腺苷脱氨酶在结核性胸膜炎和恶性胸腔积液的对比临床分析

目的：探究腺苷脱氨酶在结核性胸腔积液和恶性胸腔积液中的含量规律。方法：回顾分析自2010年3月至2012年5月于本院胸心外科住院的胸腔积液患者,对穿刺获得的胸腔积液,用比色法测定胸腔积液中腺苷脱氨酶的水平。测量血中腺苷脱氨酶的水平进行对比。结果：结核性胸膜炎组患者胸腔积液ADA测定值为89．67±47．85IU／L,癌性胸腔积液组水平为24．56±11．491U／L,胸腔积液ADA水平在结核性胸膜炎与癌性胸腔积液组之间存在显著性差异（P〈0．05）;以ADA〉45IU／L诊断结核性胸膜炎：则敏感性为（48／51）94．1,特异性为（48／52）88．9％,以ADA〈45IU／L一诊断恶性胸腔积水：则敏感性（（51／55）89．4％,特异性为（51／54）94．4％;结核性胸膜炎中胸腔积液ADA／血清中ADA比值为2．25±0．72,癌性胸腔积液组水平0．43＋0．1,结核性胸膜炎与癌性胸腔积液组之间存在显著性差异（P〈0．05）;以胸腔积液ADA／血清中ADA比值〉1．0为界诊断结核性胸膜炎：则敏感性为（46／51）90．1,特异性为（45／55）81．8．％,以胸腔积液ADA／血清中ADA比值〈1．0诊断恶性胸腔积水：则敏感性（47／57）82．4％,特异性为（47／53）88．7％。结论：腺苷脱氨酶在结核性胸膜炎和恶性胸腔积液中的含量有明显差异。     

Adenosine deaminase activity is a sensitive marker for the diagnosis of tuberculous pleuritis in patients with very low CD4 counts

Background

Adenosine Deaminase Activity (ADA) is a commonly used marker for the diagnosis of tuberculous pleural effusion. There has been concern about its usefulness in immunocompromised patients, especially HIV positive patients with very low CD4 counts. The objective of this study was to evaluate the sensitivity of ADA in pleural fluid in patients with low CD4 counts.

Materials and Methods

This was a retrospective case control study. Medical files of patients with tuberculous pleuritis and non-tuberculous pleuritis were reviewed. Clinical characteristics, CD4 cell counts in blood and biochemical markers in pleural fluid, including ADA were recorded.

Results

One ninety seven tuberculous pleuritis and 40 non- tuberculous pleuritis patients were evaluated. Using the cut-off value of 30 U/L, the overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ADA was 94%, 95%, 19, and 0.06 respectively. The mean CD4 cell counts among TB pleuritis patients was 29 and 153 cells/microL in patients with CD4 <50 cells/microL and >50 cells/microL, (p<0.05) respectively. The corresponding mean ADA values for these patients were 76 U/L and 72 U/L respectively (p>0.5). There was no correlation between ADA values and CD4 cell counts (r = −0.120, p = 0.369).

Conclusion

ADA analysis is a sensitive marker of tuberculous pleuritis even in HIV patients with very low CD4 counts in a high TB endemic region. The ADA assay is inexpensive, rapid, and simple to perform and is of great value for the immediate diagnosis of tuberculous pleuritis while waiting for culture result and this has a positive impact on patient outcome.     

