Quantitative MRI in myositis patients: comparison with healthy volunteers and radiological visual assessment.

AIM: To assess whether magnetic resonance imaging (MRI)-based measurements of T2, fat fraction, diffusion tensor imaging, and muscle volume can detect differences between the muscles of myositis patients and healthy controls, and to identify how they compare with semi-quantitative MRI diagnosis. MATERIALS AND METHODS: Sixteen myositis patients and 16 age- and gender-matched healthy controls underwent MRI of their thigh. Quantitative MRI measurements and radiologists' semi-quantitative scores were assessed. Strength was assessed using an isokinetic dynamometer. RESULTS: Fat fraction and T2 values were higher in myositis patients whereas muscle volume was lower compared to healthy controls. There was no difference in diffusion. Muscle strength was lower in myositis patients compared to healthy controls. In a subgroup of eight patients, scored as unaffected by radiologists, T2 values were still significantly higher in myositis patients. CONCLUSIONS: Quantitative MRI measurements can detect differences between myositis patients and healthy controls. Changes in the muscles of myositis patients, undetected by visual, semi-quantitative scoring, can be detected using quantitative T2 measurements. This suggests that MRI T2 values may be useful for the management of myositis patients.

The effect of ageing on skeletal muscle as assessed by quantitative MR imaging: an association with frailty and muscle strength.

BACKGROUND: Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. AIMS: To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. METHODS: 18 'young' (18-30 years), 18 'middle-aged' (31-68 years) and 18 'older' (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. RESULTS: Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. DISCUSSION: Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. CONCLUSIONS: Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle.

MRI in acute muscle tears in athletes: can quantitative T2 and DTI predict return to play better than visual assessment?

OBJECTIVES: To assess the ability of quantitative T2, diffusion tensor imaging (DTI) and radiologist's scores to detect muscle changes following acute muscle tear in soccer and rugby players. To assess the ability of these parameters to predict return to play times. METHODS: In this prospective, longitudinal study, 13 male athletes (age 19 to 34 years; mean 25 years) underwent MRI within 1 week of suffering acute muscle tear. Imaging included measurements of T2 and DTI parameters. Images were also assessed using modified Peetrons and British athletics muscle injury classification (BAMIC) scores. Participants returned for a second scan within 1 week of being determined fit to return to play. MRI measurements were compared between visits. Pearson's correlation between visit 1 measurements and return to play times was assessed. RESULTS: There were significant differences between visits in BAMIC scores (Z = - 2.088; p = 0.037), modified Peetrons (Z = - 2.530; p = 0.011) and quantitative MRI measurements; T2, 13.12 ms (95% CI, 4.82 ms, 21.42 ms; p = 0.01); mean diffusivity (0.22 (0.04, 0.39); p = 0.02) and fractional anisotropy (0.07 (0.01, 0.14); p = 0.03). BAMIC scores showed a significant correlation with return to play time (Rs = 0.64; p = 0.02), but modified Peetrons scores and quantitative parameters did not. CONCLUSIONS: T2 and DTI measurements in muscle can detect changes due to healing following muscle tear. Although BAMIC scores correlated well with return to play times, in this small study, quantitative MRI values did not, suggesting that T2 and DTI measurements are inferior predictors of return to play time compared with visual scoring. KEY POINTS: • Muscle changes following acute muscle tear can be measured using T2 and diffusion measurements on MRI. • Measurements of T2 and diffusion using MRI are not as good as a radiologist's visual report at predicting return to play time after acute muscle tear.

Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer.

