HIV transmission and retention in care among HIV‐exposed children enrolled in Malawi's prevention of mother‐to‐child transmission programme

Introduction : In Malawi, HIV‐infected pregnant and breastfeeding women are offered lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage (Option B+). Their HIV‐exposed children are enrolled in the national prevention of mother‐to‐child transmission (PMTCT) programme, but many are lost to follow‐up. We estimated the cumulative incidence of vertical HIV transmission, taking loss to follow‐up into account. Methods : We abstracted data from HIV‐exposed children enrolled into care between September 2011 and June 2014 from patient records at 21 health facilities in central and southern Malawi. We used competing risk models to estimate the probability of loss to follow‐up, death, ART initiation and discharge, and used pooled logistic regression and inverse probability of censoring weighting to estimate the vertical HIV transmission risk. Results : A total of 11,285 children were included; 9285 (82%) were born to women who initiated ART during pregnancy. At age 30 months, an estimated 57.9% (95% CI 56.6–59.2) of children were lost to follow‐up, 0.8% (0.6–1.0) had died, 2.6% (2.3–3.0) initiated ART, 36.5% (35.2–37.9) were discharged HIV‐negative and 2.2% (1.5–2.8) continued follow‐up. We estimated that 5.3% (95% CI 4.7–5.9) of the children who enrolled were HIV‐infected by the age of 30 months, but only about half of these children (2.6%; 95% CI 2.3–2.9) were diagnosed. Conclusions : Confirmed mother‐to‐child transmission rates were low, but due to poor retention only about half of HIV‐infected children were diagnosed. Tracing of children lost to follow‐up and HIV testing in outpatient clinics should be scaled up to ensure that all HIV‐positive children have access to early ART.     

Postnatal HIV transmission in breastfed infants of HIV‐infected women on ART: a systematic review and meta‐analysis

Introduction : To systematically review the literature on mother‐to‐child transmission in breastfed infants whose mothers received antiretroviral therapy and support the process of updating the World Health Organization infant feeding guidelines in the context of HIV and ART. Methods : We reviewed experimental and observational studies; exposure was maternal HIV antiretroviral therapy (and duration) and infant feeding modality; outcomes were overall and postnatal HIV transmission rates in the infant at 6, 9, 12 and 18 months. English literature from 2005 to 2015 was systematically searched in multiple electronic databases. Papers were analysed by narrative synthesis; data were pooled in random effects meta‐analyses. Postnatal transmission was assessed from four to six weeks of life. Study quality was assessed using a modified Newcastle‐Ottawa Scale (NOS) and GRADE. Results and discussion : Eleven studies were identified, from 1439 citations and review of 72 abstracts. Heterogeneity in study methodology and pooled estimates was considerable. Overall pooled transmission rates at 6 months for breastfed infants with mothers on antiretroviral treatment (ART) was 3.54% (95% CI: 1.15–5.93%) and at 12 months 4.23% (95% CI: 2.97–5.49%). Postnatal transmission rates were 1.08 (95% CI: 0.32–1.85) at six and 2.93 (95% CI: 0.68–5.18) at 12 months. ART was mostly provided for PMTCT only and did not continue beyond six months postpartum. No study provided data on mixed feeding and transmission risk. Conclusions : There is evidence of substantially reduced postnatal HIV transmission risk under the cover of maternal ART. However, transmission risk increased once PMTCT ART stopped at six months, which supports the current World Health Organization recommendations of life‐long ART for all.     

Botulinum toxin A submucosal injection for refractory non‐neurogenic overactive bladder: Early outcomes

The objective of the present study was to assess the short‐term effects of botulinum toxin A (BTX‐A) injection for refractory non‐neurogenic overactive bladder (OAB) in the setting of a prospective multicenter clinical trial. Refractory OAB was defined as persistent urgency urinary incontinence (UUI) ≥once a week despite taking anticholinergic agents, or the incapability to continue the agents because of the adverse effects. A total of 100 U of BTX‐A were reconstituted in 15 mL of normal saline and an aliquot of 0.5 mL was injected at 30 submucosal sites of the bladder wall. Nine men and eight women aged 67 ± 12 years were included. Subjective daytime frequency, urgency and UUI significantly decreased after treatment. On a 3‐day frequency‐volume chart, the daytime and night‐time frequency of UUI significantly decreased from 5.5 and 0.5 pre‐injection to 2.0 and 0.3 postinjection, respectively. Daytime urinary incontinence completely disappeared in six subjects. A urodynamic study showed the disappearance of detrusor overactivity in eight patients and a decrease in five patients. Maximum bladder capacity significantly increased from 179.9 to 267.3 mL. Difficulty on micturition or feeling of incomplete emptying was reported by 23.5% and 43.8% of patients at weeks 2 and 4, respectively. Postvoid residual urine increased to >100 mL in seven patients and >200 mL in one patient after injection; however, none of the patients required clean intermittent catheterization. These findings suggest promising efficacy of BTX‐A in Japanese OAB patients.     

