Evaluation of medical decision support systems (DDX generators) using real medical cases of varying complexity and origin.

BACKGROUND: Medical decision support systems (CDSSs) are increasingly used in medicine, but their utility in daily medical practice is difficult to evaluate. One variant of CDSS is a generator of differential diagnoses (DDx generator). We performed a feasibility study on three different, publicly available data sets of medical cases in order to identify the frequency in which two different DDx generators provide helpful information (either by providing a list of differential diagnosis or recognizing the expert diagnosis if available) for a given case report. METHODS: Used data sets were n = 105 cases from a web-based forum of telemedicine with real life cases from Afghanistan (Afghan data set; AD), n = 124 cases discussed in a web-based medical forum (Coliquio data set; CD). Both websites are restricted for medical professionals only. The third data set consisted 50 special case reports published in the New England Journal of Medicine (NEJM). After keyword extraction, data were entered into two different DDx generators (IsabelHealth (IH), Memem7 (M7)) to examine differences in target diagnosis recognition and physician-rated usefulness between DDx generators. RESULTS: Both DDx generators detected the target diagnosis equally successfully (all cases: M7, 83/170 (49%); IH 90/170 (53%), NEJM: M7, 28/50 (56%); IH, 34/50 (68%); differences n.s.). Differences occurred in AD, where detection of an expert diagnosis was less successful with IH than with M7 (29.7% vs. 54.1%, p = 0.003). In contrast, in CD IH performed significantly better than M7 (73.9% vs. 32.6%, p = 0.021). Congruent identification of target diagnosis occurred in only 46/170 (27.1%) of cases. However, a qualitative analysis of the DDx results revealed useful complements from using the two systems in parallel. CONCLUSION: Both DDx systems IsabelHealth and Memem7 provided substantial help in finding a helpful list of differential diagnoses or identifying the target diagnosis either in standard cases or complicated and rare cases. Our pilot study highlights the need for different levels of complexity and types of real-world medical test cases, as there are significant differences between DDx generators away from traditional case reports. Combining different results from DDx generators seems to be a possible approach for future review and use of the systems.

[Fine-needle aspiration (FNA) of the thyroid gland : Analysis of discrepancies between cytological and histological diagnoses]. / Feinnadelaspiration (FNA) der Schilddrüse : Analyse diskrepanter zytologischer und histologischer Diagnosen.

BACKGROUND: Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail. OBJECTIVES: Investigation of causes and relevance of discrepant diagnoses. MATERIALS AND METHOD: The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined. RESULTS: Malignant tumors were found in 45 patients (15.1 %). In 5 patients the cytological diagnosis was "false negative". Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis "suspicious of malignancy" or "malignant," 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity. CONCLUSIONS: Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.

[A plea for cytopathology]. / Ein Plädoyer für die Zytopathologie.

Compared to other European and non-European countries the benefits of cytopathology for the diagnosis of many tumors is still underestimated in Germany for traditional reasons. Cytological methods provide excellent material from many organs for morphological, immunochemical and molecular examinations so that a definitive diagnosis is cytologically possible in many cases and the number of exploratory surgical operations could therefore be reduced. Improvements in this deplorable situation will only be possible if a standardized training period in cytology is consistently included in the training of general pathologists. This requires organizational and infrastructural changes within the institutes of pathology. In this respect, the university institutes as important training institutions should lead the way.

[Cytology of the urinary tract: Between uncertainty and clarity]. / Zytologie der ableitenden Harnwege: Zwischen Zweifel und Gewissheit.

Reliable detection of poorly differentiated urothelial carcinoma and the detection of carcinoma in situ, which is often invisible by cystoscopy, are the undisputed strength of urinary cytology. In contrast, well-differentiated urothelial tumors are often missed by cytology. We suggest the following classification: negative, questionable, suspicious, and positive. Due to the complex clinico-pathological associations, the classification should always be accompanied by an appropriate commentary. The WHO 2004 classification separates the clinically less important low-grade tumors from the clinically relevant high-grade tumors, usually classified as "positive" by cytology. A cytological diagnosis of low-grade tumors by cytology is of minor clinical importance. Most urothelial neoplasias are characterized by chromosomal aberrations. This makes multi-target fluorescence in situ hybridization (FISH) assay suitable for the clarification of non-definitive cytology. In contrast, positive cytology does not need further confirmation by FISH analysis. Standardized diagnosis and the possibility for supplementary analyses increase the diagnostic value of urinary cytology.

Peritoneal mesothelioma after environmental asbestos exposure.

Mesothelioma are primary malignant neoplasms of the serous membranes. They usually involve the pleura and rarely the pericardium, the peritoneum and the tunica vaginalis testis. About 90% are associated with exposure to asbestos. The exposure is generally occupational, an environmental inhalation of asbestos and asbestiform fibers in areas in Turkey has been observed and presents a major health problem. This report of a patient from Anatolia with peritoneal mesothelioma after environmental exposure outlines the importance of considering this pathology in the differential diagnosis of a Turkish patient presenting with ascites.