BACKGROUND: Utilization of alternative transcription start sites through alterations in epigenetic promoter regions causes reduced expression of immunogenic N-terminal peptides, which may facilitate immune evasion in early gastric cancer. We hypothesized that tumors with high alternate promoter utilization would be resistant to immune checkpoint inhibition in metastatic gastric cancer. PATIENTS AND METHODS: Two cohorts of patients with metastatic gastric cancer treated with immunotherapy were analyzed. The first cohort (N = 24) included patients treated with either nivolumab or pembrolizumab. Alternate promoter utilization was measured using the NanoString® (NanoString Technologies, Seattle, WA, USA) platform on archival tissue samples. The second cohort was a phase II clinical trial of patients uniformly treated with pembrolizumab (N = 37). Fresh tumor biopsies were obtained, and transcriptomic analysis was carried out on RNAseq data. Alternate promoter utilization was correlated to T-cell cytolytic activity, objective response rate and survival. RESULTS: In the first cohort 8 of 24 (33%) tumors were identified to have high alternate promoter utilization (APhigh), and this was used to define the APhigh tertile of the second cohort (13 APhigh of 37). APhigh tumors exhibited decreased markers of T-cell cytolytic activity and lower response rates (8% versus 42%, P = 0.03). Median progression-free survival was lower in the APhigh group (55 versus 180 days, P = 0.0076). In multivariate analysis, alternative promoter utilization was an independent predictor of immunotherapy survival [hazard ratio 0.29, 95% confidence interval 0.099-0.85, P = 0.024). Analyzing tumoral evolution through paired pre-treatment and post-treatment biopsies, we observed consistent shifts in alternative promoter utilization rate associated with clinical response. CONCLUSION: A substantial proportion of metastatic gastric cancers utilize alternate promoters as a mechanism of immune evasion, and these tumors may be resistant to anti-PD1 immune checkpoint inhibition. Alternate promoter utilization is thus a potential mechanism of resistance to immune checkpoint inhibition, and a novel predictive biomarker for immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT#02589496.

Epidemiology and clinical characteristics of invasive mould infections: A multicenter, retrospective analysis in five Asian countries.

Formal, large-scale, multicenter studies of invasive mould infection (IMI) in Asia are rare. This 1-year, retrospective study was designed to assess the incidence and clinical determinants of IMI in centers in five countries (Thailand, Taiwan, Singapore, China, India). Patients treated in a single year (2012) were identified through discharge diagnoses, microbiology, and histopathology logs, and entered based on published definitions of IMI. A total of 155 cases were included (median age 54 years; 47.7% male). Of these, 47.7% had proven disease; the remainder had probable IMI. The most frequent host factors were prolonged steroid use (39.4%) and recent neutropenia (38.7%). Common underlying conditions included diabetes mellitus (DM; 30.9%), acute myeloid leukemia (19.4%), and rheumatologic conditions (11.6%). DM was more common in patients with no recent history of neutropenia or prolonged steroid use (P = .006). The lung was the most frequently involved site (78.7%), demonstrating a range of features on computed tomography (CT). Aspergillus was the most common mould cultured (71.6%), primarily A. fumigatus and A. flavus, although proportions varied in different centers. The most often used antifungal for empiric therapy was conventional amphotericin. Ninety-day mortality was 32.9%. This is the first multicenter Asian study of IMI not limited to specific patient groups or diagnostic methods. It suggests that DM and rheumatologic conditions be considered as risk factors for IMI and demonstrates that IMI should not be ruled out in patients whose chest features on CT do not fit the conventional criteria.

[Influence of postoperative pelvic floor function on different surgical procedures of hysterectomy].