Pleural Fluid Adenosine Deaminase (Pfada) in the Diagnosis of Tuberculous Effusions in a Low Incidence Population

IntroductionPrevious studies have assessed the diagnostic ability of pleural fluid adenosine deaminase (pfADA) in detecting tuberculous pleural effusions, with good specificity and sensitivity reported. However, in North Western Europe pfADA is not routinely used in the investigation of a patient with an undiagnosed pleural effusion, mainly due to a lack of evidence as to its utility in populations with low mycobacterium tuberculosis (mTB) incidence.MethodsPatients presenting with an undiagnosed pleural effusion to a tertiary pleural centre in South-West England over a 3 year period, were prospectively recruited to a pleural biomarker study. Pleural fluid from consecutive patients with robust 12-month follow up data and confirmed diagnosis were sent for pfADA analysis.ResultsOf 338 patients enrolled, 7 had confirmed tuberculous pleural effusion (2%). All mTB effusions were lymphocyte predominant with a median pfADA of 72.0 IU/L (range- 26.7 to 91.5) compared to a population median of 12.0 IU/L (range- 0.3 to 568.4). The optimal pfADA cut off was 35 IU/L, which had a negative predictive value (NPV) of 99.7% (95% CI; 98.2-99.9%) for the exclusion of mTB, and sensitivity of 85.7% (95% CI; 42.2-97.6%) with an area under the curve of 0.88 (95% CI; 0.732–1.000).DiscussionThis is the first study examining the diagnostic utility of pfADA in a low mTB incidence area. The chance of an effusion with a pfADA under 35 IU/L being of tuberculous aetiology was negligible. A pfADA of over 35 IU/L in lymphocyte-predominant pleural fluid gives a strong suspicion of mTB.     

细胞因子IFN-γ,IL-2,TNF-α和ADA对结核性和恶性胸腔积液鉴别诊断的价值

目的：探讨细胞因子γ-干扰素（IFN-γ）、白介素-2（IL-2）、肿瘤坏死因子-α（TNF-α）和腺苷脱氨酶（ADA）对结核性和恶性胸腔积液的鉴别诊断的价值。方法：以2012年9月至2013年3月期间在青岛大学医学院附属医院呼吸科及青岛胸科医院未经治疗的胸腔积液患者为研究对象,其中恶性胸腔积液患者46例,结核性胸腔积液患者42例。采用双抗体夹心酶联免疫吸附测定法（ELISA）分别检测结核性和恶性胸腔积液患者中IFN-γ、IL-2、TNF-α及ADA的表达情况。并应用ROC曲线分析两组患者胸腔积液中IFN-γ、IL-2、TNF-α及ADA的表达差异及意义。结果：结核性胸腔积液组IFN-γ、IL-2、TNF-α及ADA的表达明显高于恶性胸腔积液组,差异有统计学意义（t=8.118、8.126、8.066、7.221;P=0.000、0.000、0.000、0.000,P〈0.001）;ROC曲线分析结果显示胸腔积液中IFN-γ、IL-2、TNF-α及ADA的诊断临界值为201.45 pg/mL、41.91 pg/mL、21.55 pg/mL、33.78 U/L;诊断敏感度分别为91.3%、93.5%、91.2%、89.1%;特异度分别为91.0%、92.1%、89.9%、90.1%。结论：胸腔积液中IFN-γ、IL-2、TNF-α及ADA的表达对结核性和恶性胸腔积液诊断与鉴别诊断具有重要参考价值。     

Prevalence,Hemodynamics, and Cytokine Profile of Effusive-Constrictive Pericarditis in Patients with Tuberculous Pericardial Effusion

Background

Effusive constrictive pericarditis (ECP) is visceral constriction in conjunction with compressive pericardial effusion. The prevalence of proven tuberculous ECP is unknown. Whilst ECP is distinguished from effusive disease on hemodynamic grounds, it is unknown whether effusive-constrictive physiology has a distinct cytokine profile. We conducted a prospective study of prevalence and cytokine profile of effusive-constrictive disease in patients with tuberculous pericardial effusion.

Methods

From July 2006 through July 2009, the prevalence of ECP and serum and pericardial levels of inflammatory cytokines were determined in adults with tuberculous pericardial effusion. The diagnosis of ECP was made by combined pericardiocentesis and cardiac catheterization.