Bacillus Calmette–Guérin treatment of non‐muscle invasive bladder cancer

Bacillus Calmette–Guérin (BCG) has been used in the intravesical treatment of non‐muscle invasive bladder cancer (NMIBC) for nearly 35 years; however, its use is still subject to controversy. The objective of this paper is to review the role of BCG in the treatment of patients with NMIBC. Clinical trials, meta‐analyses and guidelines related to the administration, safety and efficacy of intravesical BCG were reviewed. Intravesical BCG is more effective than intravesical chemotherapy in decreasing the risk of recurrence and progression to muscle invasive disease; however, it is associated with more local and systemic side‐effects. It is the gold standard in patients at high risk of progression. Maintenance BCG is required in order to achieve the best therapeutic results; however, the optimal dose, induction and maintenance schedules, and duration of treatment are unknown and might be different for each patient. Patients failing BCG treatment have a poor prognosis, and cystectomy is then the recommended treatment. Patients at low risk of recurrence and progression should not receive BCG, because of its side effects. Intermediate‐risk patients might be treated with either intravesical chemotherapy or BCG; however, for patients at high risk of progression, BCG is recognized as the treatment of choice. Further research is urgently needed to identify markers associated with BCG failure and to develop effective alternatives to cystectomy in patients failing BCG.     

Multicentre analysis of second‐line antiretroviral treatment in HIV‐infected children: adolescents at high risk of failure

Introduction : The number of HIV‐infected children and adolescents requiring second‐line antiretroviral treatment (ART) is increasing in low‐ and middle‐income countries (LMIC). However, the effectiveness of paediatric second‐line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second‐line ART outcomes for children and assessed the need for paediatric third‐line ART. Methods : We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second‐line ART in LMIC, contacting the corresponding study groups and including patient‐level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second‐line treatment. Results : We included 12 cohorts representing 928 children on second‐line protease inhibitor (PI)‐based ART in 14 countries in Asia and sub‐Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person‐years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first‐line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months). Conclusions : In LMIC, paediatric PI‐based second‐line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI‐based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.     

Microcomputed tomography imaging in a rat model of delayed union/non‐union fracture

We aimed to develop a clinically relevant delayed union/non‐union fracture model to evaluate a cell therapy intervention repair strategy. Histology, three‐dimensional (3D) microcomputed tomography (micro‐CT) imaging and mechanical testing were utilized to develop an analytical protocol for qualitative and quantitative assessment of fracture repair. An open femoral diaphyseal osteotomy, combined with periosteal diathermy and endosteal excision, was held in compression by a four pin unilateral external fixator. Three delayed union/non‐union fracture groups established at 6 weeks—(a) a control group, (b) a cell therapy group, and (c) a group receiving phosphate‐buffered saline (PBS) injection alone—were examined subsequently at 8 and 14 weeks. The histological response was combined fibrous and cartilaginous non‐unions in groups A and B with fibrous non‐unions in group C. Mineralized callus volume/total volume percentage showed no statistically significant differences between groups. Endosteal calcified tissue volume/endosteal tissue volume, at the center of the fracture site, displayed statistically significant differences between 8 and 14 weeks for cell and PBS intervention groups but not for the control group. The percentage load to failure was significantly lower in the control and cell treatment groups than in the PBS alone group. High‐resolution micro‐CT imaging provides a powerful tool to augment characterization of repair in delayed union/non‐union fractures together with outcomes such as histology and mechanical strength measurement. Accurate, nondestructive, 3D identification of mineralization progression in repairing fractures is enabled in the presence or absence of intervention strategies. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:729–736, 2008     

No in vivo infection of triple immunosuppressed non‐human primates after inoculation with high titers of porcine endogenous retroviruses*