Objective: To compare the influence of postoperative pelvic floor function after different surgical procedures of hysterectomy. Methods: A total of 260 patients who underwent hysterectomy in Renmin hospital of Wuhan University from January 2012 to January 2014 were enrolled in the study, and divided into 5 groups by different surgical procedures, which were total abdominal hysterectomy (A-TH; 46 cases), total laparoscopic hysterectomy (L-TH; 59 cases), total vaginal hysterectomy (V-TH; 42 cases), abdominal intrafascial hysterectomy (A-CISH; 78 cases), laparoscopic intrafascial hysterectomy (L-CISH; 35 cases). Pelvic examination, pelvic organ prolapse quantitation (POP-Q), test of pelvic muscle strength, pelvic floor distress inventory-short form 20 (PFDI-20) and the female sexual function index (FSFI) questionnaire were measured after 6 months and 12 months. Results: The differences of pelvic organ prolapse incidence after 6 months, A-TH and A-CISH [7% (3/46) versus 3% (2/78)], A-TH and L-CISH [7% (3/46) versus 3% (1/35)] were statistically significance (all P<0.05).POP-Q grade after 6 months between A-TH and A-CISH was statistically different in degree (P<0.05). The differences of incidence of abnormal pelvic floor muscle fatigue after 6 months of A-TH and A-CISH [59% (27/46) versus 29% (23/78)], A-TH and L-CISH [59% (27/46) versus 26% (9/35)] were statistically significant (all P<0.05), after 12 months the difference of L-TH and A-CISH [61% (36/59) versus 29%(23/78)] was statistically different (P<0.05). The differences of incidence of abnormal pelvic floor muscle strength after 6 months of L-TH and A-CISH [53% (31/59) verus 24% (19/78)], V-TH and A-CISH [60% (25/42) verus 24% (19/78)], V-TH and L-CISH [60% (25/42) verus 23% (8/35)] were statistically significant (all P<0.05); after 12 months the difference of V-TH and A-CISH [57% (24/42) versus 26%(20/78)] was statistically significant (P<0.05). Stress urinary incontinence, abnormal bowel movements after 6 months and 12 months were no significant difference between groups (all P>0.05), PFDI-20 total score was not statistically significant (P>0.05). FSFI total score after 6 months and 12 months in A-TH and A-CISH, L-TH and A-CISH, A-CISH and L-CISH were statistically significant (all P<0.05). Conclusion: The influences of different surgical procedures to pelvic floor function are no statistical difference; as to the surgical resection of hysterectomy, intrafascia hysterectomy compared with extrafascia hysterectomy, the former is more helpful to the protection of the structure and function of the pelvic floor.

Recurrent trichosporonosis with central nervous system involvement in an allogeneic hematopoietic stem cell transplant recipient.

Trichosporon is an ubiquitous yeast that has emerged as an opportunistic pathogen in the immunocompromised host. We describe a case of invasive trichosporonosis in an allogeneic hematopoietic stem cell transplant (allo-HSCT) recipient while on caspofungin antifungal prophylaxis. She developed disseminated trichosporonosis in the pre-engraftment period and was successfully treated with voriconazole. She later developed 2 further episodes of invasive trichosporonosis involving the central nervous system. This case highlights the challenges of managing trichosporonosis in allo-HSCT recipients and suggests the need for lifelong therapy in some patients.

[Value of using gonadotropin-releasing hormone agonist pretreatment in adenomyosis patients before adenomyomectomy].

Objective: To investigate the value of using gonadotropin-releasing hormone agonist (GnRH-a) pretreatment in adenomyosis patients before adenomyomectomy. Methods: From May 2012 to September 2015, 87 patients with adenomyosis who were non-effective to conservative therapy in Renmin Hospital of Wuhan University were enrolled in this study. According to the principle of randomized control, 41 patients were in the treatment group who were treated with GnRH-a 2-3 cycles before adenomyomectomy, while 46 patients in the control group. The control group paients were operated without any pretreatments. The blood loss, the number of penetrating into uterine cavity, duration of operation, duation of peritoneal drainage and the amount of drainage fluid, the difference of hemoglobin value before and after operation, total white blood cell count, duration of hospitalization, the maximum diameter of uterus and other indicators between the two groups were compared. Results: In the treatment group, before and after treatment with GnRH-a, the uterus size, blood hemoglobinand CA125 value were statistically different (all P<0.05); between the treatment group of GnRH-a treated for 2 cycles and for 3 cycles, there were statistical differences of blood hemoglobin value [(108 ± 20) versus (118 ± 24) g/L], CA125 value [(26 ± 11) versus(19 ± 4) kU/L; all P< 0.05]. There were statistical differences of blood loss in operation [(113 ± 32) versus (194 ± 42) ml], ratio of penetrating into uterine cavity [12% (5/41) versus 12% (8/46)], duration of operation[(79±23) versus (91±25) minutes], duration of peritoneal drainage after operation [(2.1±0.9) versus (3.0±1.2) days] and the amount of drainage fluid [(152±43) versus (232±32) ml], the difference of hemoglobin value before and after surgery [(-15.6±2.9) versus (-23.7±3.5) g/L], white blood cell count after 2-3 days of operation [(11.4±4.2)×109/L versus (13.5 ± 3.2) × 109/L], ratio of peri-operative blood transfusion [5% (2/41) versus 20% (9/46)] and duration of hospitalization [(11.2±1.9) versus (13.6±3.1) days] between the treatment group and the control group (all P<0.05). Conclusion: The pretreatment of using GnRH-a before adenomyomectomy in adenomyosis patients has benefits for implementation of surgery and reducing peri-operative and postoperative complications.

