Morphological Distribution and Internal Enhancement Architecture of Contrast‐Enhanced Magnetic Resonance Imaging in the Diagnosis of Non‐Mass‐Like Breast Lesions: A Meta‐Analysis

The aim of this study is to assess the diagnostic performance of contrast‐enhanced magnetic resonance (MR) imaging in patients with non‐mass‐like breast lesions in a meta‐analysis. Literature study was performed on PubMed data base on the diagnostic performance of MR imaging in patients with non‐mass‐like breast lesions. Details of the relevant studies were reviewed and a meta‐analysis was performed to estimate the overall sensitivity and specificity of contrast‐enhanced MR imaging of non‐mass‐like breast lesions. A summary receiver operating characteristic curve (sROC) was developed to explore the threshold effect by ROC space. Spearman correlation coefficient was calculated using Meta‐Disc version 1.4 to analyze the heterogeneity between studies. A total of 858 non‐mass‐like lesions from 15 studies were included in the meta‐analysis (sample size range: 27–131). Pooled weighted estimates of sensitivity and specificity were 50% (95% CI: 46%, 53%) and 80% (95% CI: 77%, 83%), respectively. The heterogeneity among studies was caused by other factors other than threshold effect. The findings were influenced by cancer prevalence (p = 0.0359). Subgroup analyses indicated that the sensitivity and specificity in studies with combined diagnostic criterion was higher than that in studies with single diagnostic criterion. In evaluation of non‐mass‐like breast lesions, contrast‐enhanced MRI has high specificity and relatively lower sensitivity.     

Enhancing Braden pressure ulcer risk assessment in acutely ill adult veterans

This study sought to determine if a parsimonious pressure ulcer (PU) predictive model could be identified specific to acute care to enhance the current PU risk assessment tool (Braden Scale) utilized within veteran facilities. Factors investigated include: diagnosis of gangrene, anemia, diabetes, malnutrition, osteomyelitis, pneumonia/pneumonitis, septicemia, candidiasis, bacterial skin infection, device/implant/graft complications, urinary tract infection, paralysis, senility, respiratory failure, acute renal failure, cerebrovascular accident, or congestive heart failure during hospitalization; patient's age, race, smoking status, history of previous PU, surgery, hours in surgery; length of hospitalization, and intensive care unit days. Retrospective chart review and logistic regression analyses were used to examine Braden scores and other risk factors in 213 acutely ill veterans in North Florida with (n = 100) and without (n = 113) incident PU from January–July 2008. Findings indicate four medical factors (malnutrition, pneumonia/pneumonitis, candidiasis, and surgery) have stronger predictive value (sensitivity 83%, specificity 72%, area under receiver operating characteristic [ROC] curve 0.82) for predicting PUs in acutely ill veterans than Braden Scale total scores alone (sensitivity 65%, specificity 70%, area under ROC curve 0.70). In addition, accounting for four medical factors plus two Braden subscores (activity and friction) demonstrates better overall model performance (sensitivity 80%, specificity 76%, area under ROC curve 0.88).     

Uncertainty of current algorithm for bisphosphonate‐related osteonecrosis of the jaw in population‐based studies: a systematic review

To assess the relevance of previous epidemiologic studies on bisphosphonate‐related osteonecrosis of the jaw (BRONJ), we first conducted a systematic review of large population‐based observational studies and evaluated the validity of claims‐based algorithms for the identification of BRONJ. Studies containing primary observational epidemiologic data regarding bisphosphonate (BP) exposure and outcomes of osteonecrosis of the jaw were systematically reviewed. Using surrogates for identifying potential BRONJ cases from a population‐based hospital registry, validation was performed through medical chart review. Positive predictive value (PPV) was estimated for each diagnostic code and for the overall algorithm utilized. Various strategies to increase PPV were also performed. Seventeen studies were systematically reviewed and presented with variations in study quality as well as inconsistent findings. Moreover, there was a high level of methodological heterogeneity. A total of 1920 patients were identified through the ICD‐10 algorithm with potential BRONJ, although only 109 cases were confirmed, corresponding to an overall PPV of 5.68% (95% confidence interval [CI] 4.68–6.81). Only K10.2 (inflammatory conditions of the jaw) exhibited a relatively high PPV of 26.18%, which increased to 74.47% after confinement to BP users. Other strategies to increase PPV value were not effective. Our findings showed that the overall PPV for BRONJ identification was very low, indicating low validity of the current algorithm and possible overestimation of ONJ occurrence. There is an urgent need to develop more reliable and specific operational definitions for the identification of BRONJ cases in large population databases. © 2016 American Society for Bone and Mineral Research.     

