Concurrent advanced HIV disease and viral load suppression in a high-burden setting: Findings from the 2015-6 ZIMPHIA survey.

BACKGROUND: As Zimbabwe approaches epidemic control of HIV, programs now prioritize viral load over CD4 monitoring, making it difficult to identify persons living with HIV (PLHIV) suffering from advanced disease (AD). We present an analysis of cross-sectional ZIMPHIA data, highlighting PLHIV with AD and concurrent viral load suppression (VLS). METHODS: ZIMPHIA collected blood specimens for HIV testing from 22,501 consenting adults (ages 15 years and older); 3,466 PLHIV had CD4 and VL results. Household HIV testing used the national serial algorithm, and those testing positive then received point-of-care CD4 enumeration with subsequent VL testing. We used logistic regression analysis to explore factors associated with concurrent AD and VLS (<1000 copies/mL). All analyses were weighted to account for complex survey design. RESULTS: Of the 3,466 PLHIV in the survey with CD4 and VL results, 17% were found to have AD (CD4<200cells/mm3). Of all AD patients, 30% had VLS. Concurrent AD and VLS was associated with male sex (aOR 2.45 95%CI 1.61-3.72), older age (35-49 years [aOR 2.46 95%CI 1.03-5.91] and 50+ years [aOR 4.82 95%CI 2.02-11.46] vs 15-24 years), and ART duration (<6 months [aOR 0.46 95%CI 0.29-0.76] and 6-24 months [aOR 2.07 95%CI 1.35-3.17] vs more than 2 years). The relationship between sex and AD is driven by age with significant associations among men aged 25-34, (aOR 3.37 95%CI 1.35-8.41), 35-49 (aOR 5.13 95%CI 2.16-12.18), and 50+ (aOR 12.56 95%CI 4.82-32.72) versus men aged 15-24. CONCLUSIONS: The percentage of PLHIV with AD and VLS illustrates the conundrum of decreased support for CD4 monitoring, as these patients may not receive appropriate clinical services for advanced HIV disease. In high-prevalence settings such as Zimbabwe, CD4 monitoring support warrants further consideration to differentiate care appropriately for the most vulnerable PLHIV. Males may need to be prioritized, given their over-representation in this sub-population.

Immune function assay (immunknow) drop over first 6 months after renal transplant: a predictor of opportunistic viral infections?

BACKGROUND: The Immuknow assay (IKA; Cylex) is a T-cell immune function assay that evaluates immunoreactivity in immunocompromised patients. The aim of this study was to analyze IKA values in a cohort of kidney transplantation (KT) recipients to investigate correlations between single-time point low IKA values and their trend over time with cytomegalovirus (CMV) or BK virus (BKV) reactivation. METHODS: A total of 118 adult patients receiving deceased-donor KT were enrolled (55.6±11.9 years old; 79 [66.9%] male). IKA CMV and BKV viremia determinations and were performed at months 1, 3, and 6 after surgery. RESULTS: Overall, 272 IKA determinations were performed: IKA values significantly decreased from month 1 (422±184 ng/mL) to month 3 (330±159 ng/mL; P<.001) and from month 3 to month 6 (300±128 ng/mL; P=.030). IKA values did not correlate with renal function or viral reactivation at any time. However, patients with either CMV or BKV viremia had a trend to higher IKA values at month 1 and lower IKA values at month 6, even if the difference did not reach a statistical significance (P=.115). CONCLUSIONS: Our study suggests that presence of low immunologic reactivity (IKA<225 ng/mL) is not associated with an increased risk of CMV and BKV reactivation over the 1st 6 months after KT. However, a trend to a more pronounced drop in IKA values over time was observed in patients with viral reactivation. These preliminary results suggests that drop in IKA values within the 1st post-KT months, unlike single-time point immune function assay, may predict the risk of opportunistic viral infections.

A randomized trial comparing heater probe plus thrombin with heater probe plus placebo for bleeding peptic ulcer.

