Renal Embolization and Urothelial Sclerotherapy for Recurrent Obstructive Urosepsis and Intractable Haematuria from Upper Tract Urothelial Carcinoma

Management of intractable haematuria and obstructive urosepsis from upper tract urothelial carcinoma can be problematic in patients not suitable for surgery, chemotherapy or radiotherapy. Interventional radiology techniques provide alternative approaches in this setting, such as complete kidney embolization to cease urine output, percutaneous nephrostomy, antegrade injection of sclerotherapy agents and sterilisation of the upper collecting system. Related approaches have been successfully employed to sclerose renal cysts, lymphoceles, chyluria and intractable lower tract haemorrhage. No reports of percutaneous, antegrade sclerotherapy in the upper urinary tract have previously been published. We present a case of recurrent haematuria and obstructive urosepsis caused by invasive upper tract urothelial carcinoma in a non-operative patient, which was treated with renal embolisation and percutaneous upper tract urothelial sclerotherapy.     

Comparison of outcome of open reduction and internal fixation versus closed treatment in pediatric mandible fractures-a retrospective study

The aim of the study was to compare the outcome and complications of open reduction and internal fixation (ORIF) with closed treatment, as well as to review the literature. This was a retrospective study on pediatric patients with mandible fracture. The primary objective was a comparison of outcomes in terms of bone healing, maximal incisal opening (MIO), and occlusion, and the secondary objective was to review complications. A total of 77 pediatric patients (age <12 years) were managed with closed treatment and 23 with ORIF. In all, 62 patients were found with a single fracture (22 patients with parasymphysis fracture and 21 with condyle fracture, followed by symphysis, angle, and body fracture) and 38 patients with more than one fracture, with symphysis and bilateral condyle fracture being the most common. Bone healing was observed in all the patients. Mean MIO was 26.9 ± 2.8 mm and 29.3 ± 1.7 mm in the closed and ORIF group, respectively, and the difference was statistically nonsignificant (p = 0.5). One patient (1.3%) had deranged occlusion, and mobility was observed in one patient (1.3%) in the closed treatment group. Infection and nerve paresthesia were not seen in any patient at follow-up. Although closed treatment is preferred, as it preserves the soft tissue and periosteum, a displaced mandible fracture especially with co-existing condylar fracture should be treated by ORIF.     

Stem cell therapy: A clinical trial of stroke

Background

The alarming disability burden and a high prevalence rate of stroke in India has encouraged the researchers to develop regenerative therapies to reduce clinical deficits. This study evaluates safety, feasibility and efficacy of autologous mononuclear and mesenchymal cell transplantation in stroke patients evaluated on clinical scores and functional imaging (fMRI and DTI).

Methods

Forty (n = 40) stroke patients were recruited with the inclusion criteria as: 3 months to 2 years of index event, power of hand muscles of at least 2; Brunnstrom stage: 2–5; conscious and comprehendible. Fugl Meyer (FM), modified Barthel Index (mBI), Medical Research Council (MRC) grade for strength, Ashworth tone scale and functional imaging was used for assessments at baseline, 8 weeks and 24 weeks. 50–60 million cells in 250 ml saline were infused intravenously over 2–3 h.

Results

The safety test profile was normal with no mortality or cell related adverse reactions in stem cell patients. Among outcome parameters, only modified Barthel Index (mBI) showed statistical significant improvement (p < 0.05) in the stem cell group. An increased number of cluster activation in Brodmann areas BA 4, BA 6 was observed post stem cell infusion indicating neural plasticity.

Conclusion

Autologous intravenous stem cell therapy is safe and feasible. Stem cells act as “scaffolds” for neural transplantation and may aid in repair mechanisms in stroke.     

Dentofacial injuries in commercial motorcycle accidents in Cameroon: pattern and cost implication of care

Objective

To assess the pattern of dentofacial injuries in commercial motorcycle accidents among riders and passengers in Cameroon.

Methods

This was a hospital based study conducted in 6 out of 10 regional capitals in the months of December 2011 to September 2012. Analyzed information included age, gender, residence, role on the motorcycle (rider or passenger), type, pattern and month of injury, cost, duration and patient''s perception about the cost of treatment.

