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1.
Glob Public Health ; 19(1): 2290117, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38118118

ABSTRACT

At the beginning of the COVID-19 pandemic, the Kenya Ministry of Health instituted movement cessation measures and limits on face-to-face meetings. We explore the ways in which female sex workers (FSWs) in Nairobi were affected by the COVID-19 control measures and the ways they coped with the hardships. Forty-seven women were randomly sampled from the Maisha Fiti study, a longitudinal study of 1003 FSWs accessing sexual reproductive health services in Nairobi for an in-depth qualitative interview 4-5 months into the pandemic. We sought to understand the effects of COVID-19 on their lives. Data were transcribed, translated, and coded inductively. The COVID-19 measures disenfranchised FSWs reducing access to healthcare, decreasing income and increasing sexual, physical, and financial abuse by clients and law enforcement. Due to the customer-facing nature of their work, sex workers were hit hard by the COVID-19 restrictions. FSWs experienced poor mental health and strained interpersonal relationships. To cope they skipped meals, reduced alcohol use and smoking, started small businesses to supplement sex work or relocated to their rural homes. Interventions that ensure continuity of access to health services, prevent exploitation, and ensure the social and economic protection of FSWs during times of economic strain are required.


Subject(s)
COVID-19 , HIV Infections , Sex Workers , Female , Humans , Sex Workers/psychology , Pandemics , Kenya/epidemiology , Longitudinal Studies , COVID-19/epidemiology , HIV Infections/prevention & control
2.
Cureus ; 15(9): e44533, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37790014

ABSTRACT

Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of metastatic cancer affecting the pia and arachnoid mater. It has been postulated that recent improvements in cancer patient survival time have increased the frequency of LC and other rare metastatic conditions that patients previously would not have lived long enough to experience. LC carries a universally poor prognosis with a mean survival of between two to four months if treated; however, the recent increase in incidence has allowed for further research into the condition and potential treatments. Options for administering chemotherapy have been limited in the past, but recent developments in surgical chemotherapeutic ports have allowed for intrathecal delivery of drugs like methotrexate without systemic exposure. In fact, innovative delivery systems undergoing clinical trials can deliver these drugs in a metronomic fashion to limit the leukoencephalopathy complications of methotrexate. Primary breast cancer is the most common source of metastatic leptomeningeal lesions, and such a lesion was observed by the authors in the cadaver of a 70-year-old Caucasian female with unspecified breast cancer in a medical school anatomic laboratory. The cause of death was listed as "complication of malignant neoplasm of unspecified site of unspecified female breast." Through this case report, we seek to develop our understanding of this rare metastatic phenomenon and highlight the importance of student cadaveric dissection.

3.
Cureus ; 15(4): e37556, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37193471

ABSTRACT

The advent of immune checkpoint inhibitors (ICIs) in the field of oncology has improved the outcome response rate for a variety of neoplastic pathologies with improved cellular specificity that lacks the traditional adverse effects associated with chemotherapy. However, ICIs are not without adverse associations, and a growing concern for modern clinicians is the balancing of interests that most occur to minimize these adverse effects while also improving patients' conditions from an oncologic perspective. This case presents a 69-year-old man who developed multiple episodes of significant pericardial effusion while receiving infusions of pembrolizumab for stage III-A adenocarcinoma for which he underwent a pericardiostomy procedure. Given the positive response of this immunotherapy on disease progression, the decision was made to continue the administration of pembrolizumab following the pericardiostomy with the plan of using serial echocardiography studies to monitor for the presence of clinically significant pericardial effusion in the future. In this way, the patient will still be able to receive optimal treatment for his advanced cancer while preserving adequate cardiac function.