BACKGROUND & AIMS: This multicenter, double-blind, controlled trial compared the efficacy of combined endoscopic hemostatic treatment using the heater probe plus thrombin injection with that of the heater probe plus placebo injection as treatment for peptic ulcers with active bleeding or nonbleeding visible vessels. Efficacy was defined in terms of primary hemostasis, prevention of rebleeding, and need for urgent surgery. METHODS: Two hundred forty-seven patients presenting with major peptic ulcer bleeding were randomized to heater probe plus thrombin or to heater probe plus placebo. The groups were well matched for all risk categories including age, endoscopic stigmata, shock, and severity of comorbid diseases. Endoscopic therapy was applied using the heater probe followed by injection of thrombin or placebo. RESULTS: Successful primary hemostasis was achieved in 97% of patients. Rebleeding developed in 19 (15%) of thrombin plus heater probe patients and 17 (15%) of placebo plus heater probe patients. Emergency surgery was necessary in 16 and 13 patients, respectively. Eight patients in the thrombin group had adverse events compared with 4 in the placebo group. Eight (6%) of thrombin plus heater probe patients and 14 (12%) of placebo plus heater probe patients died (P = 0.21). CONCLUSIONS: The combination of thrombin and the heater probe does not confer an additional benefit over heater probe and placebo as endoscopic treatment for bleeding peptic ulcer. Our trial does not support the use of this combination of hemostatic therapy.

Damage type and strain mode associations in human compact bone bending fatigue.

When compact bone is subjected to fatigue loading, it develops matrix microdamage, which reduces the tissue's ability to resist fracture. The relative influence of different strain modes on damage and strength in compact bone has not been characterized, to our knowledge. In this study, the nonuniform strain field produced by four-point bending was used to introduce fatigue damage into tibial bending beam specimens from men 40-49 years old. The specimens were then bulk-stained with basic fuchsin to mark damage surfaces and were examined histologically and with confocal microscopy to describe damage morphologies and position relative to tension and compression-strained regions of the specimen. Histomorphometric methods were used to quantify the amounts of different types of bone microdamage. Three major types were observed. In regions subjected to tensile strains, the bone had focal regions of diffusely increased basic fuchsin staining (i.e., diffuse microdamage). Confocal microscopy of these regions showed them to be composed of extensive networks of fine, ultrastructural-level cracks. In compressive strain regions, the tissue developed linear microcracks in interstitial areas similar to those originally described by Frost. Fine, tearing-type (wispy-appearing) cracks were observed near and in the plane of the neutral axis. The paths of these fine cracks were not influenced by microstructural boundaries. Other minor damage morphologies (sector-stained osteons, delamination of regions of lamellae, and intraosteonal cracking) were observed, but their distribution was unrelated to local strain field. Thus. in fatigue of human compact bone, the principal mechanisms of matrix failure (i.e., linear microcrack, diffuse damage foci, and tearing-type damage) are strongly dependent on local strain type.

A curriculum for the ideal orthopaedic residency. Academic Orthopaedic Society.

The Academic Orthopaedic Society met in April 1994 to discuss manpower issues in orthopaedics. The members developed an approach using the Delphi system to define and obtain consensus on the characteristics of the ideal residency. Six categories of educational attributes were included: General; Clinical Management; Skills and Technical Aspects; Rehabilitation; Basic Science and Research; and Educational Environment. The following year a questionnaire was sent to more than 125 programs in an attempt to have residents and staff anonymously self score their residencies according to the standards defined by the Delphi panels. The results obtained from the 745 responders from 73 programs validate effectively the characteristics of the ideal program and also show the variation among the programs.

Anterior knee pain caused by overactivity: a long term prospective followup.

In a prospective study to determine the natural history of anterior knee pain caused by overactivity, 60 (15%) of 390 elite Israeli infantry recruits were found to have anterior pain in 77 knees during 14 weeks of basic training. At 6 years' followup, 3 years after returning to civilian life, half of the knees originally with anterior knee pain were still symptomatic, but in only 8% of the originally symptomatic knees was the pain severe, hindering physical activity. The long term prognosis of anterior knee pain caused by overactivity is much better than that reported previously for anterior knee pain in adolescents, but in a small percentage of cases the pain persists at a level that may prevent participation in exertional activities.