Abstract: Background: Porcine endogenous retroviruses (PERVs) released from pig tissue can infect selected human cells in vitro and therefore represent a safety risk for xenotransplantation using pig cells, tissues, or organs. Although PERVs infect cells of numerous species in vitro, attempts to establish reliable animal models failed until now. Absence of PERV transmission has been shown in first experimental and clinical xenotransplantations; however, these trials suffered from the absence of long‐term exposure (transplant survival) and profound immunosuppression. Methods: We conducted infectivity studies in rhesus monkeys, pig‐tailed monkeys, and baboons under chronic immunosuppression with cyclosporine A, methylprednisolone, and the rapamycin derivative. These species were selected because they are close to the human species and PERVs can be transmitted in vitro to cells of these species. In addition, the animals received twice, a C1 esterase inhibitor to block complement activation before inoculation of PERV. In order to overcome the complications of microchimerism, animals were inoculated with high titers of cell‐free PERV. In addition, to enable transmission via cell–cell contact, some animals also received virus‐producing cells. For inoculation the primate cell‐adapted strain PERV/5° was used which is characterized by a high infectious titer. Produced on human cells, this virus does not express alpha 1,3 Gal epitopes, does not contain porcine antigens on the viral surface and is therefore less immunogenic in non‐human primates compared with pig cell‐derived virus. Finally, we present evidence that PERV/5° productively infects cells from baboons and rhesus monkeys. Results: In a follow‐up period of 11 months, no antibody production against PERV and no integration of proviral DNA in blood cells was observed. Furthermore, no PERV sequences were detected in the DNA of different organs taken after necropsy. Conclusion: These results indicate that in a primate model, in the presence of chronic immunosuppression, neither the inoculation of cell‐free nor cell‐associated PERV using a virus already adapted to primate cells results in an infection; this is despite the fact that peripheral blood mononuclear cells of the same animals are infectible in vitro.     

Oral 5‐aminolevulinic acid‐mediated photodynamic diagnosis using fluorescence cystoscopy for non‐muscle‐invasive bladder cancer: A multicenter phase III study

Objective

To confirm the reproducibility of the effectiveness and safety in photodynamic diagnosis of non‐muscle‐invasive bladder cancer using 5‐aminolevulinic acid in a prospective multicenter non‐randomized phase III trial.

Methods

A total of 61 patients with primary or recurrent non‐muscle‐invasive bladder cancer were prospectively enrolled from five hospitals between May 2015 and March 2016. 5‐Aminolevulinic acid (20 mg/kg) was orally administered 3 h before transurethral resection of bladder tumors using white light or fluorescent light. Of 60 evaluable patients, 511 specimens were obtained from tumor‐suspicious lesions and normal‐looking mucosa. The primary end‐point was sensitivity. The secondary end‐points were specificity, positive and negative predictive values, and safety.

Results

The sensitivity of the fluorescent light source (79.6%) was significantly higher (P < 0.001) than that of the white light source (54.1%). In total, 25.4% (46/181) of tumor specimens were diagnosed as positive with only the fluorescent light source. In nine (15%) of 60 patients, the risk classification and recommended treatment after transurethral resection of bladder tumors were changed depending on the additional types of tumor diagnosed by the fluorescent light source. The specificity of the fluorescent light versus white light source was 80.6% versus 95.5%. No grade 4–5 adverse event was noted. Hypotension and urticaria were severe adverse events whose relationship to oral 5‐aminolevulinic acid could not be excluded.

Conclusions

These findings confirm the diagnostic efficacy and safety of photodynamic diagnosis with 20 mg/kg of oral 5‐aminolevulinic acid, and show that transurethral resection of bladder tumors with a fluorescent light source using oral 5‐aminolevulinic acid is well tolerated.     

Recent progress in immune‐based interventions to prevent HIV‐1 transmission to children

Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV‐1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV‐1 infection. Thus, for the global community to achieve elimination of new paediatric HIV‐1 infections, innovative approaches need to be explored. Immune‐based approaches to prevention of mother‐to‐child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS‐free generation. Immune‐based interventions to prevent MTCT of HIV‐1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof‐of‐concept has been established over the last two decades that passively administered HIV‐1 Env‐specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune‐based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast‐Track 2030 goals to eliminate new paediatric HIV infections.     

Safety and efficacy of cryolipolysis for non‐invasive reduction of submental fat

Background and Objectives

Cryolipolysis has previously received FDA clearance for fat reduction in the abdomen, flanks, and thighs. There is also interest in small volume fat reduction for areas such as the chin, knees, and axilla. This article reports the results of a cryolipolysis pivotal IDE study for reduction of submental fullness.