Predictive value of computed tomography in identifying extranodal extension in human papillomavirus‐positive versus human papillomavirus‐negative head and neck cancer

Pathologic extranodal extension (pENE) impacts treatment planning and is an important prognostic indicator for patients with head and neck squamous cell carcinoma (HNSCC). Computed tomography (CT) is a commonly used modality for assessment of radiographic ENE (rENE). To determine the predictive value of CT‐identified rENE in predicting pENE, we performed a systematic review through a search of 4 databases (PubMed, Scopus, Cochrane, and OVID). Meta‐analysis of diagnostic performance based on human papillomavirus (HPV) status was conducted. For HPV‐negative HNSCC, pooled sensitivity, specificity, and accuracy were 60.6%, 93.3%, and 82.6%, respectively. Overall positive predictive value (PPV) was 82.7%. For HPV‐positive HNSCC, pooled sensitivity, specificity, and accuracy were 77.7%, 72.2%, and 63.8%, respectively. Overall PPV was 68.6%. Significant differences were observed in diagnostic performance parameters between the two cohorts. The radiographic characteristics of HPV‐positive and HPV‐negative nodal metastases in HNSCC differ and radiographic evaluation of ENE in HPV‐positive nodes is challenging. Development of refined imaging characteristics of HPV‐positive nodes is needed to improve diagnostic performance.     

Comparative Diagnostic Utility of Low‐Dose Breast‐Specific Gamma Imaging to Current Clinical Standard

To retrospectively compare low‐dose (7–10 mCi) to high‐dose (15–30 mCi) breast‐specific gamma imaging (BSGI) in the detection of breast cancer. A retrospective review of 223 consecutive women who underwent BSGI exam between February 2011 and August 2013 with subsequent pathologic analysis was performed. Women were divided into low‐dose and high‐dose groups. The results of BSGI and pathology were compared, and the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. A subgroup analysis was performed to evaluate specificity using benign follow‐up imaging to establish true‐negative results. There were 223 women who met inclusion criteria with 109 patients with 153 lesions in the low‐dose group and 114 patients with 145 lesions in the high‐dose group. Pathologic correlation demonstrates sensitivities of 97.6% (95% CI = 90.9–99.6%) and 94.6% (95% CI = 84.2–98.6%; p = 0.093), PPVs of 62.1% (95% CI = 53.2–70.3%) and 50.5% (95% CI = 40.6–60.3%, p = 0.089), and NPVs of 90.5% (95% CI = 68.2–98.3%) and 92.5% (95% CI = 78.5–98.0%, p = 0.781) in the low‐dose and high‐dose groups, respectively. Subgroup analysis included 72 patients with 98 lesions in the low‐dose group and 116 patients with 132 lesions in the high‐dose group, with a specificity of 53.7% (95% CI = 39.7–67.1%) and 66.3% (95% CI = 56.2–75.2%%, p = 0.143), respectively. Low‐dose BSGI demonstrated high sensitivity and NPV in the detection of breast cancer comparable to the current standard dose BSGI, with moderate specificity and PPV in a limited subgroup analysis, which was associated with a substantial number of false‐positives.     

Sensitivity and Specificity of Unilateral Edema on T2w‐TSE Sequences in MR‐Mammography Considering 974 Histologically Verified Lesions

