Inpatient Hepatitis C Treatment Coordination and Initiation for Patients Who Inject Drugs.

BACKGROUND: With hepatitis C (HCV) incidence rising due to injection drug use, people who inject drugs (PWID) are a priority population for direct-acting antivirals (DAA). However, significant barriers exist. At our institution, hospitalized PWID were screened for HCV but not effectively linked to care. AIM: To improve retention in HCV care among hospitalized PWID. SETTING: Quaternary academic center in the Southeast US from August 2021 through August 2022. PARTICIPANTS: Hospitalized PWID with HCV. PROGRAM DESCRIPTION: E-consultation-prompted care coordination and HCV treatment with outpatient telehealth. PROGRAM EVALUATION: Care cascades were constructed to assess retention and HCV treatment, with the primary outcome defined as DAA completion or sustained virologic response after week 4. Of 28 patients, 11 started DAAs inpatient, 8 initiated outpatient, and 9 were lost to follow-up or transferred care. Overall, 82% were linked to care and 52% completed treatment. For inpatient initiators, 73% achieved the outcome. Of non-inpatient initiators, 71% were linked to care, 53% started treatment, and 36% achieved the outcome. DISCUSSION: Inpatient HCV treatment coordination, including DAA initiation, and telehealth follow-up, was feasible and highly effective for hospitalized PWID. Future steps should address barriers to inpatient DAA treatment and expand this model to other similar patient populations.

Tumor cell-specific retention of photosensitizers determines the outcome of photodynamic therapy for head and neck cancer.

Pheophorbide-based photosensitizers have demonstrated tumor cell-specific retention. The lead compound 3-[1'-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) in a clinical trial for photodynamic therapy of head and neck cancer lesions indicated a complete response in 80% of patients. The question arises whether the partial response in 20% of patients is due to inefficient retention of photosensitizers by tumor cells and, if so, can the photosensitizer preference of individual cancer cases be identified prior to photodynamic therapy. This study determined the specificity of head and neck cancer cells and tumor tissues for the uptake and retention of diffusible pheophorbides differing in peripheral groups on the macrocycle that contribute to cellular binding. The relationship between photosensitizer level and light-mediated photoreaction was characterized to identify markers for predicting the effectiveness of photodynamic therapy in situ. The experimental models were stromal and epithelial cells isolated from head and neck tumor samples and integrated into monotypic tissue cultures, reconstituted three-dimensional co-cultures, and xenografts. Tumor cell-specific photosensitizer retention patterns were identified, and a procedure was developed to allow the diagnostic evaluation of HPPH binding by tumor cells in individual cancer cases. The findings of this study may assist in designing conditions for photosensitizer application and photodynamic therapy of head and neck cancer lesions optimized for each patient's case.

Charged groups on pyropheophorbide-based photosensitizers dictate uptake by tumor cells and photodynamic therapy efficacy.

This study investigated the impact of anionic and cationic substituents of the pyropheophorbide-based photosensitizers (PS) on uptake and retention by tumor epithelial cells and photodynamic therapy (PDT). A series of PSs were generated that bear carboxylic acid functionalities, alkyl amines with variable length of carbon units or as a quaternary ammonium salt introduced at position 172 of 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH). The nature of the functionalities in the macrocycle made a significant difference in overall lipophilicity (log D values at pH 7.4), and in binding to and retention by human and murine tumor cells. Depending on the presence of functional groups, the PSs showed a change in cellular uptake from diffusion to endocytosis and in the preference for subcellular localization to mitochondria/ER or lysosomes. Two and more carboxylic groups drastically reduced uptake by all cell types. In contrast, PSs with amine and quaternary amine salt showed higher cellular binding, uptake and in vitro PDT efficacy than HPPH. The enhanced cellular uptake of the cationic PSs was accompanied by a loss of tumor cell specificity and contributed to severe systemic toxicity in tumor-bearing mice intravenously injected with the PS and subjected to investigate their therapeutic potential.

Tele-rehabilitation of upper-extremity hemiparesis after stroke: Proof-of-concept randomized controlled trial of in-home Constraint-Induced Movement therapy.