Results

Of 91 patients evaluated, 68 had tuberculous pericarditis. The 36/68 patients (52.9%; 95% confidence interval [CI]: 41.2-65.4) with ECP were younger (29 versus 37 years, P=0.02), had a higher pre-pericardiocentesis right atrial pressure (17.0 versus 10.0 mmHg, P<0.0001), serum concentration of interleukin-10 (IL-10) (38.5 versus 0.2 pg/ml, P<0.001) and transforming growth factor-beta (121.5 versus 29.1 pg/ml, P=0.02), pericardial concentration of IL-10 (84.7 versus 20.4 pg/ml, P=0.006) and interferon-gamma (2,568.0 versus 906.6 pg/ml, P=0.03) than effusive non-constrictive cases. In multivariable regression analysis, right atrial pressure > 15 mmHg (odds ratio [OR] = 48, 95%CI: 8.7-265; P<0.0001) and IL-10 > 200 pg/ml (OR=10, 95%CI: 1.1, 93; P=0.04) were independently associated with ECP.

Conclusion

Effusive-constrictive disease occurs in half of cases of tuberculous pericardial effusion, and is characterized by greater elevation in the pre-pericardiocentesis right atrial pressure and pericardial and serum IL-10 levels compared to patients with effusive non-constrictive tuberculous pericarditis.     

肺癌性胸腔积液中生存素基因检测的诊断意义探讨

目的：生存素基因（survivin）是一种新近发现的抗凋亡基因,在肿瘤组织中呈现表达。本文旨在探讨和比较肺癌性胸腔积液和结核性胸腔积液中生存素基因的表达情况,以及其联合细胞学检查对判断肺癌性胸腔积液的敏感度。方法：应用逆转录酶-聚合酶链反应法（RT-PCR）检测2007年06月～2008年03月42例肺癌患者癌性胸腔积液标本,及同时期28例结核性胸腔积液标本的生存素mRNA表达情况,并联合细胞学检查结果进行对比分析。结果：42例肺癌患者胸腔积液标本中生存素mRNA的阳性率为52138％（22／42）;癌细胞的检出率为30．95％（13／42）;生存素mRNA检测联合细胞学检查诊断肺癌的敏感性为61．90％（26／42）,显著高于单独胸腔积液细胞学检测的敏感性（P〈0．001）。28例结核性胸腔积液标本的生存素mRNA阳性率为7．14％（2／28）,显著低于肺癌患者胸腔积液标本生存素mRNA的阳性率（P〈0．001）。结论：运用RT—PCR方法检测胸腔积液中生存素mRNA的表达在判断肺癌性胸腔积液中具有一定的敏感性和特异性,可能作为肺癌辅助诊断的一个新检测指标。     

Combined carcinoembryonic antigen and cytopathologic examination in ascites

OBJECTIVE: To investigate use of the combined carcinoembryonic antigen (CEA) test and cytopathologic examination to improve the diagnosis of neoplastic vs. nonneoplastic ascites. STUDY DESIGN: The tests were performed prospectively on 130 patients with ascites whose effusions were submitted for cytologic examination. RESULTS: Sixty-seven patients had epithelial tumors, and the cytologic examination was positive in 39 (58.2%). The CEA level was > or = 11.0 ng/mL in 36 patients (53.73%). CEA was helpful in the diagnosis in 18 cases, increasing to 57 (85.07%) the number of positive diagnoses. Eight samples of nonepithelial tumors had low levels of CEA. In 55 patients with nonneoplasic ascites the cytopathologic examination was negative, but the CEA assay was > 11.0 ng/mL in 3 patients. CONCLUSION: The cytopathologic examination should be performed in all cases, and the CEA assay should be done in suspected cases of epithelial neoplasia in which the cytologic examination was negative, there was uncertainty about the histologic type of neoplasia, or a diagnosis of nonepithelial neoplasia was made. When ascitic leukocytosis or hepatic failure is present, one should be cautious in interpreting the CEA assay because false positivity can occur.     