Abstract: The objective of this investigation was to determine the diagnostic value of unilateral edema in differentiating benign from malignant breast disease on T2w‐TSE images in MR‐Mammography (MRM). All patients from a 10‐year period undergoing surgery in the same institution after having received MRM in our department were included in this prospective analysis of previous acquired examinations. To eliminate bias caused by prior procedures, all patients having had biopsy, operation, radiation therapy, or chemotherapy before MRM were excluded. T2w‐TSE images were acquired after a dynamic contrast‐enhanced series of T1‐weighted images in a standardized examination protocol (1.5 T). Edema was defined as a high‐signal intensity on T2w‐TSE images and it was categorized as absent, perifocal, or diffuse. Examinations were rated by two experienced observers blinded to all procedures and results following MRM. In cases of disconcordance, the opinion of a third radiologist decided. Statistical testing included Pearson’s Chi‐squared test and Fisher’s exact testing. A total of 1,010 patients with a mean age of 55 years (SD: 11.6 years, range: 16–87 years) with 1,129 histologically verified lesions were included in this investigation. After removing all patients with prior procedures from the patient collective, 974 lesions were left for statistical analysis. Perifocal edema was highly significantly (p < 0.001) associated with malignant disease, leading to a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 33.5%, 93.9%, 89.6, and 57.1%, respectively. Unilateral edema in general showed the following diagnostic parameters: sensitivity 53.0%, specificity 80.5%, PPV 80.9%, and NPV 52.3%. Edema seems to be associated with malignancy in the majority of cases. Especially, specificity and PPV were found to be high. These findings may be helpful in diagnostic decisions on otherwise equivocal cases.     

Predicting tumour location in radical prostatectomy specimens: same‐patient comparisons of 21‐sample versus sextant biopsy

OBJECTIVE

To determine the value of a 21‐sample biopsy protocol in predicting tumour localization in radical prostatectomy (RP) specimens, compared with sextant biopsies.

PATIENTS AND METHODS

In all, 300 consecutive patients underwent 21‐sample prostate biopsies, followed by RP. The protocol consisted of sextant, three midline, six far lateral and six transitional zone biopsies. Tumour locations on biopsies and RP specimens were compared. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) and accuracy were calculated.

RESULTS

There was no difference between sextant and 21‐sample biopsies for sensitivity (38% vs 36%; P = 0.50) and specificity (84% vs 87%; P = 0.46), but the NPV was higher for 21‐sample biopsies (57% vs 68% ; P < 0.001). The PPV was higher in the sextant biopsies (74% vs 59%; P = 0.007). Sextant, transitional zone and far lateral biopsies were re‐grouped in six regions. Compared with 21‐sample biopsies, sensitivity (54%) and PPV (79%) were higher (P < 0.001), while specificity (74%) and NPV (46%) were lower (P = 0.05 and P = 0.001, respectively).

CONCLUSION

A negative biopsy does not confirm the absence of cancer in the corresponding site in the RP specimen in a sextant or 21‐sample biopsy protocol and cannot be used as a prognostic element before RP. A positive biopsy does not always correspond with a tumour in the same zone of the RP specimen. When 21‐sample biopsies are re‐grouped in to six regions, the value of a positive biopsy increases. A positive biopsy corresponds thus to a tumour in the same region, rather than in precisely the same location. The results of this study could help in the biopsy protocol used for making surgical decisions, e.g. preserving the bladder neck or neurovascular bundles.     

Evaluation of contrast‐enhanced digital mammography (CEDM) in the preoperative staging of breast cancer: Large‐scale single‐center experience

One of the most important indications for contrast‐enhanced breast imaging is the presurgical breast cancer (BC) staging. This is a large‐scale single‐center experience which evaluates the role of CEDM in presurgical staging and its impact on surgical planning. The aims of this retrospective study were to define the diagnostic performance of CEDM in the presurgical setting and to identify which types of patients could benefit from having CEDM. We selected 326 patients with BC who underwent CEDM as preoperative staging and had breast cancer‐related surgery at our institution. We analyzed those cases in which CEDM led to additional imaging or biopsy and those in which it changed the type of surgery that was planned according to conventional breast imaging (CI) techniques (digital mammography, tomosynthesis and bilateral handheld ultrasound). CEDM sensitivity in identifying the index lesion and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy in the correct preoperative staging of BC of the whole population and in various subgroups were calculated. CEDM sensitivity for the index lesion was 98.8% (322/326), which led to additional breast imaging in 23.6% (77/326) of patients and additional biopsies in 17.5% (57/326). CEDM changed the type of surgery in 18.4% (60/326). In the preoperative breast cancer staging, CEDM sensitivity, specificity, PPV, NPV, and accuracy produced results of 93%, 98%, 90%, 98%, and 97%, respectively. CEDM performance was better in patients with palpable lesions. CEDM has an excellent diagnostic performance in the presurgical staging of BC. Symptomatic patients with palpable lesions benefitted most from preoperative CEDM, with a statistically significant difference compared with nonpalpable.     