BACKGROUND: Although Constraint-Induced Movement therapy (CIMT) has been deemed efficacious for adults with persistent, mild-to-moderate, post-stroke upper-extremity hemiparesis, CIMT is not available on a widespread clinical basis. Impediments include its cost and travel to multiple therapy appointments. To overcome these barriers, we developed an automated, tele-health form of CIMT. OBJECTIVE: Determine whether in-home, tele-health CIMT has outcomes as good as in-clinic, face-to-face CIMT in adults ≥1-year post-stroke with mild-to-moderate upper-extremity hemiparesis. METHODS: Twenty-four stroke patients with chronic upper-arm extremity hemiparesis were randomly assigned to tele-health CIMT (Tele-AutoCITE) or in-lab CIMT. All received 35 hours of treatment. In the tele-health group, an automated, upper-extremity workstation with built-in sensors and video cameras was set-up in participants' homes. Internet-based audio-visual and data links permitted supervision of treatment by a trainer in the lab. RESULTS: Ten patients in each group completed treatment. All twenty, on average, showed very large improvements immediately afterwards in everyday use of the more-affected arm (mean change on Motor Activity Log Arm Use scale = 2.5 points, p < 0.001, d' = 3.1). After one-year, a large improvement from baseline was still present (mean change = 1.8, p < 0.001, d' = 2). Post-treatment outcomes in the tele-health group were not inferior to those in the in-lab group. Neither were participants' perceptions of satisfaction with and difficulty of the interventions. Although everyday arm use was similar in the two groups after one-year (mean difference = -0.1, 95% CI = -1.3-1.0), reductions in the precision of the estimates of this parameter due to drop-out over follow-up did not permit ruling out that the tele-health group had an inferior long-term outcome. CONCLUSIONS: This proof-of-concept study suggests that Tele-AutoCITE produces immediate benefits that are equivalent to those after in-lab CIMT in stroke survivors with chronic upper-arm extremity hemiparesis. Cost savings possible with this tele-health approach remain to be evaluated.

Adherence to National Consensus Guidelines and Association with Clinical Outcomes in Patients with Candidemia.

BACKGROUND: National consensus guidelines outline recommendations for best practices in treating patients with candidemia. This study evaluated the impact of receiving care adherent to the best practice recommendations on clinical outcomes in patients with candidemia. METHODS: This retrospective, multicenter study included patients with candidemia from 2010 to 2015 at 9 hospitals. The primary outcome was the composite of 30-day in-hospital mortality and 90-day candidemia recurrence. Outcomes were compared between those receiving and not receiving care adherent to the guideline recommendations. Inverse probability weights with regression adjustment were utilized to determine the average treatment effect of adherent care on the composite outcome. RESULTS: 295 patients were included with 14.2% meeting criteria for the composite outcome (11.9% mortality and 2.4% recurrence). The average treatment effect of adherent care was not significant (P = .75). However, receiving appropriate initial antifungal treatment and central venous catheter removal were both associated with the composite (average treatment effect of -17.5%, P = .011 and -8.8%, P = .013, respectively). In patients with a source of infection other than the central line, central venous catheter removal was not associated with the composite (P = .95). The most common reason for failure to receive appropriate initial antifungal treatment was omission of the loading dose. CONCLUSIONS: Central venous catheter removal and appropriate initial antifungal treatment were associated with a lower incidence of the composite of mortality and recurrence. Additional studies are needed to determine the optimal duration of therapy following candidemia clearance.

Clinical outcomes of Stenotrophomonas maltophilia infection treated with trimethoprim/sulfamethoxazole, minocycline, or fluoroquinolone monotherapy.

OBJECTIVES: The historical treatment of choice for Stenotrophomonas maltophilia infection is trimethoprim/sulfamethoxazole and this is primarily based on preclinical studies. The objective of this study was to examine the clinical outcomes of patients receiving monotherapy with different agents. METHODS: This was a retrospective study of adult patients receiving monotherapy for S. maltophilia infection with trimethoprim/sulfamethoxazole (TMP/SMX), a fluoroquinolone, or minocycline from 2010 to 2016. The primary outcome was clinical failure, a composite of recurrence, alteration of therapy due to adverse reaction or concern for clinical failure, or 30-day in-hospital mortality. The secondary outcome was 30-day in-hospital mortality. To account for treatment selection bias, multivariate regression and propensity score weighting were conducted. RESULTS: 284 patients were included (217 received TMP/SMX, 28 received a fluoroquinolone, and 39 received minocycline). The TMP/SMX and minocycline groups appeared to include similar patients whereas the fluoroquinolone group appeared to represent a slightly less severely ill population. Clinical failure was similar between groups (36%, 29%, and 31% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.69) as was 30-day mortality (15%, 7%, and 5% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.16). After controlling for confounding factors, receipt of minocycline (adjusted odds ratio [OR]=0.2 [0.1-0.7]) but not a fluoroquinolone (adjusted OR=0.3 [0.1 to 2.1]) was associated with lower mortality compared with TMP/SMX. This association persisted after propensity score weighting. CONCLUSIONS: Outcomes were similar or better with alternatives to TMP/SMX monotherapy, which indicates this may not be the treatment of choice for infections caused by S. maltophilia.