Study Design/Material and Methods

A prototype small volume vacuum applicator (CoolMini applicator, CoolSculpting System, ZELTIQ Aesthetics) was used to treat 60 subjects in the submental area. At each treatment visit, a single treatment cycle was delivered at ?10°C for 60 minutes, the same temperature and duration used in current commercially‐available cryolipolysis vacuum applicators. At the investigator's discretion, an optional second treatment was delivered 6 weeks after the initial treatment. The primary efficacy endpoint was 80% correct identification of baseline photographs by independent physician review. The primary safety endpoint was monitoring incidence of device‐ and/or procedure‐related serious adverse events. Secondary endpoints included assessment of fat layer thickness by ultrasound and subject satisfaction surveys administered 12 weeks after final cryolipolysis treatment.

Results

Independent photo review from 3 blinded physicians found 91% correct identification of baseline clinical photographs. Ultrasound data indicated mean fat layer reduction of 2.0 mm. Patient questionnaires revealed 83% of subjects were satisfied, 80% would recommend submental cryolipolysis to a friend, 77% reported visible fat reduction, 77% felt that their appearance improved following the treatment, and 76% found the procedure to be comfortable. No device‐ or procedure‐related serious adverse events were reported.

Conclusion

The results of this clinical evaluation of 60 patients treated in a pivotal IDE study demonstrate that submental fat can be reduced safely and effectively with a small volume cryolipolysis applicator. Patient surveys revealed that submental cryolipolysis was well‐tolerated, produced visible improvement in the neck contour, and generated high patient satisfaction. These study results led to FDA clearance of cryolipolysis for submental fat treatment. Lasers Surg. Med. 48:3–13, 2016. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

     

Promoting safe infant feeding practices – the importance of structural,social and contextual factors in Southern Africa

There has been significant progress towards the goal of eliminating vertical transmission of HIV by 2015. However, a question that remains is how we can most effectively prevent late postnatal transmission of HIV through infant feeding. Guidelines published by the World Health Organization in 2010 have been widely adopted. These guidelines place strong emphasis on exclusive breastfeeding, in some countries over‐turning a prior emphasis on formula feeding. Where available, provision of antiretroviral treatment for HIV‐positive mothers or prophylaxis for infants offers additional protection against vertical transmission through infant feeding. However, merely changing guidelines is not sufficient to change practice, particularly with regard to culturally sanctioned forms of feeding, such as mixed feeding. This commentary highlights structural, social and contextual barriers to effective implementation of the guidelines and suggests ways to address some of these barriers.     

High self‐reported non‐adherence to antiretroviral therapy amongst adolescents living with HIV in Malawi: barriers and associated factors

Introduction : Globally adolescents and young adults account for more than 40% of new HIV infections, and HIV‐related deaths amongst adolescents increased by 50% from 2005 to 2012. Adherence to antiretroviral therapy (ART) is critical to control viral replication and preserve health; however, there is a paucity of research on adherence amongst the growing population of adolescents living with HIV/AIDS (ALHIV) in Southern Africa. We examined levels of self‐reported ART adherence, barriers to adherence, and factors associated with non‐adherence amongst ALHIV in Malawi. Methods : Cross‐sectional study of 519 ALHIV (12–18 years) attending two large HIV clinics in central and south‐eastern Malawi. Participants self‐reported missed doses (past week/month), barriers to adherence, and completed questionnaires on past traumatic events/stressors, disclosure, depression, substance use, treatment self‐efficacy, and social support. Biomedical data were retrieved from existing medical records. Multivariate logistic regression was performed to identify factors independently associated with self‐reported ART adherence (7 day recall). Results : The mean age of participants (SD) was 14.5 (2) years and 290 (56%) were female. Of the 519 participants, 153 (30%) reported having missed ART doses within the past week, and 234 (45%) in the past month. Commonly reported barriers to adherence included forgetting (39%), travel from home (14%), busy with other things (11%), feeling depressed/overwhelmed (6%), feeling stigmatized by people outside (5%) and within the home (3%). Factors found to be independently associated with missing a dose in the past week were drinking alcohol in the past month (OR 4.96, 95% CI [1.41–17.4]), missed clinic appointment in the past 6 months (OR 2.23, 95% CI [1.43–3.49]), witnessed or experienced violence in the home (OR 1.86, 95% CI [1.08–3.21]), and poor treatment self‐efficacy (OR 1.55 95% CI [1.02–2.34]). Sex and age were not associated with adherence. Conclusions : In our study, nearly half of all ALHIV reported non‐adherence to ART in the past month. Violence in the home or alcohol use in the past year as well as poor treatment self‐efficacy were associated with worse adherence. Sub‐optimal adherence is a major issue for ALHIV and compromise treatment outcomes. Programmes specifically tailored to address those challenges most pertinent to ALHIV may help improve adherence to ART.     