4.
Adv Mater ; 35(20): e2210068, 2023 May.
Article in English | MEDLINE | ID: mdl-36852617

ABSTRACT

Multienergy X-ray detection is critical to effectively differentiate materials in a variety of diagnostic radiology and nondestructive testing applications. Silicon and selenium X-ray detectors are the most common for multienergy detection; however, these present poor energy discrimination across the broad X-ray spectrum and exhibit limited spatial resolution due to the high thicknesses required for radiation attenuation. Here, an X-ray detector based on solution-processed thin-film metal halide perovskite that overcomes these challenges is introduced. By harnessing an optimized n-i-p diode configuration, operation is achieved across a broad range of soft and hard X-ray energies stemming from 0.1 to 10's of keV. Through detailed experimental and simulation work, it is shown that optimized Cs0.1 FA0.9 PbI3 perovskites effectively attenuate soft and hard X-rays, while also possessing excellent electrical properties to result in X-ray detectors with high sensitivity factors that exceed 5 × 103 µ C G y Vac - 1 cm - 2 $\mu {\rm{C}}\;{{\bf Gy}}_{{\rm{Vac}}}^{ - 1}\;{\rm{c}}{{\rm{m}}^{ - 2}}$ and 6 × 104 µC Gy-1 cm-2 within soft and hard X-ray regimes, respectively. Harnessing the solution-processable nature of the perovskites, roll-to-roll printable X-ray detectors on flexible substrates are also demonstrated.

5.
Sci Rep ; 12(1): 18469, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36323686

ABSTRACT

The ill-posed problem of phase retrieval in optics, using one or more intensity measurements, has a multitude of applications using electromagnetic or matter waves. Many phase retrieval algorithms are computed on pixel arrays using discrete Fourier transforms due to their high computational efficiency. However, the mathematics underpinning these algorithms is typically formulated using continuous mathematics, which can result in a loss of spatial resolution in the reconstructed images. Herein we investigate how phase retrieval algorithms for propagation-based phase-contrast X-ray imaging can be rederived using discrete mathematics and result in more precise retrieval for single- and multi-material objects and for spectral image decomposition. We validate this theory through experimental measurements of spatial resolution using computed tomography (CT) reconstructions of plastic phantoms and biological tissues, using detectors with a range of imaging system point spread functions (PSFs). We demonstrate that if the PSF substantially suppresses high spatial frequencies, the potential improvement from utilising the discrete derivation is limited. However, with detectors characterised by a single pixel PSF (e.g. direct, photon-counting X-ray detectors), a significant improvement in spatial resolution can be obtained, demonstrated here at up to 17%.


Subject(s)
Algorithms , Tomography, X-Ray Computed , Phantoms, Imaging , Tomography, X-Ray Computed/methods , Photons , Mathematics
6.
BMC Public Health ; 22(1): 2158, 2022 11 24.
Article in English | MEDLINE | ID: mdl-36418973

ABSTRACT

BACKGROUND: Female sex workers (FSWs) in Kenya are at an increased risk of violence, poverty, police arrest, and problematic alcohol and other substance use, all of which are linked to poor mental health and suicidal ideation. Despite the psychological stressors experienced by FSWs, there is no published qualitative methods research investigating their mental health experiences in Kenya. In this paper, we draw on data from in-depth interviews to examine FSWs' lifetime mental health experiences and perceived risk factors. METHODS: We used baseline in-depth interviews of the Maisha Fiti longitudinal study of FSWs in Nairobi. We randomly selected 40 FSWs from 1003 FSWs who attended a baseline behavioural-biological interview as part of the Maisha Fiti study. The interview guide was semi-structured, and participants were asked to detail their life stories, including narrating specific events such as entry into sex work, experiences of violence, mental health experiences, and use of alcohol and other substances. Interviews were recorded in Kiswahili/ English and transcribed in English. Data were coded and thematically analysed in Nvivo (v.12). RESULTS: Results indicated that the majority of participants understood 'mental health' as 'insanity', 'stress', 'depression', and 'suicide'; nevertheless, a number described mental health symptomatically, while a few believed that mental health problems were caused by witchcraft. Interestingly, poverty, low levels of education, poor job opportunities, a lack of family support, harmful gender norms, intimate partner violence and subsequent relationship breakdowns, and family bereavement all contributed to poor mental health and subsequent entry into sex work. In addition, the consequences of sex work such as sexual risks, and ongoing violence from police and clients, further exacerbated poor mental health. CONCLUSIONS: There is a need for both micro- and macro interventions to address poverty and violence against FSWs in Kenya, thereby reducing mental health problems. Addressing violence against women and girls may also reduce entry into sex work. Improving mental health literacy and providing mental health intervention services for 'at-risk' populations such as FSWs should enhance coping strategies and help-seeking efficacy.


Subject(s)
Sex Workers , Female , Humans , Sex Workers/psychology , Longitudinal Studies , Kenya/epidemiology , Sex Work/psychology , Violence
7.
Front Pediatr ; 10: 990923, 2022.
Article in English | MEDLINE | ID: mdl-36245717

ABSTRACT

Background: Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration. Methods: Deceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0-50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges. Results: All LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r 2 = 0.71). Conclusion: LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.