Role of vascular channels as a novel mechanism for subchondral bone damage at cruciate ligament entheses in osteoarthritis and inflammatory arthritis.

OBJECTIVES: The purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA). METHODS: Normal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion. RESULTS: Vascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%). CONCLUSION: The findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.

Chemotherapy extravasation at hospital pulau pinang, malaysia.

PURPOSE: Extravasation with intravenous chemotherapy is a common complication of chemotherapy which carries the risk of devastating complications. This study aims to determine the rate of extravasation with intravenous chemotherapy in a major hospital where chemotherapy is delivered in various departments other than the oncology department. PATIENTS AND METHODS: All patients who underwent intravenous chemotherapy in the oncology department and surgical wards in Penang General hospital from 1st February 2008 till 31st June 2008 were recruited retrospectively for this study to look at the rate of extravasation. RESULTS: A total of 602 patients underwent intravenous chemotherapy during this period. Fifty patients received chemotherapy in the general surgical ward while another 552 patients received chemotherapy in the oncology department. There were 5 cases of extravasation giving an overall extravasation rate of 0.8% (5/602). however, 4 of these cases occurred in the general surgical ward giving it a rate of 8% (4/50). CONCLUSION: The rate of extravasation in our hospital was 0.8%. however, this rate can be significantly increased if it is not done under a specialized unit delivering intravenous chemotherapy on a regular basis. Preventive steps including a standard chemotherapy delivery protocol, staff and patient education must be put in place in all units delivering intravenous chemotherapy.

Opportunities and challenges for biomarker discovery using electronic health record data.

Electronic health records (EHRs) have become increasingly relied upon as a source for biomedical research. One important research application of EHRs is the identification of biomarkers associated with specific patient states, especially within complex conditions. However, using EHRs for biomarker identification can be challenging because the EHR was not designed with research as the primary focus. Despite this challenge, the EHR offers huge potential for biomarker discovery research to transform our understanding of disease etiology and treatment and generate biological insights informing precision medicine initiatives. This review paper provides an in-depth analysis of how EHR data is currently used for phenotyping and identifying molecular biomarkers, current challenges and limitations, and strategies we can take to mitigate challenges going forward.