MRI protocol for critically ill patients.

BACKGROUND Ventilators compatible with magnetic resonance imaging machines are not universally available. However, the lack of such equipment should not preclude magnetic resonance imaging. We have developed a method by which a critically ill patient requiring mechanical ventilation can safely undergo such imaging without compatible equipment. METHOD By using extended ventilator tubing and calculating volume lost due to tubing compliance, safe and reliable mechanical ventilation can be achieved from a distance without impairing scan quality. RESULTS We devised a method to calculate volume lost due to mechanical compliance of the tubing with ventilator circuits employing 20, 30, and 50 feet of tubing. We added the estimated loss of volume to the set tidal volume of 700 mL to give a delivered volume of 700 mL. Twenty breaths were evaluated for each length of tubing. The evaluation of the 20- and 30-foot lengths of tubing demonstrated 10- and 52-mL discrepancies, respectively, between predicted and measured volumes. The 50-foot length showed a 121-mL discrepancy between predicted and measured volumes. CONCLUSIONS Our method appears to be clinically accurate for predicting volume lost due to tubing compliance for lengths of ventilator tubing less than or equal to 30 feet. We have found this technique to be a safe and effective way to ensure patient safety and scan quality in patients requiring mechanical ventilation during magnetic resonance imaging.

Unexpected phenotypes and predominant TCR V gene usage in random selected subjects.

The presence of a subset of T lymphocytes with an irregular phenotype has been identified in the peripheral blood of 22 subjects, selected among more than 5000 individuals evaluated for peripheral blood lymphocyte subset distribution as part of a routine procedure. By Southern Blot Analysis 13 out of 14 of the analysed samples presented additional non-germline bands, indicative of monoclonal or oligoclonal T cell expansions. Moreover, the cytometric analysis showed that 7 out of 19 analysed samples were restricted for a subfamily of the TCR variable regions. Thus, lymphocyte subsets with phenotypic irregularities could represent the clonally driven expansion of otherwise normally subpopulations, which may be present in peripheral blood below the limit of detection of routine phenotypic analyses. Such clonal populations could exert a regulatory activity either on the pathogenetic mechanisms of the disease or in maintaining homeostasis in healthy people.

Treatment of overuse patellofemoral pain. Prospective randomized controlled clinical trial in a military setting.

The efficacy of treatment of overuse patellofemoral pain with an elastic knee sleeve with a silicone patellar ring was compared with a simple elastic sleeve and with no treatment in a prospective study of 395 army recruits. During 14 weeks of basic training, 84 knees were diagnosed as having overuse patellofemoral pain. Recruits treated with a simple elastic knee sleeve had a statistically significant better comfort score and more had their pain resolved by the end of training than those treated with elastic knee sleeves with a silicone patellar ring. The mean pain score at the end of training decreased more among recruits who were treated with a simple elastic knee sleeve than among recruits who received no treatment, but this difference was not significant. Among the treatment options tried, the simple elastic knee sleeve was no more effective than no treatment at all, but it was more effective than the more elaborate patellar brace.

Long-term follow-up study on the Maquet procedure with special reference to the causes of failure.

Thirty-nine patients with symptomatic osteoarthrosis (OA) of the patellofemoral joint were treated with 42 anterior tibial tubercle elevations, also known as the Maquet procedure. The patients all had symptomatic OA of the patellofemoral joint that fell into one of three categories: old patellar fracture, chronic patellar subluxation, or postpatellectomy pain. In the latter group, the OA was manifested by erosions of trochlear articular cartilage from the articulating quadriceps tendon-patellar ligament suture line. All 39 patients had a 1.5-2.5-cm tibial tubercle elevation with medial displacement, as necessary, to centralize their patellofemoral mechanisms. Follow-up period averaged 6.1 years. Seventy-nine percent (33 of 42 procedures) had good to excellent results. There was a major complication rate of 7%. Six of the nine failures were attributable to social/psychiatric reasons. Previously unrecognized tibiofemoral OA was the reason for poor results in two of the other failures, and one failure was unexplained. Patients with long-standing symptoms caused by patellofemoral OA should preoperatively be psychologically evaluated and diagnostically arthroscoped before the Maquet procedure is carried out.