Peer-Led Education Expedites Deprescribing Proton Pump Inhibitors for Appropriate Veterans.

Costly proton pump inhibitors have been widely prescribed since the 1990s for prevention and treatment of ulcers and gastroesophageal reflux disease. Evidence published since 2012 demonstrates risks associated with taking proton pump inhibitors for longer than 8 weeks. Primary care providers mostly deprescribe proton pump inhibitors for persons not meeting criteria for long-term use. Many patients resist discontinuation.A 3-month evidence-based practice education project was conducted by a nurse practitioner to improve primary care provider peer deprescribing successes with appropriate patients in an outpatient California-based veteran primary care clinic. Fifteen primary care providers were pretested about usual care practices between 2 comparable clinics. Five primary care providers at the smaller clinic location were educated about long-term proton pump inhibitor use risks and introduced to 3 evidence-based practice guidelines using tapering techniques with follow-up care.A Canadian 2017 evidence-based practice proton pump inhibitor deprescribing guideline was proposed for translation into practice. Primary care providers voted to pilot this guideline, dependent upon nursing support. Primary care providers denied frustration with usual care practices, even as all were willing to try an evidence-based practice change between pre- and post-test surveys. Support for peer-led evidence-based practice on-site coaching increased from 87% to 100%. Tapering behavior increased from 67% to 100%, expediting improved long-term medication cessation.

Cell-specific Retention and Action of Pheophorbide-based Photosensitizers in Human Lung Cancer Cells.

This study determined in primary cultures of human lung cancer cells the cell specificity of chlorin-based photosensitizers. Epithelial cells (ECs) preferentially retained 3-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and related structural variants. Tumor-associated fibroblasts (Fb) differ from EC by a higher efflux rate of HPPH. Immunoblot analyses indicated dimerization of STAT3 as a reliable biomarker of the photoreaction. Compared to mitochondria/ER-localized photoreaction by HPPH, the photoreaction by lysosomally targeted HPPH-lactose showed a trend toward lower STAT3 cross-linking. Lethal consequence of the photoreaction differed between EC and Fb with the latter cells being more resistant. A survey of lung tumor cases indicated a large quantitative range by which EC retains HPPH. The specificity of HPPH retention defined in vitro could be confirmed in vivo in selected cases grown as xenografts. HPPH retention as a function of the tetrapyrrole structure was evaluated by altering side groups on the porphyrin macrocycle. The presence or absence of a carboxylic acid at position 172 proved to be critical. A benzyl group at position 20 enhanced retention in a subset of cancer cells with low HPPH binding. This study indicated experimental tools that are potentially effective in defining the photosensitizer preference and application for individual patient's cancer lesions.

Utilizing Buprenorphine in the Emergency Department after Overdose.

The United States is currently in the midst of an opioid epidemic. Barriers to treatment in the emergency department can lead to missed opportunities for helping prevent overdose and relapse in individuals with opioid use disorder. The administration of buprenorphine in the emergency department can potentially lead to better treatment outcomes for these individuals.

Evaluation of a Tool to Identify Child Sex Trafficking Victims in Multiple Healthcare Settings.

PURPOSE: Estimate the prevalence of child sex trafficking (CST) among patients seeking care in multiple healthcare settings; evaluate a short screening tool to identify victims in a healthcare setting. METHODS: This cross-sectional observational study involved patients from 16 sites throughout the U.S.: five pediatric emergency departments, six child advocacy centers, and five teen clinics. Participants included English-speaking youth ages 11-17 years. For emergency department sites, inclusion criteria included a chief complaint of sexual violence. Data on several domains were gathered through self-report questionnaires and examiner interview. Main outcomes included prevalence of CST among eligible youth; sensitivity, specificity, positive/negative predictive values, and positive/negative likelihood ratios for a CST screening tool. RESULTS: Eight hundred and ten participants included 91 (11.52%) youth from emergency departments, 395 (48.8%) from child advocacy centers, and 324 (40.0%) from teen clinics. Overall prevalence of CST was 11.1%: 13.2% among emergency department patients, 6.3% among child advocacy center patients, and 16.4% among teen clinic patients, respectively. The screen had a sensitivity, specificity, and positive likelihood ratio of 84.44% (75.28, 91.23), 57.50% (53.80, 61.11), and 1.99% (1.76, 2.25), respectively. CONCLUSIONS: This study demonstrates a significant rate of CST among patients presenting to emergency departments (for sexual violence complaints), child advocacy centers, and teen clinics. A six-item screen showed relatively good sensitivity and moderate specificity. Negative predictive value was high. Intervention for a "positive" screen may identify victims and help prevent high-risk youth from becoming victimized. This is one of the first CST screening tools specifically developed and evaluated in the healthcare setting.

Phase II Randomized Controlled Trial of Constraint-Induced Movement Therapy in Multiple Sclerosis. Part 1: Effects on Real-World Function.

BACKGROUND: Constraint-Induced Movement therapy (CIMT) has controlled evidence of efficacy for improving real-world paretic limb use in non-progressive physically disabling disorders (stroke, cerebral palsy). OBJECTIVE: This study sought to determine whether this therapy can produce comparable results with a progressive disorder such as multiple sclerosis (MS). We conducted a preliminary phase II randomized controlled trial of CIMT versus a program of complementary and alternative medicine (CAM) treatments for persons with MS, to evaluate their effect on real-world disability. METHODS: Twenty adults with hemiparetic MS underwent 35 hours of either CIMT or CAM over 10 consecutive weekdays. The primary clinical outcome was change from pretreatment on the Motor Activity Log (MAL). RESULTS: The CIMT group improved more on the MAL (2.7 points, 95% confidence interval 2.2-3.2) than did the CAM group (0.5 points, 95% confidence interval -0.1 to 1.1; P < .001). These results did not change at 1-year follow-up, indicating long-term retention of functional benefit for CIMT. The treatments were well tolerated and without adverse events. CONCLUSION: These results suggest that CIMT can increase real-world use of the more-affected arm in patients with MS for at least 1 year. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01081275.

Rehabilitation of stroke patients with plegic hands: Randomized controlled trial of expanded Constraint-Induced Movement therapy.

PURPOSE: To evaluate the efficacy of an expanded form of Constraint-Induced Movement Therapy (eCIMT) that renders CIMT, originally designed for treating mild-to-moderate upper-extremity hemiparesis, suitable for treating severe hemiparesis. METHODS: Twenty-one adults ≥1 year after stroke with severe upper-extremity hemiparesis (with little or no capacity to make movements with the more-affected hand) were randomly assigned to eCIMT (n = 10), a placebo-control procedure (n = 4), or usual care (n = 7). The participants who received usual care were crossed over to eCIMT four months after enrollment. The CIMT protocol was altered to include fitting of orthotics and adaptive equipment, selected neurodevelopmental techniques, and electromyography-triggered functional electrical stimulation. Treatment was given for 15 consecutive weekdays with 6 hours of therapy scheduled daily for the immediate eCIMT group and 3.5 hours daily for the cross-over eCIMT group. RESULTS: At post-treatment, the immediate eCIMT group showed significant gains relative to the combination of the control groups on the Grade-4/5 Motor Activity Log (MAL; mean = 1.5 points, P < 0.001, f = 4.2) and a convergent measure, the Canadian Occupational Performance Measure (COPM; mean = 2.3, P = 0.014, f = 1.1; f values ≥0.4 are considered large, on the COPM changes ≥2 are considered clinically meaningful). At 1-year follow-up, the MAL gains in the immediate eCIMT group were only 13% less than at post-treatment. The short and long-term outcomes of the crossover eCIMT group were similar to those of the immediate eCIMT group. CONCLUSIONS: This small, randomized controlled trial (RCT) suggests that eCIMT produces a large, meaningful, and persistent improvement in everyday use of the more-affected arm in adults with severe upper-extremity hemiparesis long after stroke. These promising findings warrant confirmation by a large RCT.

An enhanced protocol for constraint-induced aphasia therapy II: a case series.