血清和胸水中CA125在结核性和癌性胸水中的表达及临床意义

目的:探讨血清和胸水中CA125在结核性和癌性胸水中的表达及鉴别诊断意义。方法:抽选我院确诊的结核性胸水病人85例(结核组)和癌性胸水病人71例(癌症组),检测两组患者血清和胸水中CA125表达,并以胸水/血清中CA125比值10(p-CA125/s-CA12510)为临界值,观察其对癌性胸水的鉴别特异度、灵敏度及准确性。结果:癌症组胸水中CA125表达及p-CA125/s-CA125比值均显著高于结核组(P0.05);但血清中两组CA125表达比较差异无显著性(P0.05);两组胸水中,以35U/ml为临界值,两组患者阳性率92.9%(79/85)、100%(71/71)比较差异无显著性(X2=7.0718,P=0.0078)。癌症组中p-CA125/sCA125比值10的比率(84.5%VS 17.6%)明显高于结核组(X2=66.6244,P=0.0000);并以其为诊断癌性胸水的临界值,鉴别诊断特异度、灵敏度及准确性分别为82.3%、84.5%、83.3%。结论:血清和胸水中CA125表达对于鉴别结核性或者是癌性胸水的临床意义不大,但是p-CA125/s-CA125比值对于鉴别结核性和癌性胸水具有一定临床价值。     

Cell origins and diagnostic accuracy of interleukin 27 in pleural effusions

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+) T cells, CD8(+) T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.     

Accuracy of liquid-based Pap tests: comparison of concurrent liquid-based tests and cervical biopsies on 782 women with previously abnormal Pap smears

OBJECTIVE: To evaluate the diagnostic performance of a liquid-based Pap test, the ThinPrep Pap test (TP) (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), by comparing concurrent TP and cervical biopsy results on 782 patients who were referred for colposcopy because of previously abnormal conventional Pap smears (CPs). STUDY DESIGN: The ability of TP diagnoses of atypical cells of undetermined significance (ASC-US) and squamous intraepithelial lesions (SILs) to predict biopsy diagnoses of cervical intraepithelial neoplasia (CIN) was analyzed using chi2 and McNemar tests. RESULTS: The rate of agreement between diagnoses of SIL by TP and CIN by biopsy was 74.7%. ASC-US accounted for 16.0% of TP diagnoses. ASC-US had biopsy diagnoses of CIN 1 in 60% and CIN 2/3 in 12.8% of cases. For TP diagnosis of low grade SIL, biopsy diagnoses of CIN 2/3 were found in 13.5% of cases. For TP diagnoses of ASC-US and higher, the proportions of TP and cervical biopsies in comparable diagnostic categories were statistically significant (p < 0.001), with TP having sensitivity of 89.4% and positive predictive value of 89.7% for the detection of CIN. The false positive rate for TP was 8.1%, but rescreening confirmed the presence of abnormal cells in 51 of 63 (81.0%) cases of ASC-US or higher having negative biopsies. TP had a false negative rate of 8.3% and negative predictive value of 61.3%. Rescreening showed that most (77.6%) of the false negative TP specimens failed to have abnormal cells on the slides. CONCLUSION: For patients having previously detected cervical abnormalities by CP, concurrent TP demonstrated the following: (1) that it has high diagnostic accuracy for SIL, (2) that ASC-US was diagnostically equivalent to LSIL, and (3) that false negative TP for SIL can be attributed primarily to sampling rather than cytotechnologists' screening errors.     

Diagnosing Kikuchi disease on fine needle aspiration biopsy: a retrospective study of 44 cases diagnosed by cytology and 8 by histopathology.