8.
IEEE Trans Med Imaging ; 41(8): 2170-2179, 2022 08.
Article in English | MEDLINE | ID: mdl-35259098

ABSTRACT

In X-ray imaging, photons are transmitted through and absorbed by the target object, but are also scattered in significant quantities. Previous attempts to use scattered X-ray photons for imaging applications used pencil or fan beam illumination. Here we present 3D X-ray Scatter Tomography using full-field illumination for small-animal imaging. Synchrotron imaging experiments were performed on a phantom and the chest of a juvenile rat. Transmitted and scattered photons were simultaneously imaged with separate cameras; a scientific camera directly downstream of the sample stage, and a pixelated detector with a pinhole imaging system placed at 45° to the beam axis. We obtained scatter tomogram feature fidelity sufficient for segmentation of the lungs and major airways in the rat. The image contrast in the scatter tomogram slices approached that of transmission imaging, indicating robustness to the amount of multiple scattering present in our case. This opens the possibility of augmenting full-field 2D imaging systems with additional scatter detectors to obtain complementary modes or to improve the fidelity of existing images without additional dose, potentially leading to single-shot or reduced-angle tomography or overall dose reduction for live animal studies.


Subject(s)
Photons , Tomography, X-Ray Computed , Animals , Phantoms, Imaging , Rats , Scattering, Radiation , Tomography, X-Ray Computed/methods , X-Rays
9.
J Med Imaging (Bellingham) ; 9(3): 031506, 2022 May.
Article in English | MEDLINE | ID: mdl-35310451

ABSTRACT

Purpose: Propagation-based x-ray imaging (PBI) is a phase-contrast technique that is employed in high-resolution imaging by introducing some distance between sample and detector. PBI causes characteristic intensity fringes that have to be processed with appropriate phase-retrieval algorithms, which has historically been a difficult task for objects composed of several different materials. Spectral x-ray imaging has been introduced to PBI to overcome this issue and to potentially utilize the spectral nature of the data for material-specific imaging. We aim to explore the potential of spectral PBI in three-dimensional computed tomography (CT) imaging in this work. Approach: We demonstrate phase-retrieval for experimental high-resolution spectral propagation-based CT data of a simple two-component sample, as well as a multimaterial capacitor test sample. Phase-retrieval was performed using an algorithm based on the Alvarez-Macovski model. Virtual monochromatic (VMI) and effective atomic number images were calculated after phase-retrieval. Results: Phase-retrieval results from the spectral data set show a distinct gray-level for each material with no residual phase-contrast fringes. Several representations of the phase-retrieved data are provided. The VMI is used to display an attenuation-equivalent image at a chosen display energy of 80 keV, to provide good separation of materials with minimal noise. The effective atomic number image shows the material composition of the sample. Conclusions: Spectral photon-counting detector technology has already been shown to be compatible with spectral PBI, and there is a foreseeable need for robust phase-retrieval in high-resolution, spectral x-ray CT in the future. Our results demonstrate the feasibility of phase-retrieval for spectral PBI CT.

11.
IEEE Trans Med Imaging ; 39(12): 3891-3899, 2020 12.
Article in English | MEDLINE | ID: mdl-32746132

ABSTRACT

Material decomposition in X-ray imaging uses the energy-dependence of attenuation to digitally decompose an object into specific constituent materials, generally at the cost of enhanced image noise. Propagation-based X-ray phase-contrast imaging is a developing technique that can be used to reduce image noise, in particular from weakly attenuating objects. In this paper, we combine spectral phase-contrast imaging with material decomposition to both better visualize weakly attenuating features and separate them from overlying objects in radiography. We derive an algorithm that performs both tasks simultaneously and verify it against numerical simulations and experimental measurements of ideal two-component samples composed of pure aluminum and poly(methyl methacrylate). Additionally, we showcase first imaging results of a rabbit kitten's lung. The attenuation signal of a thorax, in particular, is dominated by the strongly attenuating bones of the ribcage. Combined with the weak soft tissue signal, this makes it difficult to visualize the fine anatomical structures across the whole lung. In all cases, clean material decomposition was achieved, without residual phase-contrast effects, from which we generate an un-obstructed image of the lung, free of bones. Spectral propagation-based phase-contrast imaging has the potential to be a valuable tool, not only in future lung research, but also in other systems for which phase-contrast imaging in combination with material decomposition proves to be advantageous.


Subject(s)
Algorithms , Image Processing, Computer-Assisted , Animals , Phantoms, Imaging , Rabbits , Radiography , X-Rays
12.
Biotechnol Prog ; 33(4): 854-866, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28480535

ABSTRACT

This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool that integrated process economics, discrete-event simulation, environmental impact analysis, operational risk analysis, and multiattribute decision-making. The case study focused on comparing whole bioprocesses that used either batch, continuous or a hybrid combination of batch and continuous technologies for cell culture, capture chromatography, and polishing chromatography steps. The cost of goods per gram (COG/g), E-factor, and operational risk scores of each strategy were established across a matrix of scenarios with differing combinations of clinical development phase and company portfolio size. The tool outputs predict that the optimal strategy for early phase production and small/medium-sized companies is the integrated continuous strategy (alternating tangential flow filtration (ATF) perfusion, continuous capture, continuous polishing). However, the top ranking strategy changes for commercial production and companies with large portfolios to the hybrid strategy with fed-batch culture, continuous capture and batch polishing from a COG/g perspective. The multiattribute decision-making analysis highlighted that if the operational feasibility was considered more important than the economic benefits, the hybrid strategy would be preferred for all company scales. Further considerations outside the scope of this work include the process development costs required to adopt continuous processing. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:854-866, 2017.


Subject(s)
Antibodies, Monoclonal/economics , Biotechnology , Decision Making , Manufacturing Industry/economics , Antibodies, Monoclonal/biosynthesis , Batch Cell Culture Techniques/economics , Chromatography/economics , Environment
13.
Proc Natl Acad Sci U S A ; 110(39): 15585-90, 2013 Sep 24.
Article in English | MEDLINE | ID: mdl-24019475

ABSTRACT

A powerful strategy to obtain complex supramolecular materials is the bottom-up construction of noncovalently bound materials by hierarchical self-assembly. This assembly process involves stepwise, uniform increases to the architectural complexity of a substrate, starting from discrete precursors and growing in dimensionality through controlled reactivity to a final product. Herein, two orthogonal processes are exploited: coordination-driven self-assembly and hydrogen bonding. The former relies on the predictable formation of metal-ligand bonds wherein the directionalities of the rigid precursors used determines the structural outcome. The latter uses 2-ureido-4-pyrimidinone interfaces that are structurally robust by virtue of the quadruple hydrogen bonding that can occur between subunits. By combining these two processes into a single system, it is possible to generate hierarchical materials that preserve the attractive tunability associated with discrete supramolecular coordination complexes. For instance, the synthesis of a one-dimensional chain comprising linked metalla-rhomboids is readily adapted to a 2D cross-linked hexagonal network by simply selecting a different metal acceptor precursor as an assembly component. The specific interactions between subunits, in this case platinum(II)-pyridyl bonds and the quadruple H-bonding of ureidopyrimidinone, are unchanged, establishing a unique strategy to obtain supramolecular polymers with marked topological differences with minimal synthetic redesign. In addition, the structural rigidity imposed by the inclusion of the platinum metallacycles serves to minimize the formation of cyclic oligomers, increasing the efficacy of formation and improving the properties of the resultant materials. Furthermore, this study taps the potential of organoplatinum(II) metallacycles in materials science.

14.
J Homosex ; 60(5): 773-95, 2013.
Article in English | MEDLINE | ID: mdl-23593958

ABSTRACT

Interviews from 10 young gay and bisexual men aged 18 to 29 were examined to explore how young gay and bisexual men make decisions regarding sexual behaviors in the age of AIDS. Three main themes emerged: (a) disconnections between what an individual knows about HIV, their motivations to remain HIV-negative, and their sexual behaviors; (b) a struggle to connect emotionally and intimately with another man; and (c) a power dynamic whereby the individual acts as an autonomous decider in the decision-making process. Participants indicated high levels of HIV knowledge, and were engaged in a struggle to balance emotional experiences with sexual partners in a complex gendered dynamic. Findings from this analysis indicate a need to reexamine the social-cognitive theoretical frameworks that have guided gay men's HIV-prevention efforts, as these frameworks have failed to account for the psychologically complex emotional experiences and gender dynamics that are part of sexual decision making.


Subject(s)
Bisexuality/psychology , Emotions , HIV Infections/psychology , Homosexuality, Male/psychology , Safe Sex/psychology , Unsafe Sex/psychology , Adolescent , Adult , Cross-Sectional Studies , HIV Infections/prevention & control , Health Knowledge, Attitudes, Practice , Humans , Interview, Psychological , Male , Models, Psychological , Young Adult
15.
J Chromatogr A ; 1284: 17-27, 2013 Apr 05.
Article in English | MEDLINE | ID: mdl-23453463

ABSTRACT

This paper presents an integrated experimental and modelling approach to evaluate the potential of semi-continuous chromatography for the capture of monoclonal antibodies (mAb) in clinical and commercial manufacture. Small-scale single-column experimental breakthrough studies were used to derive design equations for the semi-continuous affinity chromatography system. Verification runs with the semi-continuous 3-column and 4-column periodic counter current (PCC) chromatography system indicated the robustness of the design approach. The product quality profiles and step yields (after wash step optimisation) achieved were comparable to the standard batch process. The experimentally-derived design equations were incorporated into a decisional tool comprising dynamic simulation, process economics and sizing optimisation. The decisional tool was used to evaluate the economic and operational feasibility of whole mAb bioprocesses employing PCC affinity capture chromatography versus standard batch chromatography across a product's lifecycle from clinical to commercial manufacture. The tool predicted that PCC capture chromatography would offer more significant savings in direct costs for early-stage clinical manufacture (proof-of-concept) (∼30%) than for late-stage clinical (∼10-15%) or commercial (∼5%) manufacture. The evaluation also highlighted the potential facility fit issues that could arise with a capture resin (MabSelect) that experiences losses in binding capacity when operated in continuous mode over lengthy commercial campaigns. Consequently, the analysis explored the scenario of adopting the PCC system for clinical manufacture and switching to the standard batch process following product launch. The tool determined the PCC system design required to operate at commercial scale without facility fit issues and with similar costs to the standard batch process whilst pursuing a process change application. A retrofitting analysis established that the direct cost savings obtained by 8 proof-of-concept batches would be sufficient to pay back the investment cost of the pilot-scale semi-continuous chromatography system.


Subject(s)
Chromatography, Affinity/instrumentation , Chromatography, Affinity/methods , Animals , Antibodies, Monoclonal/isolation & purification , Chromatography, Affinity/economics , Equipment Design , Humans , Mice , Sodium Chloride/chemistry , Technology, Pharmaceutical/instrumentation , Technology, Pharmaceutical/methods , Time Factors
16.
Biotechnol Bioeng ; 110(1): 206-19, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22806692

ABSTRACT

This article evaluates the current and future potential of batch and continuous cell culture technologies via a case study based on the commercial manufacture of monoclonal antibodies. The case study compares fed-batch culture to two perfusion technologies: spin-filter perfusion and an emerging perfusion technology utilizing alternating tangential flow (ATF) perfusion. The operational, economic, and environmental feasibility of whole bioprocesses based on these systems was evaluated using a prototype dynamic decision-support tool built at UCL encompassing process economics, discrete-event simulation and uncertainty analysis, and combined with a multi-attribute decision-making technique so as to enable a holistic assessment. The strategies were compared across a range of scales and titres so as to visualize how their ranking changes in different industry scenarios. The deterministic analysis indicated that the ATF perfusion strategy has the potential to offer cost of goods savings of 20% when compared to conventional fed-batch manufacturing processes when a fivefold increase in maximum viable cell densities was assumed. Savings were also seen when the ATF cell density dropped to a threefold increase over the fed-batch strategy for most combinations of titres and production scales. In contrast, the fed-batch strategy performed better in terms of environmental sustainability with a lower water and consumable usage profile. The impact of uncertainty and failure rates on the feasibility of the strategies was explored using Monte Carlo simulation. The risk analysis results demonstrated the enhanced robustness of the fed-batch process but also highlighted that the ATF process was still the most cost-effective option even under uncertainty. The multi-attribute decision-making analysis provided insight into the limited use of spin-filter perfusion strategies in industry. The resulting sensitivity spider plots enabled identification of the critical ratio of weightings of economic and operational benefits that affect the choice between ATF perfusion and fed-batch strategies.