Results

A total of 387 patients were studied with majority of the patients being 21–30 years (39.8%), males (63.8%), passengers (57.3%) and urban dwellers (85.8%). Most of the injuries occurred in December (20.7%), January (19.4%) and February (20.2%). Soft tissue injuries were most frequent (91.2%) followed by trauma to the teeth (83.5%), of which 62.3% were tooth loss. Mandibular fracture was commoner than maxillary fracture; (45% versus 25.3%). A total of 44.2% of patients received their treatment as in-patients. The treatment of the dentofacial injuries among 64.3% of the patients lasted for more than a month. A total of 51.9% of the patients spent 100,000 francs ($200) or more for their treatment. More than half (51.4%) of the patients perceived the cost of treatment as expensive.

Conclusion

Dentofacial injuries in commercial motorcycle accidents necessitated hospital admission and lengthy treatment time with high attendant cost. Preventing these injuries will serves as a form of poverty reduction as money that will be used by the victim to better their life is not used to correct deformities or treat injuries.     

Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib

BCR-ABL overexpression and stem cell quiescence supposedly contribute to the failure of imatinib mesylate (IM) to eradicate chronic myeloid leukemia (CML). However, BCR-ABL expression levels of persisting precursors and the impact of long-term IM therapy on the clearance of CML from primitive and mature bone marrow compartments are unclear. Here, we have shown that the number of BCR-ABL-positive precursors decreases significantly in all bone marrow compartments during major molecular remission (MMR). More importantly, we were able to demonstrate substantially lower BCR-ABL expression levels in persisting MMR colony-forming units (CFUs) compared with CML CFUs from diagnosis. Critically, lower BCR-ABL levels may indeed cause IM insensitivity, because primary murine bone marrow cells engineered to express low amounts of BCR-ABL were substantially less sensitive to IM than BCR-ABL-overexpressing cells. BCR-ABL overexpression in turn catalyzed the de novo development of point mutations to a greater extent than chemical mutagenesis. Thus, MMR is characterized by the persistence of CML clones with low BCR-ABL expression that may explain their insensitivity to IM and their low propensity to develop IM resistance through kinase point mutations. These findings may have implications for future treatment strategies of residual disease in CML.     

Modeling suggests gene editing combined with vaccination could eliminate a persistent disease in livestock

Recent breakthroughs in gene-editing technologies that can render individual animals fully resistant to infections may offer unprecedented opportunities for controlling future epidemics in farm animals. Yet, their potential for reducing disease spread is poorly understood as the necessary theoretical framework for estimating epidemiological effects arising from gene-editing applications is currently lacking. Here, we develop semistochastic modeling approaches to investigate how the adoption of gene editing may affect infectious disease prevalence in farmed animal populations and the prospects and time scale for disease elimination. We apply our models to the porcine reproductive and respiratory syndrome (PRRS), one of the most persistent global livestock diseases to date. Whereas extensive control efforts have shown limited success, recent production of gene-edited pigs that are fully resistant to the PRRS virus have raised expectations for eliminating this deadly disease. Our models predict that disease elimination on a national scale would be difficult to achieve if gene editing was used as the only disease control. However, from a purely epidemiological perspective, disease elimination may be achievable within 3 to 6 y, if gene editing were complemented with widespread and sufficiently effective vaccination. Besides strategic distribution of genetically resistant animals, several other key determinants underpinning the epidemiological impact of gene editing were identified.