Repeatability of quantitative MRI in patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) affects 1% of the population and is principally associated with joint inflammation. It is suggested however that muscle involvement may be one of the earliest clinical features of RA. It is therefore important that techniques exist to accurately assess muscle health in those with RA to enable successful treatment. This study assesses the inter-rater and intra-rater repeatability of Diffusion Tensor MRI (DTI), 2-Point Dixon fat fraction, and T2 relaxation of the thigh muscle in patients with RA using manual regions of interest (ROI). METHODS: Nineteen patients (10/19 males; mean age 59; range 18-85) diagnosed with RA had an MRI scan of their hamstrings and quadriceps muscles to obtain fat fraction (FF), mean diffusivity (MD), fractional anisotropy (FA), and T2 quantitative measurements. Two raters DB & MF independently contoured ROIs for each patient. DB repeated the ROI for the same 19 patients after a 6-month hiatus to assess intra-rater repeatability. Inter-rater and intra-rater repeatability for the ROI measurements were compared using Inter Class Correlation (ICC) and Bland-Altman plots. RESULTS: There was excellent agreement for both inter-rater and intra-rater repeatability. ICC results ranged from 0.900 to 0.998 (P < 0.001), and intra-rater ICC results ranged from 0.977 to 0.999 (P < 0.001). Bland-Altman plots also showed excellent agreement. CONCLUSIONS: ICC measurements and Bland-Altman plots showed excellent repeatability and agreement with no statistically significant differences when assessing the inter-rater and intra-rater repeatability of FF, MD, FA, and T2 relaxation of the thigh muscle using manual regions of interest in patients with RA. IMPLICATIONS FOR PRACTICE: Manual ROI drawing does not introduce significant errors obtaining FF, MD, FA, and T2 MRI measurements in an RA population.

Magnetic resonance imaging in the assessment of metacarpophalangeal joint disease in early psoriatic and rheumatoid arthritis.

OBJECTIVES: The aim of this study was to determine whether magnetic resonance imaging (MRI)-related entheseal changes including osteitis and extracapsular oedema could be used to differentiate between metacarpophalangeal (MCP) joint involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: Twenty patients (10 each with early RA and PsA) had dynamic contrast-enhanced MRI (DCE-MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using quantitative analysis including the degree and kinetics of enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone oedema were scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) proposals. Entheseal-related features including extracapsular soft tissue enhancement or regions of diffuse bone oedema were also evaluated. RESULTS: MRI was not able to differentiate at the group level between both cohorts on the basis of entheseal-related disease but a subgroup of PsA patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema (20%). The RA patient group had a greater degree of MCP synovitis (p<0.0001) and tenosynovitis than PsA patients (p<0.0001). There were no significant differences in either the total number of erosions (p = 0.315) or the presence of periarticular bone oedema (p = 0.105) between the groups. CONCLUSION: Although conventional MRI shows evidence of an enthesitis-associated pathology in the MCP joints in PsA, this is not sufficiently common to be of diagnostic utility.

Heberden's nodes and what Heberden could not see: the pivotal role of ligaments in the pathogenesis of early nodal osteoarthritis and beyond.

Despite its relatively high prevalence, polyarticular nature, limited treatment options and recognized genetic contribution, the study of generalized OA (GOA) has lagged behind that of isolated knee OA. Whilst the pathogenesis of OA has been viewed in relation to either articular cartilage or bone disease, this article offers a viewpoint on why GOA may, in fact, be primarily a disorder of ligaments, and to a lesser extent tendon and joint capsule dysfunction. A relatively fast presentation of GOA, typically in the perimenopausal period, and its recognition on clinical grounds alone makes this type of OA potentially useful for pathogenic studies in OA, in general. The recent high-resolution MRI studies, microanatomical studies and animal models, in addition to established clinical and radiographic data that support this ligament-centric perspective of disease, are reviewed. The earliest structural abnormalities in GOA may be evident in ligaments and the ligament-associated 'enthesis organ', where degenerative changes are evident. Ligaments also influence the expression of joint damage including Heberden's node and joint erosion formation. Joint inflammation in a 'periarthritis' pattern is well recognized in GOA, and histological studies have shown that the ligament and capsule could represent the epicentre of such inflammatory changes. A perspective is also offered on how ligaments could play a pivotal role in OA in general; for example, the loss of joint space in knee OA due to meniscal extrusion could ultimately be related to derangement of the medial collateral ligament to which the meniscus is anchored.

Rituximab use in everyday clinical practice as a first-line biologic therapy for the treatment of DMARD-resistant rheumatoid arthritis.