Subject(s)
Batch Cell Culture Techniques/instrumentation , Batch Cell Culture Techniques/methods , Bioreactors , Biotechnology/instrumentation , Biotechnology/methods , Models, Biological , Antibodies, Monoclonal/metabolism , Batch Cell Culture Techniques/economics , Biotechnology/economics , Cells, Cultured , Computer Simulation , Monte Carlo Method , Perfusion , Stochastic Processes
17.
Subst Use Misuse ; 47(1): 12-21, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22049917

ABSTRACT

This study reveals associations between alcohol use and demographic variables, as well as the relation between alcohol use and sexual activity, using episodic data. Data were obtained during summer and fall 2008 from a sample of 558 gay, bisexual, and other young men who have sex with men (YMSM), ages of 13-29 years in New York City. Recruitment strategies targeted potential participants at gay-related venues and public spaces often frequented by YMSM. Alcohol use varied by race/ethnicity, with White YMSM consuming significantly more alcohol than other races/ethnicities. Participants over the age of 21 drank significantly more alcohol than participants ages 13-20. Alcohol use was not found to be associated with sexual risk-taking activity. Our findings are enriched by a large, diverse sample of urban YMSM. Study limitations are noted.


Subject(s)
Alcohol Drinking/epidemiology , Bisexuality , Homosexuality, Male , Sexual Behavior/statistics & numerical data , Adolescent , Adult , Age Factors , Alcohol Drinking/ethnology , Humans , Male , New York City/epidemiology , Prevalence , Risk-Taking , Young Adult
18.
Paediatr Anaesth ; 21(12): 1185-91, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21831111

ABSTRACT

BACKGROUND: Cardiopulmonary bypass (CPB)-associated renal dysfunction following cardiac surgery is well recognized. In patients with renal disease, cystatin C has emerged as a new biomarker which in contrast to creatinine (Cr) is sensitive to minor changes in glomerular filtration rate (GFR). AIM: We utilized cystatin C to investigate the association of CPB perfusion parameters with acute renal injury after pediatric cardiac surgery. METHODS: Twenty children, aged 4-58 months (AVSD, n = 7; VSD, n = 9; and ASD, n = 4), were prospectively studied. Glomerular filtration rate was quantified postoperatively by creatinine clearance (first and second 12-h periods; CrCl(0-12) and CrCl(12-24) ). Serum cystatin C and Cr were measured preoperatively and on days 0-3. Recorded CPB parameters included bypass duration (BP), perfusion pressure (PP), lowest pump flow (Q(min) ), lowest hematocrit, and corresponding lowest oxygen delivery (DO(2 min) ). Myocardial injury was determined by troponin-I. RESULTS: Postoperatively, GFR remained unchanged (CrCl(0-12) 63.6 ± 37.0 vs CrCl(12-24) 65.1 ± 27.5; P = 0.51) and only correlated with cystatin C (CrCl(0-12) vs cystatin C(Day 0) [r = 0.58, P = 0.018] and Cr(Day 0) [r = 0.09, P = 0.735]). Cr and cystatin C increased postoperatively to peak on days 2 and 3, respectively (Cr(PreOp) 31 ± 6.9 vs Cr(Day 2) 36.9 ± 12.2, P = 0.03; cystatin C(Day 0) 0.83 ± 0.27 vs cystatin C(Day 3) 1.45 ± 0.53, P = 0.02). Increased cystatin C was significantly associated with BP (P = 0.001), mean PP (P = 0.029), Q(min) (P = 0.005), troponin-I (P < 0.001), and DO(2 min) <300 ml·min(-1) ·m(-2) (P = 0.007). Receiver-operator cutoff >1.044 mg·l(-1) for cystatin C exhibited 100% sensitivity and 67% specificity for detecting renal dysfunction, defined as GFR <55 ml·min(-1) ·1.73 m(-2). CONCLUSIONS: Cystatin C is a sensitive marker of early renal dysfunction following pediatric heart surgery. Variations in bypass parameters, myocardial injury, and ultimately critical oxygen delivery are significantly associated with the degree of renal impairment.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Cystatin C/blood , Heart Diseases/blood , Postoperative Complications/blood , Renal Insufficiency/blood , Biomarkers/blood , Child, Preschool , Creatinine/blood , Female , Glomerular Filtration Rate , Heart Diseases/complications , Humans , Infant , Kidney Function Tests , Male , Prospective Studies , ROC Curve , Renal Insufficiency/complications , Sensitivity and Specificity , Troponin I/blood
19.
J Thorac Cardiovasc Surg ; 141(5): 1184-91, 2011 May.
Article in English | MEDLINE | ID: mdl-21397265