Novel genomic technologies such as gene editing offer promising opportunities to tackle some of the most pressing global challenges humanity faces today. They provide new prospects to solving emerging threats such as the global COVID-19 pandemic (1) as well as to long-standing global health issues such as the HIV/AIDS crisis (2) or malnutrition (3, 4), with minimal side effects. Besides the medical field, food production stands to gain most from widespread use of genome editing technologies. Currently 11% of the human population suffers malnourishment (5), and this is expected to increase with the projected growth of the human population to 10.9 billion by 2100 (42%) (6). Meeting the 60% increase of agricultural production needed to provide sustainable and nutritious diets will likely require transformative innovations to existing production methods (7). While genome-editing technologies have been applied widely in plant breeding to simultaneously improve production and resilience to diverse stressors (see ref. 8 for examples), their application in the livestock sector is still in its infancy, primarily due to technical limitations associated with the gene-editing process itself and the safe and fast dissemination of edits, as well as ethical and societal concerns (9). Nevertheless, breakthroughs in genetic modification of farm animals through genome editing start to emerge with drastic improvements in efficiency traits (10, 11), animal welfare (12), and disease resistance (13, 14). Improving disease resistance in livestock seems particularly pertinent, as infectious diseases affect the entire food production chain and its economic viability (15).The recent scientific breakthroughs in genome editing raise expectations for radical shifts in infectious disease control in livestock (14). Although many countries currently lack specific regulations covering the application of genome-edited animals in the food chain, this technology currently falls under genetically modified organism legislation in countries that have such processes. Reflecting this, we are seeing the rapid development of gene-editing regulations worldwide [see the Global Gene Editing Regulation Tracker (16) for an up-to-date status of gene-editing regulations per country]. Specifically, some countries have identified that some genome-editing strategies are exempt from regulatory approval. This is reflected in the recent announcement in Japan that a genome-edited seabream does not need to be regulated as no gene has been introduced into the genome (17, 18). These developments make it realistic that application of gene editing to help control infectious disease is likely in the near future. This prospect evokes pressing questions concerning the theoretical and practical feasibility of tackling diseases for which conventional control methods have failed. It is currently not known how to best implement gene-editing-induced disease resistance to achieve noticeable reduction in disease prevalence and possibly even eliminate the disease on a national scale, and on what time scale such ambitious goals could be achieved.These questions are impossible to address in an entirely hypothetical context since epidemiological characteristics affecting the spread of the disease in question and the dynamics of the dispersal of resistant animals within the population play important roles in the success of the scheme. In this study, we focus on a particular disease, porcine reproductive and respiratory syndrome (PRRS), for the development of a mathematical modeling framework to investigate the feasibility of the application of gene editing to achieve disease elimination. PRRS represents one of the most important infectious disease problems for the pig industry worldwide, with economic losses estimated at $2.5 billion per annum in the United States and Europe alone (19, 20). Despite extensive global control efforts, the disease continues to persist in national commercial pig populations, largely due to high genetic heterogeneity of the PRRS virus, PRRSV (21), and the associated limited effectiveness of all PRRS vaccines (22, 23) and limited reliability of diagnostic tests (24, 25). There is considerable natural genetic variation in pigs’ responses to PRRSV infection, but evidence to date suggests that no pig strain is naturally fully resistant to it (26). However, recent advances in gene editing of porcine macrophages, in which a simple disruption of the CD163 gene confers complete resistance to infection with PRRSV, may revolutionize future PRRS control (27–29).To exploit the full potential of gene editing for PRRS control, we here develop a theoretical proof-of-concept model to address a number of crucial research questions. To what extent can gene editing help reduce PRRS prevalence in national commercial pig populations? Is it possible to eliminate this disease through gene editing by creating a disease-resistant subpopulation adequately dispersed within the national susceptible population? If so, what proportion of pigs would have to be PRRSV-resistant and how would these animals need to be distributed across herds?It is unlikely that gene editing will fully replace existing control methods, such as widespread vaccination. Hence, we also use our model to investigate the epidemiological effects of gene editing and vaccination combined. Finally, we investigate how fast the required proportion of resistant animals could be introduced in a national commercial pig population, if gene editing was strictly limited to breeding programs and resistance alleles propagate to commercial pigs using current industry practices with their diverse technical limitations. This last question becomes particularly important for an RNA virus with a high evolutionary rate such as PRRSV, since escape mutants of the virus might limit the shelf-life of gene editing and vaccines in terms of effectiveness (14, 30).We address these questions with two linked simulation models: 1) an epidemiological model to simulate the effects of different disease control schemes on PRRS prevalence in a national commercial pig population and 2) a gene flow model to simulate the propagation of PRRSV resistance alleles from breeding programs that routinely carry out gene editing for PRRS resistance into the commercial population. The epidemiological model provides insight into the numbers and distribution of genetically resistant pigs required to eliminate PRRS under a range of realistic scenarios. The allele propagation model subsequently provides estimates for the time required to realistically produce this required number of genetically resistant pigs.Our proof-of-concept model provides quantitative estimates for how gene editing may reduce infectious disease prevalence in farm animals and the required time frame and criteria for eliminating a disease on a national level.     

Percutaneous retrieval of a proximally migrated common bile duct endoprosthesis from the right anterior duct

Common bile duct (CBD) endoprostheses that are inserted at endoscopy are in routine clinical use to decompress the obstructed biliary tract. This case describes the proximal migration of a CBD endoprosthesis into the right anterior duct. An attempt at endoscopic retrieval failed. The endoprosthesis was retrieved by a percutaneous transhepatic approach using an Amplatz goose‐neck snare. To the best of our knowledge, use of the Amplatz goose‐neck snare has not been reported for this application.