PURPOSE: The initial version of Constraint-Induced Aphasia Therapy (CIAT I) consisted of a single exercise. This study sought to evaluate the feasibility for future trials of an expanded and restructured protocol designed to increase the efficacy of CIAT I. METHOD: The subjects were 4 native English speakers with chronic stroke who exhibited characteristics of moderate Broca's aphasia. Treatment was carried out for 3.5 hr/day for 15 consecutive weekdays. It consisted of 3 components: (a) intensive training by a behavioral method termed shaping using a number of expressive language exercises in addition to the single original language card game, (b) strong discouragement of attempts to use gesture or other nonverbal means of communication, and (c) a transfer package of behavioral techniques to promote transfer of treatment gains from the laboratory to real-life situations. RESULTS: Participation in speech in the life situation improved significantly after treatment. The effect sizes (i.e., d') in this domain were ≥ 2.2; d' values ≥ 0.8 are considered large. Improvement in language ability on a laboratory test, the Western Aphasia Battery-Revised (Kertesz, 2006), did not achieve statistical significance, although the effect size was large--that is, 1.3 (13.1 points). CONCLUSION: These pilot results suggest in preliminary fashion that CIAT II may produce significant improvements in everyday speech.

Method for enhancing real-world use of a more affected arm in chronic stroke: transfer package of constraint-induced movement therapy.

BACKGROUND AND PURPOSE: Constraint-induced movement therapy is a set of treatments for rehabilitating motor function after central nervous system damage. We assessed the roles of its 2 main components. METHODS: A 2 × 2 factorial components analysis with random assignment was conducted. The 2 factors were type of training and presence/absence of a set of techniques to facilitate transfer of therapeutic gains from the laboratory to the life situation (Transfer Package; TP). Participants (N=40) were outpatients ≥ 1-year after stroke with hemiparesis. The different treatments, which in each case targeted the more affected arm, lasted 3.5 hours/d for 10 weekdays. Spontaneous use of the more affected arm in daily life and maximum motor capacity of that arm in the laboratory were assessed with the Motor Activity Log and the Wolf Motor Function Test, respectively. RESULTS: Use of the TP, regardless of the type of training received, resulted in Motor Activity Log gains that were 2.4 times as large as the gains in its absence (P<0.01). These clinical results parallel previously reported effects of the TP on neuroplastic change. Both the TP and training by shaping enhanced gains on the Wolf Motor Function Test (P<0.05). The Motor Activity Log gains were retained without loss 1 year after treatment. An additional substudy (N=10) showed that a single component of the TP, weekly telephone contact with participants for 1 month after treatment, doubled Motor Activity Log scores at 6-month follow-up. CONCLUSIONS: The TP is a method for enhancing both spontaneous use of a more affected arm after chronic stroke and its maximum motor capacity. Shaping enhances the latter.

Constraint-induced movement therapy combined with conventional neurorehabilitation techniques in chronic stroke patients with plegic hands: a case series.

OBJECTIVE: To determine whether the combination of Constraint-Induced Movement Therapy (CIMT) and conventional rehabilitation techniques can produce meaningful motor improvement in chronic stroke patients with initially fisted hands. DESIGN: Case series. SETTING: University hospital outpatient laboratory. PARTICIPANTS: Consecutive sample (N=6) >1 year poststroke with plegic hands. INTERVENTIONS: Treatment consisted of an initial period of 3 weeks (phase A) when adaptive equipment in the home, orthotics, and splints were employed to improve ability to engage in activities of daily living. This was continued in phase B, when CIMT and selected neurodevelopmental treatment techniques were added. MAIN OUTCOME MEASURES: Motor Activity Log (MAL), accelerometry, Fugl-Meyer Motor Assessment (F-M). RESULTS: Patients exhibited a large improvement in spontaneous real-world use of the more-affected arm (mean lower-functioning MAL change=1.3±0.4 points; P<.001; d'=3.0) and a similar pattern of increase in an objective measure of real-world more-affected arm movement (mean change in ratio of more- to less-affected arm accelerometer recordings=0.12±0.1 points; P=.016; d'=1.2). A large improvement in motor status was also recorded (mean F-M change=5.3±3.3 points; P=.005; d'=1.6). CONCLUSIONS: The findings of this pilot study suggest that stroke patients with plegic hands can benefit from CIMT combined with some conventional rehabilitation techniques, even long after brain injury. More research is warranted.

Parents' perceptions of a pediatric palliative program.