Role of Fusion of Prone FDG‐PET and Magnetic Resonance Imaging of the Breasts in the Evaluation of Breast Cancer

Abstract: The purpose of this study is to report further about the statistically significant results from a prospective study, which suggests that fusion of prone F‐18 Fluoro‐deoxy‐glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) breast scans increases the positive predictive value (PPV) and specificity for patients in whom the MR outcome alone would be nonspecific. Thirty‐six women (mean age, 43 years; range, 24–65 years) with 90 lesions detected on MR consented to undergo a FDG‐PET scan. Two blinded readers evaluated the MR and the computer tomography (CT) attenuation‐corrected prone FDG‐PET scans side‐by‐side, then after the volumes were superimposed (fused). A semiautomatic, landmark‐based program was used to perform nonrigid fusion. Pathology and radiologic follow‐up were used as the reference standard. The sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy (with 95% confidence intervals) for MR alone, FDG‐PET alone, and fused MR and FDG‐PET were calculated. The median lesion size measured from the MR was 2.5 cm (range, 0.5–10 cm). Histologically, 56 lesions were malignant, and 15 were benign. Nineteen lesions were benign after 20–47 months of clinical and radiologic surveillance. The sensitivity of MR alone was 95%, FDG‐PET alone was 57%, and fusion was 83%. The increase in PPV from 77% in MR alone to 98% when fused and the increase in specificity from 53% to 97% were statistically significant (p < 0.05). The false‐negative rate on FDG‐PET alone was 26.7%, and after fusion this number was reduced to 9%. FDG‐PET and MR fusions were helpful in selecting which lesion to biopsy, especially in women with multiple suspicious MR breast lesions.     

Diagnostic Performance of MR‐guided Vacuum‐Assisted Breast Biopsy: 8 Years of Experience

Breast magnetic resonance imaging (MRI) has demonstrated increased sensitivity over conventional imaging in identifying and characterizing in situ and invasive, multifocal, and multicentric disease. A histologic diagnosis is required for any enhancing lesion displaying suspicious features, especially in the presence of lower and often variable reported specificity values. Breast MRI findings occult on mammography and ultrasound should undergo an MR‐guided biopsy. We retrospectively evaluate our 8 years’ experience with this procedure. Our study included 259 lesions in 255 consecutive patients referred for MR‐guided breast biopsy. MRI screening of women at a high risk for developing breast cancer accounted for 84 lesions, 54 lesions were detected on MRI staging for multifocal and multicentric disease, and 115 were incidental findings or lesions that presented diagnosis related issues on conventional imaging. Six procedures were cancelled due to lack of visualization. MR‐guided breast biopsy was performed for 100 mass and 153 nonmass enhancements. Pathology results were classified into benign (113 lesions), high risk (47 lesions), and malignant (40 ductal carcinoma in situ, 38 invasive ductal carcinoma, 15 invasive lobular carcinoma). Subsequent surgery for high risk and malignant findings revealed an underestimation rate of 34% (16/47) for high risk lesions and of 7.5% for ductal carcinoma in situ (3/40). The overall positive predictive value (PPV) was calculated at 43.1% (33.3% for high‐risk women, 70.3% for cancer staging, and 37.4% for incidental/undetermined lesions). The PPV was higher for mass (57%) versus nonmass enhancements (34%). MR‐guided breast biopsy proved to be a reliable procedure for the diagnosis and management of occult breast MRI findings, or lesions that preclude biopsy under conventional guidance. The PPV displayed significant variation between patient subgroups, correlating higher values with a higher associated breast cancer prevalence.     

Monitoring of CMV‐specific cell‐mediated immunity with a commercial ELISA‐based interferon‐γ release assay in kidney transplant recipients treated with antithymocyte globulin

Monitoring for cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMV‐CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA‐based interferon (IFN)‐γ release assay (QTF‐CMV) from posttransplant months 2‐5 (362 points) in 120 CMV‐seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92 days). Forty‐seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF‐CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF‐CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV‐CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value [PPV]: 64.1%; negative predictive value [NPV]: 50.0%), with no differences in 1‐year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P = .244). Specificity and PPV to predict protective CMV‐CMI improved by elevating the IFN‐γ cutoff value to 1.13 IU/mL (65.7% and 71.4%) and 7.0 IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF‐CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG‐treated CMV‐seropositive KT recipients. This performance is slightly improved by modifying the IFN‐γ positivity threshold.     

Evaluation of validity of the new diabetic foot ulcer assessment scale in Indonesia

We developed a new assessment tool for diabetic foot ulcers because no such tool specifically for diabetic foot ulcer exists. The diabetic foot ulcer assessment scale (DFUAS) has 11 domain items. The minimum and maximum scores on this scale are 0 and 98, respectively; higher scores indicate more severe wounds. The aim of this study was to evaluate the concurrent validity, construct validity and predictive validity of DFUAS in Indonesia. A prospective cohort study was conducted on patients with diabetic foot ulcer at Kitamura wound clinic in Indonesia. A total of 62 patients with 70 diabetic foot ulcers were assessed with DFUAS tool, Bates‐Jensen wound assessment tool (BWAT), and pressure ulcer scale for healing (PUSH). Concurrent validity was determined by correlation of the DFUAS total score with the external criterion (BWAT, PUSH, and wound surface area). A comparison between the total DFUAS score and chronic wound status was made to determine construct validity. We also analyzed 41 wounds that were followed for 4 weeks to evaluate predictive validity. The correlation coefficient total scores of the DFUAS against the BWAT, PUSH, and wound surface area were 0.92, 0.87, and 0.82, respectively. The comparison of the total DFUAS score with chronic wound status was p < 0.001. The predictive validity test indicated that a DFUAS cutoff score of 12 produced the best balance of sensitivity, specificity, positive predictive value, and negative predictive value (89%, 71%, 86%, and 77%, respectively). In conclusion, the newly developed DFUAS is a valid tool for assessing diabetic foot ulcers.     

MRI for detecting silicone breast implant rupture: meta-analysis and implications

The objective of this study was to assess the accuracy of magnetic resonance imaging (MRI) in detecting silicone breast implant rupture, and to explore implications of the use of MRI for screening and estimating the prevalence of rupture among asymptomatic women. The study consisted of a meta-analysis of published studies with the calculation of sensitivity and specificity as independent parameters, the summary receiver operating characteristic (ROC) curve, and other clinically important values such as positive predictive value (PPV) and negative predictive value. Participants included women with breast implants who underwent both MRI and subsequent implant removal. Eighteen studies, performed primarily in academic settings, with approximately 1,039 women and 2,036 implants met entry criteria. Most studies involved women with symptomatic implants. Assuming that sensitivity and specificity were independent parameters, the summary sensitivity was 78% (95% confidence interval [CI], 71-83) and the summary specificity was 91% (95% CI, 86-94). Using ROC meta-analysis methodology, the odds ratio describing the overall accuracy of the test was 40.1 (range, 18.8-85.4). There was substantial heterogeneity across studies. Studies using breast coils, those with convenience samples, larger studies, and studies of lower report quality tended to report higher levels of accuracy. The quality of study reports was generally poor. Among symptomatic women, PPV was fairly high. Among lower prevalence populations, PPV appeared to be insufficient to warrant use as a screening tool. MRI is moderately accurate in detecting silicone breast implant rupture. However, MRI should remain a confirmatory diagnostic test and should not be used to screen asymptomatic women.     

Apolipoprotein A‐Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: diagnostic performance and assessment of its prognostic value – a multi‐centre cohort study

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) is a serious complication after kidney transplantation. FSGS relapse is suspected by a sudden increase in proteinuria but there is not an accurate noninvasive diagnostic tool to confirm this entity or to detect patients at risk. We aimed to validate the diagnostic performance of ApoA‐Ib to detect FSGS relapses by measuring urinary ApoA‐Ib in a retrospective cohort of 61 kidney transplanted patients (37 FSGS and 24 non‐FSGS). In addition, to assess the ApoA‐Ib predictive ability, ApoA‐Ib was measured periodically in a prospective cohort of 13 idiopathic FSGS patients who were followed during 1 year after transplantation. ApoA‐Ib had a sensitivity of 93.3% and a specificity of 90.9% to diagnose FSGS relapses, with a high negative predictive value (95.2%), confirming our previous results. In the prospective cohort, ApoA‐Ib predated the recurrence in four of five episodes observed. In the nonrelapsing group (n = 9), ApoA‐Ib was negative in 37 of 38 samples. ApoA‐Ib has the potential to be a good diagnostic biomarker of FSGS relapses, providing a confident criterion to exclude false positives even in the presence of high proteinuria. It has also the potential to detect patients at risk of relapse, even before transplantation.     

The value of clinical characteristics and breast-imaging studies in predicting a histopathologic diagnosis of cancer or high-risk lesion in patients with spontaneous nipple discharge

BACKGROUND: The purpose of this study was to determine the utility of breast-imaging studies in identifying cancer and high-risk lesions among patients with spontaneous, single-duct, nipple discharge (SSND). METHODS: The medical records of 168 cases with SSND treated with duct excision between June 1998 and May 2004 were reviewed. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mammogram, ultrasound, and ductogram in predicting high-risk lesions and cancer were calculated. RESULTS: The sensitivity of mammography was 10%, the specificity 94%, the NPV 88%, and the PPV 18%. Ultrasonography had a sensitivity of 36%, specificity of 68%, PPV of 14%, and NPV of 89%. Ductography had a sensitivity of 75%, specificity of 49%, and NPV and PPV of 93% and 18%, respectively. CONCLUSIONS: Conventional imaging studies do not accurately identify cancer or high-risk lesions in patients with SSND.All patients with SSND should be offered duct excision.     

Concordance of Shape Risk Scale,a new pressure ulcer risk tool,with Braden Scale

The occurrence of pressure ulcers was examined in a cross‐sectional study in 23 health care facilities and in home care involving 548 patients. The screening of pressure ulcer risk was assessed simultaneously using the Braden Scale and the new Shape Risk Scale (SRS), and the results were compared. The overall prevalence of pressure ulcers in the study population was 15·5% (85/548). The Braden Scale was performed as described in the literature. The direct concordance of the Braden and SRS scales was 46%. In more than 90% of cases, the SRS classified patients as well as or better than the Braden Scale. The SRS allocates patients significantly different from the Braden Scale into the risk categories, especially the difference is significant between the low and medium‐risk categories. The greatest advantage of SRS to Braden Scale is that it correctly identifies patients with low risk of pressure ulcers. It is interesting that the two risk scores, taking into consideration the basically different pathophysiological factors, can still give rather similar results. The users considered that both scales are easy to use.     

Discovery and validation of a novel blood‐based molecular biomarker of rejection following liver transplantation

Noninvasive biomarker profiles of acute rejection (AR) could affect the management of liver transplant (LT) recipients. Peripheral blood was collected following LT for discovery (Northwestern University [NU]) and validation (National Institute of Allergy and Infectious Diseases Clinical Trials in Organ Transplantation [CTOT]‐14 study). Blood gene profiling was paired with biopsies showing AR or ADNR (acute dysfunction no rejection) as well as stable graft function samples (Transplant eXcellent—TX). CTOT‐14 subjects had serial collections prior to AR, ADNR, TX, and after AR treatment. NU cohort gene expression (46 AR, 45 TX) was analyzed using random forest models to generate a classifier training set (36 gene probe) distinguishing AR vs TX (area under the curve 0.92). The algorithm and threshold were locked and tested on the CTOT‐14 validation cohort (14 AR, 50 TX), yielding an accuracy of 0.77, sensitivity 0.57, specificity 0.82, positive predictive value (PPV) 0.47, and negative predictive value (NPV) 0.87 for AR vs TX. The probability score line slopes were positive preceding AR, and negative preceding TX and non‐AR (TX + ADNR) (P ≤ .001) and following AR treatment. In conclusion, we have developed a blood biomarker diagnostic for AR that can be detected prior to AR‐associated graft injury as well a normal graft function (non‐AR). Further studies are needed to evaluate its utility in precision‐guided immunosuppression optimization following LT.     

A meta‐analysis of interleukin‐6 as a valid and accurate index in diagnosing early neonatal sepsis

We aimed to systematically assess the overall value of interleukin 6 (IL‐6) in diagnosing neonates with sepsis. A systematic literature search was conducted using the following electronic databases: PubMed, Embase, and Cochrane, to identify eligible studies through the index words updated till November 2018. Cross‐sectional studies, as well as prospective cohort studies, were included in the above‐mentioned group of eligible studies. We also searched the literature sources that had a link to the present study, which were further assessed by heterogeneity through the use of a proper‐effects model to calculate pooled weighted specificity, sensitivity, and diagnostic odds ratio (DOR). We also conducted summary receiver operating characteristic (SROC) analyses for neonatal sepsis. In the present meta‐analysis, there were 31 studies exploring IL‐6 for the diagnostic accuracy of neonatal sepsis. The global specificity and sensitivity of IL‐6 for neonatal sepsis were as follows: 88% (95% confidence interval [CI]: 83%‐92%) and 82% (95% CI: 77%‐86%), respectively. The global positive and negative likelihood ratio of IL‐6 in diagnosing neonatal sepsis were 7.03 (95% CI: 4.81‐10.26) and 0.20 (95% CI: 0.15‐0.26), respectively. The global DOR was 29.54 (95%CI: 18.56‐47.04) of IL‐6. In addition, the area under the SROC was high for IL‐6 (AUC = 0.92; 95% CI: 0.89‐0.94). In this study, we performed a systematic review and meta‐analysis to assess the diagnostic accuracy studies of IL‐6 in diagnosing neonatal sepsis. Our results suggested that IL‐6 is a valid and accurate index in diagnosing early neonatal sepsis, but it still needs to be combined with other laboratory tests and specific clinical manifestations.     

甲状腺结节超声引导下粗针穿刺组织学活检的有效性研究

目的研究甲状腺结节超声引导下粗针穿刺(US－CNB)组织学活检的有效性,探讨其对甲状腺结节的诊断价值。 方法回顾性分析2009年6月至2016年6月行术前US－CNB的2 051例患者的2 286个结节的病理诊断,将其中在本院行手术切除的530个甲状腺结节纳入本研究。以术后组织病理学为金标准,采用SPSS 19.0统计软件分析处理数据,分析US－CNB病理诊断的敏感度、特异度、阳性预测值、阴性预测值、准确度,并用ROC曲线对比粗针穿刺活检病理结果及手术病理结果。 结果US－CNB的2 286个甲状腺结节中仅2例取材不成功,2 284个(99.9%)结节取材切片成功,得到组织病理诊断;530个术后结节的US－CNB的诊断敏感度、特异度、阳性预测值、阴性预测值、准确度分别99.8%、86.5%、98.6%、97.8%和98.5%。 结论由于US－CNB对甲状腺结节有很高的取材成功率及病理诊断准确率,从而对甲状腺结节有很高的术前诊断价值。     

Application of 11C‐acetate positron‐emission tomography (PET) imaging in prostate cancer: systematic review and meta‐analysis of the literature

• To review the literature on the application of ¹¹C‐acetate positron‐emission tomography (PET) imaging in prostate cancer.

• We systematically reviewed the available literature and presented the results in meta‐analysis format.
• PubMed, SCOPUS, ISI web of knowledge, Science Direct, Springer, and Google Scholar were searched with ‘Acetate AND PET AND Prostate’ as keywords.
• All studies that evaluated accuracy of ¹¹C‐acetate imaging in primary or recurrent prostate cancer were included, if enough data could be extracted for calculation of sensitivity and/or specificity.

• In all, 23 studies were included in the study. For evaluation of primary tumour, pooled sensitivity was 75.1 (69.8–79.8)% and specificity was 75.8 (72.4–78.9)%.
• For detection of recurrence, sensitivity was 64 (59–69)% and specificity was 93 (83–98)%. Sensitivity for recurrence detection was higher in post‐surgical vs post‐radiotherapy patients and in patients with PSA at relapse of >1 ng/mL.
• Studies using PET/computed tomography vs PET also showed higher sensitivity for detection of recurrence.

• Imaging with ¹¹C‐acetate PET can be useful in patients with prostate cancer. This is especially true for evaluation of patients at PSA relapse, although the sensitivity is overall low.
• For primary tumour evaluation (localisation of tumour in the prostate and differentiation of malignant from benign lesions), ¹¹C‐acetate is of limited value due to low sensitivity and specificity.
• Due to the poor quality of the included studies, the results should be interpreted with caution and further high‐quality studies are needed.