Long‐term survival after kidney transplantation in an HIV‐positive patient

Abstract: Only a decade ago, human immunodeficiency virus (HIV)‐seropositivity was considered an absolute contraindication for organ transplantation. With the currently available experience, it is no longer justified to deny HIV‐positive patients access to transplantation. To the best of our knowledge, we here present the longest surviving HIV‐positive patient after renal transplantation. The follow‐up period after renal transplantation in this HIV‐positive female is now 13 yr and she is in good general condition with excellent renal function. Throughout her post‐transplant follow‐up, we encountered a number of problems that are illustrative of the HIV‐positive patient.     

Post‐Weaning Multisystemic Wasting Syndrome and Other PCV2‐Related Problems in Pigs: a 12‐Year Experience

Post‐weaning multisystemic wasting syndrome (PMWS) and other porcine circovirus type 2 (PCV2)‐related diseases have been reported throughout the world for about 10 years. The present paper reviews the knowledge acquired in different fields and is largely based on the authors’ experience. The horizontal transmission of PCV2 is widely documented. Contact between pigs is the main route of transmission for both PCV2 and PMWS. However, experimental inoculation of PCV2 to pigs does not give consistent results and severe clinical signs as encountered in the field are rarely obtained. It is thus acknowledged that additional conditions are required for the disease to be severe in growing pigs. These are not all known but co‐infections are thought to act as triggers. The spread of such triggers/enhancers, which may or may not be infectious, could have played a role in PMWS dissemination via normal national and international trade, in some cases conferring an epidemic pattern to this spread. Most of the risk factors identified in surveys relate to poor biosecurity and inadequate hygiene/husbandry/herd management. The good correlation between viral burden in the tissues and disease severity emphasized the role of infection pressure. Genomic analysis showed great similarities between PCV2 isolates. However, although two main genotypes (genogroups) could be distinguished from the phylogenic trees, and changes with time, no clear relationship with strain virulence was apparent. Isolates detected in PMWS‐positive pigs could also be detected in healthy pigs from healthy farms. A strong sow effect was observed in disease expression in the offspring. Colostrum composition and colostrum intake are supposed to be key components of disease expression. Medication is relatively inefficient as a control measure. Commercial PCV2 vaccines are now becoming available. However, losses as a result of PMWS and PCV2‐related diseases are greatly reduced by applying appropriate hygiene and husbandry practices.     

Prevention of HIV‐1 infection 2013: glimmers of hope

The efficiency of transmission of HIV depends on the infectiousness of the index case and the susceptibility of those exposed. Infectiousness is dictated by the concentration of HIV‐1 in relevant fluids (regardless of route of transmission) and the viral genotype and phenotype. People newly infected with HIV‐1 (i.e. acute infection) and those with STI co‐infections excrete such a large concentration of virus as to be “hyperinfectious.” The actual transmission of HIV likely occurs in the first few hours after exposure. The probability of transmission may be as low as 1/10,000 episodes of intercourse or 1/10 sexual exposures when anal intercourse is practiced. The transmission of HIV is generally limited to one or a small number of founder variants which themselves may be “hyperinfectious.” Synergistic behavioural and biologic HIV prevention strategies have been developed and implemented. Safer sex includes limiting the number of sexual partners, use of male latex condoms, and structural interventions to reduce exposure. These strategies appear to have contributed to reduced HIV incidence in many countries. Biological interventions have proved catalytic: these include treatment of inflammatory cofactors, voluntary male circumcision and use of antiviral agents either for infected people (who can be rendered remarkably less contagious) or as pre‐ and post‐exposure prophylaxis (PrEP and PEP). Ecologic evidence suggests that broader, earlier antiviral treatment of HIV may be reducing incidence in some (but not all) populations. However, maximal benefit of HIV “treatment for prevention” and application of PrEP will likely require a program of universal “test and treat,” where many more infected patients are identified, linked to care, and treated very early in disease and for life. Community randomized trials designed to support this approach are under way in Africa. The “test and treat” prevention strategy is resource‐intensive and serves to emphasize research that searches for a cure for HIV infection so that people living with HIV can eventually reduce or stop treatment. Likewise, success in HIV prevention emphasizes the importance of development of an HIV vaccine, which remains focused on agents that may evoke CTL responses, antibody dependent cytotoxicity, and (perhaps most important) broad neutralizing antibodies. A human clinical trial (RV144) and animal experiments have provided hope, excitement and a roadmap for development of an HIV vaccine.     