Invasive pulmonary aspergillosis: effects of early resection in a neutropenic rat model.

OBJECTIVE: Invasive pulmonary aspergillosis is frequent in neutropenic patients. Usually localized in the beginning, the disease spreads and mortality is high despite antifungal treatment. The role of early adjuvant surgery is not clear. Surgery may help to confirm fungal disease, may control fungal disease locally and may prevent systemic spreading. This study examines effects of early resection on survival and dissemination in a rat model of localized invasive pulmonary aspergillosis. METHODS: Forty persistently neutropenic male albino rats were challenged with standardized conidial aspergillus inoculum injected into peripheral lung tissue of the right upper lobe under direct vision. Animals were divided into four groups. Twenty animals were treated with amphotericin B at 1 mg/kg per day beginning 48 h after inoculation, 20 animals were left untreated. In each group half the animals underwent early resection of localized invasive aspergillosis by lobectomy. Animals were checked daily and mortality was recorded up to 28 days after which surviving animals were sacrificed. RESULTS: Significantly higher survival was observed in resected animals in the non-Am B groups (survival: 10 +/- 19% without early resection and 50 +/- 32% with early resection; P = 0.044). However, early resection did not lead to improved survival in animals treated with amphotericin B (survival 70 +/- 29% without early resection and 50 +/- 32% with early resection; P = 0.316). CONCLUSIONS: In this rat model of localized invasive pulmonary aspergillosis effects of early resection on survival could be demonstrated only in animals not receiving amphotericin B treatment.

Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?

Even though complete resection is regarded as the only curative treatment for nonsmall cell lung cancer (NSCLC), >50% of resected patients die from a recurrence or a second primary tumour of the lung within 5 yrs. It remains unclear, whether follow-up in these patients is cost-effective and whether it can improve the outcome due to early detection of recurrent tumour. The benefit of regular follow-up in a consecutive series of 563 patients, who had undergone potentially curative resection for NSCLC at the University Hospital, was analysed. The follow-up consisted of clinical visits and chest radiography according to a standard protocol for up to 10 yrs. Survival rates were estimated using the Kaplan-Meier analysis method and the cost-effectiveness of the follow-up programme was assessed. A total of 23 patients (6.4% of the group with lobectomy) underwent further operation with curative intent for a second pulmonary malignancy. The regular follow-up over a 10-yr period provided the chance for a second curative treatment to 3.8% of all patients. The calculated costs per life-yr gained were 90,000 Swiss Francs. The cost-effectiveness of the follow-up protocol was far above those of comparable large-scale surveillance programmes. Based on these data, the intensity and duration of the follow-up was reduced.

Simultaneous occurrence of 2 HIV-related immunereconstitution diseases after initiation of highly active antiretroviral therapy.

The case of a 44-y-old woman with HIV infection and cytomegalovirus retinitis in whom antiretroviral therapy (HAART) revealed pulmonary cryptococcosis is presented. Pulmonary cryptococcosis occurred simultaneously with immune recovery uveitis after starting HAART, showing that complex clinical pictures may arise from immunreconstitution diseases.

Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings.

The aim of this study was to evaluate the UroVysion (Vysis, Downers Grove, IL) fluorescence in situ hybridization (FISH) test for improved detection of bladder cancer in urinary specimens. Three groups of specimens were examined, including voided urine specimens (1) collected before resection of bladder cancer, (2) from cystoscopically negative bladders of patients with previous bladder cancer, and (3) from patients with benign prostatic hyperplasia (controls). FISH positivity was defined as more than 2 urothelial cells with an abnormal signal copy number of at least 1 of the 4 probes. FISH was positive in 1 of 27 control specimens and in 33 (73%) of 45 pTa, 12 (100%) of 12 pT1, and 13 (100%) of 13 pT2-4 tumors. The results were similar in a series of 68 bladder washings. In addition, FISH of voided urine specimens was positive in 5 of 10 patients with negative follow-up cystoscopy results. Subsequent recurrence was found in 4 of these patients but in none of 5 patients with FISH-negative results. Multiprobe FISH markedly improves the sensitivity and specificity of cytology for the detection of bladder cancer in urine specimens.

Pulmonary cytomegalovirus infection in immunocompromised patients.