The Maquet procedure: effect of tibial shingle length on patellofemoral pressures.

The Maquet procedure--elevation of the anterior tibial tubercle--has been recommended for treatment of symptomatic osteoarthrosis of the patellofemoral joint. Although the operation was first described 30 years ago, it remains controversial, both on a clinical and on a biomechanical basis. In addition, deterioration of the long-term results has been suggested. One of the variables that has been ignored in both clinical and biomechanical studies has been tibial shingle length. In order to judge its effect, we examined contact pressures and areas in 15 cadaver knees with 7 and 20 cm tibial shingle lengths. We found significant patellofemoral pressure diminution only with 2 cm elevations. The short anterior tibial shingle with 2 cm of elevation tipped the patella on its superior pole, with a significant change in angle between the patella and the shingle. We suggest that this creates a potentially less than desirable biomechanical circumstance and believe it may explain the discrepancies among previously published reports.

Cytofluorimetric identification of two populations of double positive (CD4+,CD8+) T lymphocytes in human peripheral blood.

Two different subsets of CD4+,CD8+ T lymphocytes have been identified in peripheral blood collected from normal subjects and from patients with different diseases. The subpopulations differed in the degree of CD4 and CD8 antigen expression. Hence, it was possible to distinguish by cytofluorimetric analysis cells with a low (dim) or with a high (bright) fluorescence intensity after the staining with anti-CD4 or anti-CD8 mAbs. CD4+dim,CD8+bright lymphocytes were found in patients with EBV-infectious mononucleosis and were present for less than a month. CD4+bright,CD8+dim T cells were observed in neoplastic patients as well as in healthy subjects and were continuously present in similar percentages over a long period of time (at the moment, about 3 years). Both the subpopulations expressed CD2, CD3, CD5 antigens and had an alpha beta-TCR, but did not express CD1a or CD7. Only CD4+dim,CD8+bright cells expressed HLA-DR antigen and the activation marker CD38, while only CD4+bright,CD8+dim lymphocytes expressed CD56 and CD57 molecules. The hypothesis may be put forward that these two subsets represent an effort of the immune system to cope with different requirements, i.e., of viral or neoplastic origin, while it is not clear the meaning of these cells in healthy subjects.

The influence of basal cartilage calcification on dynamic juxtaarticular stress transmission.

Dynamic finite element analysis is used to elucidate the manner in which juxtaarticular stress distributions depend on the transitional mechanical properties of the calcified cartilage layer. A finite element model is used to study how these stresses change in response to the thinning of the articular cartilage layer associated with tidemark advancement. The finite element results indicate that shear stress levels within the deepest layer of articular cartilage are increased when tidemark advancement with concomitant cartilage-thinning and calcified cartilage/subchondral plate thickening is modeled. The cartilage-thinning associated with tidemark advancement, observed both clinically and experimentally, may be an explanation for what has previously been considered wear-related thinning.

Mechanical determinants of osteoarthrosis.

The joint is an organ and functions as a mechanical bearing created of biological materials. In the joint, as in all connective tissues, there is a relationship between mechanical factors and tissue behavior. Therefore, it is not surprising that joint health and osteoarthrosis are reflections of both mechanical and biological factors. Osteoarthrosis is not a disease, but organ failure caused initially by mechanical factors. The biological changes follow. There is no habitual pathophysiological cascade. Osteoarthrosis is best thought of not as a common final pathway, but as a common end stage. The hypotheses that in osteoarthrosis substructural disorganization of the matrix proceeds chondrocytic enzyme production, that impulsive loading is an essential factor in the progressive cartilage destruction, and that tidemark advancement and horizontal cartilage splitting are the primary mechanisms in progressive cartilage loss are discussed.