The challenge of chronic lung disease in HIV‐infected children and adolescents

Until recently, little attention has been given to chronic lung disease (CLD) in HIV‐infected children. As the HIV epidemic matures in sub‐Saharan Africa, adolescents who acquired HIV by vertical transmission are presenting to health services with chronic diseases. The most common is CLD, which is often debilitating. This review summarizes the limited data available on the epidemiology, pathophysiology, clinical picture, special investigations and management of CLD in HIV‐infected adolescents. A number of associated conditions: lymphocytic interstitial pneumonitis, tuberculosis and bronchiectasis are well described. Other pathologies such as HIV‐associated bronchiolitis obliterans resulting in non‐reversible airway obstruction, has only recently been described. In this field, there are many areas of uncertainty needing urgent research. These areas include the definition of CLD, pathophysiological mechanisms and common pathologies responsible. Very limited data are available to formulate an effective plan of investigation and management.     

Prediction models for progression of non‐muscle‐invasive bladder cancer: A review

An accurate prediction of progression is critically important in the management of non‐muscle‐invasive bladder cancer. At present, three risk models are widely known for prediction of the risk of tumor recurrence and progression of non‐muscle‐invasive bladder cancer: the European Organization for Research and Treatment of Cancer, Club Urológico Español de Tratamiento Oncológico, and new European Organization for Research and Treatment of Cancer models. Bladder neck involvement has been shown to be one of the significant predictors for progression in non‐muscle‐invasive bladder cancer, and a new scoring model (Tokyo Medical and Dental University model) consisting of bladder neck involvement, tumor grade, and stage has been developed and externally validated. However, the predictive abilities of these models are still unsatisfactory, and more precise models are necessary for accurate individual prediction of prognosis. Until now, time‐fixed analysis has been used for most studies predicting the prognosis and outcome of non‐muscle‐invasive bladder cancer patients. In order to predict progression more precisely, time‐dependent models should be developed using multiple‐event analytical techniques, as non‐muscle‐invasive bladder cancer often progresses to muscle‐invasive bladder cancer after multiple recurrences and changes in tumor characteristics over a long natural history. Integration of molecular markers is also a promising approach. A validated model that accurately predicts the risk of progression would help urologists and patients decide whether and when to choose radical cystectomy on an individual basis.     

Antiviral re‐treatment of IFN‐Ribavirin non‐responders for recurrent post‐transplantation hepatitis C

Yedibela S, Demir R, Melling N, Aydin Ü, Schuppan D, Müller V, Hohenberger W, Schönleben F. Antiviral re‐treatment of IFN‐Ribavirin non‐responders for recurrent post‐transplantation hepatitis C.
Clin Transplant 2011: 25: 131–135. © 2010 John Wiley & Sons A/S. Abstract: Background: The aim of the study was to compare the efficacy and tolerability of pegylated interferon (PEG‐IFN) plus ribavirin (RIB) and PEG‐IFN monotherapy after unsuccessful initial therapy with interferon‐α2b (IFN) plus RIB after recurrent post‐transplantation hepatitis C. Methods: Twenty‐four patients with either no response (n = 10) or relapse (n = 14) after treatment with IFN plus RIB were prospectively randomized in the two treatment arms: 1) PEG‐IFN monotherapy at a dosage of 0.8 μg/kg per week (n = 12) and 2) PEG‐IFN (0.8 μg/kg per week) plus RIB (800–1200 mg/d) (n = 12). Results: Twenty‐one patients (86%) were treated for at least six months. Three patients are still being treated. At the end of therapy, 18 patients (75%) were HCV RNA negative. Five (45%) patients in PEG‐IFN and five (50%) in PEG‐IFN plus RIB arms had sustained virological response. Two patients (10%) died from recurrent hepatocellular carcinoma. The histologic activity indices significantly improved in both treatment arms. In the PEG‐IFN arm, one patient experienced an acute rejection and discontinued therapy. Conclusions: Both treatment arms showed to be effective, well tolerated and lead to an improvement in histologic outcome. Because of lower rates in side effects and equal outcome, PEG‐IFN monotherapy is an adequate option for antiviral re‐treatment.