Reports of family satisfaction with pediatric palliative care have been limited. This knowledge is critical for both program development and furthering understanding of needs. The purpose of this study was to assess parents' perceptions about whether a pediatric palliative care program was providing key elements of pediatric palliative care as described in the literature and to assess parental satisfaction with services. Data were collected from 65 parents, using a tool developed for the project, whose children died while receiving services from Rainbow Kids Palliative Care, a program of Primary Children's Medical Center, and the Department of Pediatrics, University of Utah, Salt Lake City, Utah. Respondents reported that the Rainbow Kids team had provided emotional support, helped with decision making and communication, and that their children's symptoms were managed. Furthermore, parent respondents expressed high levels of satisfaction with services from the Rainbow Kids team.

Constraint-induced movement therapy for the lower extremities in multiple sclerosis: case series with 4-year follow-up.

OBJECTIVE: To evaluate in a preliminary manner the feasibility, safety, and efficacy of Constraint-Induced Movement therapy (CIMT) of persons with impaired lower extremity use from multiple sclerosis (MS). DESIGN: Clinical trial with periodic follow-up for up to 4 years. SETTING: University-based rehabilitation research laboratory. PARTICIPANTS: A referred sample of ambulatory adults with chronic MS (N=4) with at least moderate loss of lower extremity use (average item score ≤6.5/10 on the functional performance measure of the Lower Extremity Motor Activity Log [LE-MAL]). INTERVENTIONS: CIMT was administered for 52.5 hours over 3 consecutive weeks (15 consecutive weekdays) to each patient. MAIN OUTCOME MEASURES: The primary outcome was the LE-MAL score at posttreatment. Secondary outcomes were posttreatment scores on laboratory assessments of maximal lower extremity movement ability. RESULTS: All the patients improved substantially at posttreatment on the LE-MAL, with smaller improvements on the laboratory motor measures. Scores on the LE-MAL continued to improve for 6 months afterward. By 1 year, patients remained on average at posttreatment levels. At 4 years, half of the patients remained above pretreatment levels. There were no adverse events, and fatigue ratings were not significantly changed by the end of treatment. CONCLUSIONS: This initial trial of lower extremity CIMT for MS indicates that the treatment can be safely administered, is well tolerated, and produces substantially improved real-world lower extremity use for as long as 4 years afterward. Further trials are needed to determine the consistency of these findings.

Cell-type selective phototoxicity achieved with chlorophyll-a derived photosensitizers in a co-culture system of primary human tumor and normal lung cells.

The ATP-dependent transporter ABCG2 exports certain photosensitizers (PS) from cells, implying that the enhanced expression of ABCG2 by cancer cells may confer resistance to photodynamic therapy (PDT) mediated by those PS. In 35 patient-derived primary cultures of lung epithelial and stromal cells, PS with different subcellular localization and affinity for ABCG2 displayed cell-type specific retention both independent and dependent on ABCG2. In the majority of cases, the ABCG2 substrate 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) was lost from fibroblastic cells more rapidly than from their epithelial counterparts, even in the absence of detectable ABCG2 expression, facilitating selective eradication by PDT of epithelial over fibroblastic cells in tumor/stroma co-cultures. Pairwise comparison of normal and transformed epithelial cells also identified tumor cells with elevated or reduced retention of HPPH, depending on ABCG2. Enhanced ABCG2 expression led to the selective PDT survival of tumor cells in tumor/stroma co-cultures. This survival pattern was reversible through HPPH derivatives that are not ABCG2 substrates or the ABCG2 inhibitor imatinib mesylate. PS retention, not differences in subcellular distribution or cell signaling responses, was determining cell type selective death by PDT. These data suggest that up-front knowledge of tumor characteristics, specifically ABCG2 status, could be helpful in individualized PDT treatment design.

Pharmaceutical approaches to eradication of persistent HIV infection.

Highly active antiretroviral therapy (HAART) has markedly decreased morbidity and mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals in the developed world. Successful therapy often results in stable plasma levels of HIV-1 RNA below the limits of detection of commercial assays. Nonetheless, HIV-1 has not been cured by HAART. The causes of persistence of HIV infection in the face of current therapy appear to be multifactorial: latent but replication-competent provirus in resting CD4+ T cells, cryptic viral expression below the limits of detection of clinical assays, and viral sanctuary sites might all contribute to persistence. Clearance of HIV infection will almost certainly require a multimodality approach that includes potent suppression of HIV replication, therapies that reach all compartments of residual HIV replication and depletion of any reservoirs of persistent, quiescent proviral infection. This review highlights the basic mechanisms for the establishment and maintenance of viral reservoirs and pharmaceutical approaches towards their elimination.