OBJECTIVE: To study the accuracy of fine needle aspiration (FNA) diagnosis of Kikuchi lymphadenitis (KL). STUDY DESIGN: Retrospective review of all cases of FNA biopsy of lymph nodes in which KL was diagnosed or suggested. False positive cases were studied. Cases of KL diagnosed by histopathology were examined for the false negative rate of FNA diagnosis. RESULTS: Forty-four cases of KL diagnosed or suggested by FNA were found. Five of eight cases were confirmed on lymph node excision. The false positive rate was 37.5%. One case was nonspecific reactive changes. Two cases were proven to be tuberculous lymphadenitis by culture. Eight cases of KL diagnosed by lymph node excisional biopsy had prior FNA. Four were diagnosed as or suspected to be KL. The false negative rate was 50%. CONCLUSION: The overall accuracy of FNA diagnosis of KL was 56.25%. Detailed study offalse positive cases and knowledge of other conditions suggested that overreliance on certain cytologic features and the morphologic erlap between KL and tuberculous lymphadenitis could have been the reasons for the inaccuracies.     

Fine needle aspiration cytology in the management of male breast masses. Nineteen years of experience.

OBJECTIVE: To determine the utility and accuracy of fine needle aspiration cytology (FNAC) as well as its sensitivity, specificity and predictive value in the diagnosis of male breast masses. STUDY DESIGN: Data on male breast FNAC done between 1978 and 1997 were retrieved from the records of the cytopathology laboratory. FNAC diagnoses were categorized as positive, negative, inconclusive or unsatisfactory. Cytohistologic correlation was done with data from histopathology records. Sensitivity, specificity, diagnostic accuracy and predictive values of FNAC were calculated using standard statistical methods. RESULTS: Five hundred seven of 13,175 patients undergoing breast FNAC were males. Of them, 393/507 had satisfactory aspirates. Of these, 70 were positive (13.8%), 295 were negative (58%), and 29 were inconclusive (5.7%). A total of 114 FNACs (22.5%) were unsatisfactory. Histopathology was available in 97/507 cases. There were no false positive or false negative diagnoses. FNAC had a sensitivity, specificity and diagnostic accuracy of 100% for male breast lesions. CONCLUSION: This large study shows that FNAC is a very accurate tool for diagnosis of male breast lesions. It is highly sensitive and specific, with good cytohistologic correlation. FNAC should therefore be an integral part of the primary assessment of breast lumps in males.     

Correlation of endoscopic cytology and histology in oesophageal cancer: results in Porto Alegre,RS—Brazil

A retrospective study of oesophageal cytopathology at the Hospital de Clínicas de Porto Alegre (HCPA), RS, Brazil, from 1989 to 1992 was made to assess the sensitivity, specificity, predictive values and accuracy of endoscopic cytology and biopsy; and study the correlation between cytopathological and histopathological diagnosis. Specimens from 94 patients were available for review. The final diagnosis was based on surgical pathology and follow up. The 81 patients with cancer of the oesophagus had the following sex distribution: 64 males and 17 females (a 3.7–1 ratio). No tumour was found in 13 patients. The following conclusions were made: (i) there is excellent correlation between cytology and histology in oesophageal lesions sampled by endoscopy; (ii) a correct positive cytologic report was obtained in 77 (95%) of the 81 proven oesophageal cancers; a false-negative or unsatisfactory result was given in four patients. A false-positive diagnosis of cancer was not made. There were 13 true-negative reports. These findings result in a sensitivity of 95% with 95% confidence intervals (CI) of 90.26–99.74%; a specificity of 100% (CI of 98.5–100%); a positive predictive value of 100% (CI of 99.3–100%); a negative predictive value of 76% (CI of 55.7–96.3%); (iii) a correct positive histological report was obtained in 67 (83%) of the 81 proven oesophageal cancers; a false-negative or unsatisfactory result was given in 14 patients. A false-positive diagnosis of cancer was not made. There were 13 true-negative reports. These findings result in a sensitivity of 83% with 95% CI of 74.82–91.18%; a specificity of 100% (CI of 98.5–100%); a positive predictive value of 100% (CI of 99.25–100%); a negative predictive value of 48% (CI of 29.16–64.84%); (iv) of 81 patients with proven cancer, in 79 (98%) at least one of the methods was positive. In only two patients with cancer were both methods negative. These findings result in a combined sensitivity of 98% (CI of 94.92–100%); a specificity of 100% (CI of 98.5–100%); a positive predictive value of 100% (CI of 99.31–100%); and a negative predictive value of 87% (CI of 70–100%). Our series confirms the value of the combined use of cytology and biopsy for the investigation of oesophageal lesions. However, it should be remembered that even with the combined use of cytology and biopsy there are some tumours that will be negative by both procedures: we had only two such cases, confirming the rarity of such an event.     

The effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat

Inherited deficiency of the enzyme adenosine deaminase (ADA) has been found in a significant proportion of patients with severe combined immunodeficiency disease and inherited defect generally characterized by a deficiency of both B and T cells. Two questions are central to understanding the pathophysiology of this disease: (1) at what stage or stages in lymphocyte development are the effects of the enzyme deficiency manifested; (2) what are the biochemical mechanisms responsible for the selective pathogenicity of the lymphoid system. We have examined the stage or stages of rat T-cell development in vivo which are affected by an induced adenosine deaminase deficiency using the ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2'-deoxycoformycin (DCF). In normal rats given daily administration of an ADA inhibitor, cortical thymocytes were markedly depleted; peripheral lymphocytes and pluripotent hemopoietic stem cells (CFU-S) all were relatively unaffected. Since a deficiency of ADA affects lymphocyte development, the regeneration of cortical and medullary thymocytes and their precursors after sublethal irradiation was used as a model of lymphoid development. By Day 5 after irradiation the thymus was reduced to 0.10-0.5% of its normal size; whereas at Days 9 and 14 the thymus was 20-40% and 60-80% regenerated, respectively. When irradiated rats were given daily parenteral injections of the ADA inhibitor plus adenosine or deoxyadenosine, thymus regeneration at Days 9 and 14 was markedly inhibited, whereas the regeneration of thymocyte precursors was essentially unaffected. Thymus regeneration was at least 40-fold lower than in rats given adenosine or deoxyadenosine alone. Virtually identical results were obtained with both ADA inhibitors, EHNA and DCF. The majority of thymocytes present at Day 9 and at Day 14 in inhibitor-treated rats had the characteristics of subcapsular cortical thymocytes which are probably the most ancestral of the thymocytes. Thus, an induced ADA deficiency blocked the proliferation and differentiation of subcapsular cortical thymocytes which are the precursors of cortical and medullary thymocytes.     

地塞米松联合尿激酶治疗结核性胸膜炎的临床效果分析

目的:探讨地塞米松联合尿激酶对结核性胸膜炎的临床效果。方法:选择2013年8月到2016年5月在我院进行诊治的结核性胸膜炎患者190例,根据随机信封抽签原则分为观察组与对照组各95例,两组都给予标准抗结核治疗方案,对照组在抗结核治疗的同时给予尿激酶治疗,观察组再给予地塞米松治疗,两组都治疗1个月。治疗后,比较两组的总有效率、不良反应的发生情况、胸腔积液完全引流时间、抽出胸腔积液总量、凝血酶原时间和凝血酶时间。结果:所有患者都注射耐受良好,未见严重并发症;观察组的总有效率(88.4%)明显高于对照组(72.6%);观察组胸腔积液完全引流时间和抽出胸腔积液总量分别为7.56±2.44d和2867.33±456.10 m L,对照组分别为9.44±2.89d和1989.92±444.20 m L,观察组胸腔积液完全引流时间明显短于对照组,且抽出胸腔积液总量显著高于对照组(P0.05)。治疗后,两组的凝血酶原时间和凝血酶时间都明显高于治疗前(P0.05),且观察组显著高于对照组(P0.05)。结论:地塞米松联合尿激酶治疗结核性胸膜炎能延长凝血酶时间和凝血酶原时间,缩短胸腔积液引流时间,增加抽出胸腔积液总量,安全性和临床疗效均较好。     