OBJECTIVES: This study assessed the utility of rituximab for the therapy of RA in a non-academic environment in a group of cases where anti-TNF was either not available or relatively contraindicated. METHODS: Thirty-nine patients with active RA who had failed at least one DMARD received two rituximab infusions 2 weeks apart. Seventeen patients received two 1000 mg doses, and 22 received the 500 mg regimen. The 28-joint disease activity index (DAS28) and European League against Rheumatism (EULAR) response criteria were recorded at baseline, 3, 6, 9 and 12 months. RF and ANA were recorded at baseline and at 6 and 12 months. RESULTS: There was a significant improvement in the DAS28 at all time points, and EULAR response was observed in 29 of 33 patients (87.9%) at 3 months, 25 of 33 patients (75.8%) at 6 months, 22 of 29 patients (75.9%) at 9 months and 23 of 30 patients (76.7) at 12 months. Improvement was also noted in CRP, and both RF and ANA were generally reduced after treatment. Patients who were on the higher regimen of two 1000 mg doses appeared to respond slightly better compared with the lower dose regimen. CONCLUSIONS: Rituximab is well tolerated in everyday clinical practice and may represent a good short-term treatment option where anti-TNF therapy is either unavailable or relatively contraindicated.

Case Report: Spontaneous Hemorrhage of a Rare Renal Tumor in the Native Kidney of a Renal Transplant Recipient.

Renal cancers are some of the most common solid organ malignancies found during follow-up of patients who have undergone renal transplantation (RT). In this case report, we describe a life-threatening spontaneous hemorrhage of a rare subtype of renal cell carcinoma in the native kidney of a 27-year-old man, 4 years after RT. After fluid resuscitation and stabilization, the patient underwent emergent open radical nephrectomy with the final histopathology reporting T1bN0Mx mucinous tubular and spindle cell (MTSC) carcinoma. This case report highlights the need to consider an underlying malignancy in patients who presents with spontaneous hemorrhage of native kidneys after RT.

Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication.

Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia wStri, isolated from Laodelphax striatellus, was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that wStri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. wStri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by wStri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into wStri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia-infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in wStri-infected cells. This study's findings increase the potential for application of wStri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection.IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont, Wolbachia wStri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use of Wolbachia wStri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy.

Donor-Derived Candida dubliniensis Resulting in Perigraft Abscesses in a Liver Transplant Recipient Proven by Whole Genome Sequencing: A Case Report.

BACKGROUND: The transmission of fungi via transplant, although well-known, has not often been molecularly proven. We describe a case of donor-derived candidiasis verified by whole genome sequencing. CASE DESCRIPTION: The multiorgan donor was a 42-year-old woman with subdural hemorrhage. Procurement of the thoracic organs was performed followed by the abdominal organs. Tissue from the left bronchus grew Candida dubliniensis. The liver recipient was a 63-year-old woman with cryptogenic liver cirrhosis. She was noted to have worsening leukocytosis on postoperative day (POD) 9. Computed tomography of the abdomen and pelvis showed multiple rim-enhancing collections around the graft. Percutaneous drainage was performed. Fluid cultures grew C dubliniensis. C dubliniensis isolated from the donor's left bronchus and the liver recipient's abscesses were verified to be related by whole genome sequencing. We postulate that C dubliniensis colonizing the donor's transected trachea could have contaminated the inferior vena cava when the former was left open after explant of the donor's lungs. A portion of the donor's contaminated inferior vena cava was transplanted along with the liver graft, resulting in the infected collections in the recipient. CONCLUSIONS: Our case report highlights the importance of maintaining a sterile field during organ procurement, especially in a multiorgan donor whose organs are explanted in succession.

Incidence and species distribution of candidaemia in Asia: a laboratory-based surveillance study.

The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16-4.53 per 1000 discharges) and countries (range 0.25-2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries (R² = 0.87) and 25 hospitals (R² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio (R² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albicans was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution.