal (porous tantalum) offers a viable solution to several challenges in orthopedic reconstructive surgery, including monoblock acetabular cups, avascular necrosis intervention devices, and total hip reconstruction in situations of massive femoral bone loss. Porous tantalum approaches the ideal biomaterial: it is porous, strong, flexible, and biocompatible. For use in components for total hip arthroplasty, porous tantalum provides a substitute for lost bone, immediate bone loading, bone ingrowth, and soft-tissue attachment. It can be machine-shaped into custom designs in situations of massive bone loss.