The validity of self-reported cancer diagnoses and factors associated with accurate reporting in a cohort of older Australian women

Epidemiological research often ascertains cancer history via self-reported questionnaires. We assessed the validity of self-reported cancer diagnoses in women born 1921-1926 recruited to the Australian Longitudinal Study in Women's Health (ALSWH) and determined the factors associated with false positive (FP) and false negative (FN) reporting. 4234 ALSWH cohort members were asked at baseline (1996) and in subsequent three-yearly surveys whether they had been diagnosed with specific cancers, including breast, cervical, lung and colorectal. We linked the cohort to the population-based New South Wales Central Cancer Registry (CCR) from 1972 to 2005 to identify registered invasive cancers. We calculated sensitivity, specificity and positive predictive value (PPV) of self-reported cancer diagnoses overall, at baseline (prevalent cancers) and follow-up (incident cancers) using the CCR diagnosis as the 'gold standard'. We used adjusted logistic regression to examine the determinants of FP and FN reports. Overall sensitivity was 89.2% (95% CI 86.0-91.7%) and exceeded 90% for breast, lung and colorectal cancer at baseline. Overall specificity was 96.9% (95% CI 96.3-97.5%), however, PPV was lower at 66.5% (95% CI 62.7-70.1%). FN reporting of any cancer at baseline was associated with being born overseas. Sensitivity and specificity of self-reported cancer diagnoses in this cohort of older women (aged 70-75 years at baseline) is high but PPV is comparatively lower. Hence, the use of linked data from population-based cancer registries is recommended for studies of cancer epidemiology. Particular attention must also be paid to country of birth in self-reported cancer data, as these findings suggest cancer will be under-reported by this group of women.     

A One Year Audit of Fine Needle Aspiration Cytology For the Pre-Operative Diagnosis of Breast Disease

In 1988, 985 patients presenting with breast disease, most with a palpable abnormality, were investigated by the triple approach (clinical examination, imaging and fine needle aspiration cytology [FNAC]). Using FNAC, 28% of patients were diagnosed as having carcinoma, 45% benign disease, 4% had suspicious cytology and 3% equivocal cytology. The remaining 20% had inadequate aspirates. Two false positive diagnoses of carcinoma were made (a false positive rate of 0.7%); one was a case of high grade non-Hodgkin's lymphoma and the other a papillary lesion with epithelial atypia. The false negative rate was 6.4%. Of these 49 patients, six had carcinoma-in-situ and 19 had low grade tumours. The absolute and complete sensitivities for the diagnosis of carcinoma in this series were 84.7% and 91.9% respectively and the absolute and complete specificities 99.7% and 98.3%, respectively. These figures compare favourably with those from other centres and confirm the efficacy of FNAC as part of the triple approach to the diagnosis of breast disease. The use of FNAC has resulted in a reduction in the number of Trucut and frozen section biopsies performed. Eighty three per cent of the patients with benign disease diagnosed by the triple approach have avoided excision biopsy, none of whom have subsequently been found to have carcinoma. Eighty patients with advanced breast carcinoma were spared operative intervention.     

A Systematic Review of Studies Comparing Diagnostic Clinical Prediction Rules with Clinical Judgment

Background

Diagnostic clinical prediction rules (CPRs) are developed to improve diagnosis or decrease diagnostic testing. Whether, and in what situations diagnostic CPRs improve upon clinical judgment is unclear.