ABSTRACT

BACKGROUND: Right ventricular dysfunction occurs after tetralogy of Fallot repair and may relate to greater myocardial vulnerability to ischemia-reperfusion injury in cyanotic patients. The inducible form of heat shock protein 70 (HSP-70i), a molecular chaperone, is upregulated in response to cellular stress and limits myocardial injury against ischemia-reperfusion. We evaluated the myocardial expression of HSP-70i and its relation to right ventricular function and clinical outcome in patients with tetralogy of Fallot undergoing corrective surgery. METHODS: Twenty patients with tetralogy of Fallot were studied: 10 cyanotic (group Cy) and 10 noncyanotic (group noCy). Western blot was used to quantify HSP-70i from resected right ventricular outflow tract myocardium at baseline and subsequent ischemic time. Biventricular function was quantified by tissue Doppler echocardiography and compared with that of 15 age-matched healthy children. Postoperative systemic perfusion was assessed by mixed venous oxygen saturation, oxygen extraction ratio, and lactate. RESULTS: Group Cy had thicker septum (median 0.85 vs 0.66 cm; P = .01) and longer crossclamp time (median 100.0 vs 67.5 minutes; P = .004). There were no difference in HSP-70i between groups at baseline (4.12 vs 3.44 relative optical density; P = .45) or subsequent ischemic time. Preoperative biventricular systolic function was reduced in patients with tetralogy compared with controls with further postoperative right ventricular impairment. Group Cy had higher troponin-I levels (median 16.5 vs 11.1 ng/mL; P = .04) and inotrope scores (14.0 vs 6.5; P = .05) but no differences in ventricular function, mixed venous oxygen saturation, oxygen extraction ratio, and lactate between groups. In group Cy, baseline HSP-70i correlated with better postoperative right ventricular function (rho = 0.80; P = .009), mixed venous oxygen saturation (rho = 0.68; P = .04), and oxygen extraction ratio (rho = -0.71; P = .03). These relationships were absent in group noCy. CONCLUSIONS: The association of HSP-70i expression with improved right ventricular function and systemic perfusion suggests an important cardioprotective effect of HSP-70i in cyanotic tetralogy of Fallot.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Cyanosis/etiology , HSP72 Heat-Shock Proteins/metabolism , Myocardium/metabolism , Tetralogy of Fallot/surgery , Ventricular Dysfunction, Right/prevention & control , Ventricular Function, Right , Blood Gas Analysis , Blotting, Western , Case-Control Studies , Child, Preschool , Cyanosis/diagnostic imaging , Cyanosis/metabolism , Echocardiography, Doppler , Female , Hemodynamics , Humans , Infant , Male , Scotland , Tetralogy of Fallot/complications , Tetralogy of Fallot/diagnostic imaging , Tetralogy of Fallot/metabolism , Time Factors , Treatment Outcome , Troponin I/metabolism , Up-Regulation , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/metabolism , Ventricular Dysfunction, Right/physiopathology
20.
Subst Use Misuse ; 46(2-3): 264-73, 2011.
Article in English | MEDLINE | ID: mdl-21303246

ABSTRACT

This literature review considers the historical significance, emergence of, and interplay between the HIV and illicit drug use epidemics among gay, bisexual, and other men who have sex with men (MSM) in New York City (NYC). The continual rise in HIV infections in recent years among MSM, particularly among young MSM (YMSM), commands a need for the examination of the effectiveness of current HIV prevention strategies and a more comprehensive understanding of the complex biopsychosocial influences that place YMSM at risk. A chronological perspective of both the HIV and illicit drug use epidemics affecting NYC MSM is presented, followed by a review of the existing research on the synergistic relation between the two. Special consideration is given to the patterns and interconnectivity between HIV, substance use, and housing instability specific to YMSM, as they represent the demographic currently at greatest risk for HIV transmission in NYC. Thereafter, an overview of treatment research is provided. We conclude by offering recommendations for future research and best practices as we move forward in an attempt to reduce the incidence of HIV transmission.


Subject(s)
HIV Infections/epidemiology , Homosexuality, Male/statistics & numerical data , Substance-Related Disorders/epidemiology , Adult , Humans , Male , New York City , Risk-Taking , Sexual Behavior
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