Methods and Findings

We searched MEDLINE, Embase and CINAHL, with supplementary citation and reference checking for studies comparing CPRs and clinical judgment against a current objective reference standard. We report 1) the proportion of study participants classified as not having disease who hence may avoid further testing and or treatment and 2) the proportion, among those classified as not having disease, who do (missed diagnoses) by both approaches. 31 studies of 13 medical conditions were included, with 46 comparisons between CPRs and clinical judgment. In 2 comparisons (4%), CPRs reduced the proportion of missed diagnoses, but this was offset by classifying a larger proportion of study participants as having disease (more false positives). In 36 comparisons (78%) the proportion of diagnoses missed by CPRs and clinical judgment was similar, and in 9 of these, the CPRs classified a larger proportion of participants as not having disease (fewer false positives). In 8 comparisons (17%) the proportion of diagnoses missed by the CPRs was greater. This was offset by classifying a smaller proportion of participants as having the disease (fewer false positives) in 2 comparisons. There were no comparisons where the CPR missed a smaller proportion of diagnoses than clinical judgment and classified more participants as not having the disease. The design of the included studies allows evaluation of CPRs when their results are applied independently of clinical judgment. The performance of CPRs, when implemented by clinicians as a support to their judgment may be different.

Conclusions

In the limited studies to date, CPRs are rarely superior to clinical judgment and there is generally a trade-off between the proportion classified as not having disease and the proportion of missed diagnoses. Differences between the two methods of judgment are likely the result of different diagnostic thresholds for positivity. Which is the preferred judgment method for a particular clinical condition depends on the relative benefits and harms of true positive and false positive diagnoses.     

Scrub Typhus Meningitis in South India — A Retrospective Study

Background

Scrub typhus is prevalent in India although definite statistics are not available. There has been only one study on scrub typhus meningitis 20 years ago. Most reports of meningitis/meningoencephalitis in scrub typhus are case reports

Methods

A retrospective study done in Pondicherry to extract cases of scrub typhus admitted to hospital between February 2011 and January 2012. Diagnosis was by a combination of any one of the following in a patient with an acute febrile illness- a positive scrub IgM ELISA, Weil-Felix test, and an eschar. Lumbar puncture was performed in patients with headache, nuchal rigidity, altered sensorium or cranial nerve deficits.

Results

Sixty five cases of scrub typhus were found, and 17 (17/65) had meningitis. There were 33 males and 32 females. Thirteen had an eschar. Median cerebrospinal fluid (CSF) cell count, lymphocyte percentage, CSF protein, CSF glucose/blood glucose, CSF ADA were 54 cells/µL, 98%, 88 mg/dL, 0.622 and 3.5 U/mL respectively. Computed tomography was normal in patients with altered sensorium and cranial nerve deficits. Patients with meningitis had lesser respiratory symptoms and signs and higher urea levels. All patients had received doxycycline except one who additionally received chloramphenicol.

Conclusion

Meningitis in scrub typhus is mild with quick and complete recovery. Clinical features and CSF findings can mimic tuberculous meningitis, except for ADA levels. In the Indian context where both scrub typhus and tuberculosis are endemic, ADA and scrub IgM may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis.     

Comparison of loop-mediated isothermal amplification and real-time PCR for the diagnosis of tuberculous pleurisy

Aims: Tuberculous pleurisy is an important cause of pleural effusions in areas with a high incidence of tuberculosis. In this study, we developed an IS1081‐based LAMP for the detection of Mycobacterium tuberculosis complex and investigated its usefulness in the diagnosis of tuberculous pleurisy. Methods and Results: Investigation of pleural effusion samples from patients with tuberculous pleurisy, majority of them smear‐/culture‐negative, and control individuals with non‐TB diseases showed that the LAMP assay with incubation time of 60 min has much higher specificity and the LAMP assay with incubation time of 90 min has significantly higher sensitivity in the diagnosis of tuberculous pleurisy, as compared with fluorescent real‐time PCR. Conclusions: The MTBC–LAMP is a useful assay for the diagnosis of tuberculous pleurisy, especially in pleural effusion smear‐/culture‐negative patients. Significance and Impact of the Study: Tuberculous pleural effusion usually contains low number of mycobacteria, which leads to low diagnostic sensitivity of acid‐fast staining and mycobacterial culture methods. In this study, we developed a simple and sensitive LAMP assay for the diagnosis of tuberculous pleurisy. This assay should have broad application in resource‐limited settings.