BACKGROUND: Cytomegalovirus (CMV) infection and CMV disease are frequent complications in immunocompromised patients. In this study, the incidence of pulmonary CMV infection was analyzed in different groups of immunocompromised patients and the diagnostic value of immunostaining with anti-CMV antibodies in BAL cells was evaluated in regard to the diagnosis of CMV pneumonitis. METHODS: Five hundred eighty consecutive BAL procedures were analyzed prospectively in 442 immunocompromised and 126 nonimmunocompromised control subjects. CMV culture in BAL fluid was performed by shell vial assay and immunostaining using three monoclonal anti-CMV antibodies. RESULTS: The incidence of culture results positive for CMV in the BAL fluid varied from 20 to 30% in HIV-positive patients, in patients following stem cell or renal transplantation, and in patients with autoimmune disease or lung fibrosis treated with immunosuppressive agents. CMV was cultured from 4.4% of BALs in patients treated with high-dose chemotherapy and from 2.4% of control subjects. CMV disease developed in 37 patients; in 18 of these patients, CMV pneumonitis was present. The results of CMV immunostaining were positive in a total of 22 BALs, all in patients with CMV disease. The sensitivity, specificity, and positive and negative predictive values of positive CMV immunostaining results for the diagnosis of CMV pneumonitis were 88.9%, 98.6%, 72.7%, and 99.5%, respectively. CONCLUSION: The incidence of pulmonary CMV infection is similar in different groups of immunocompromised patients except for patients following high-dose chemotherapy. CMV immunostaining in the BAL fluid is a very helpful method to diagnose CMV pneumonitis in these patients.

Severe bronchiolitis in acute Mycoplasma pneumoniae infection.

We report on a 17-year-old patient with severe bronchiolitis due to Mycoplasma pneumoniae infection. Despite an early 10-day course of clarithromycin, she developed progressive dyspnea, cough, fever, and severe obstructive ventilatory impairment. Sixteen days after onset of the disease a severe hemolytic anemia developed with only cold agglutinins positive at serologic screening. Thoracoscopic lung biopsy revealed diffuse bronchiolitis with suppurative intrabronchiolar inflammation, lymphohistiocytic "cuffing" of the bronchioli, and foam cell aggregates within neighboring alveoli. The infiltrate consisted mainly of CD3+, CD8+ lymphocytes and CD68+ macrophages. The diagnosis of Mycoplasma pneumoniae bronchiolitis was based on repeated complement fixation tests, which turned strongly positive only at day 74 after onset of the disease. Pulmonary function improved slowly under long-term prednisone treatment.

Urinary level of nuclear matrix protein 22 in the diagnosis of bladder cancer: experience with 130 patients with biopsy confirmed tumor.

PURPOSE: We prospectively evaluated the value of nuclear matrix protein 22 (NMP22dagger) and cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: We analyzed NMP22 in voided urine from 235 patients before cystoscopy. Of the patients 130 had transitional cell carcinoma of the bladder and subsequently underwent surgery. In a subset of 200 patients bladder washout samples for cytology were collected during cystoscopy. The cutoff for NMP22 was 10.0 units per ml. For cytology only high grade atypia was considered positive. RESULTS: Histology showed 77 superficial (pTa, pTis) and 53 invasive (pT1 or greater) tumors. Sensitivity of NMP22 was 51% and specificity was 83%. NMP22 sensitivity was 36% for superficial tumors and 73% for invasive transitional cell carcinoma. Overall sensitivity of cytology was 52% and specificity was 89%. Cytology sensitivity was 38% for superficial tumors and 83% for invasive transitional cell carcinoma. NMP22 sensitivity for grades 1, 2 and 3 tumors was 30%, 56% and 68%, respectively. Cytology sensitivity for grades 1, 2 and 3 tumors was 30%, 50% and 91%, respectively. Combined NMP22 and cytology had a sensitivity of 70%. CONCLUSIONS: NMP22 has sensitivity and specificity similar to those of cytology from bladder washout samples. Particularly in low stage and low grade tumors both tests show the same disappointing sensitivity. Because of a false-negative rate of 49%, NMP22 cannot replace cystoscopy in clinical practice, as the danger of missing NMP22 negative tumors is too high to rely on its results in an individual patient.

Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy.

BACKGROUND: Reactivation of polyomavirus type BK (BK virus) is increasingly recognized as a cause of severe renal-allograft dysfunction. Currently, patients at risk for nephropathy due to infection with the BK virus are identified by the presence of cells containing viral inclusion bodies ("decoy cells") in the urine or by biopsy of allograft tissue. METHODS: In a retrospective analysis, we performed polymerase-chain-reaction assays for BK virus DNA in plasma samples from 9 renal-allograft recipients with BK virus nephropathy; 41 renal-allograft recipients who did not have signs of nephropathy, 16 of whom had decoy cells in the urine; and as immunocompromised controls, 17 patients who had human immunodeficiency virus type 1 (HIV-1) infection (stage C3 according to the classification of the Centers for Disease Control and Prevention) and who had not undergone transplantation. RESULTS: In all nine patients with BK virus nephropathy, BK virus DNA was detected in the plasma at the time of the initial histologic diagnosis (a mean [+/-SD] of 46+/-28 weeks after transplantation) and during the course of histologically diagnosed, persistent BK virus disease. In three of the six patients with nephropathy who were studied serially after transplantation, BK virus DNA was initially undetectable but was detected 16 to 33 weeks before nephropathy became clinically evident and was confirmed by biopsy. Tests for BK virus DNA in plasma became negative and the nephropathy resolved after the doses of immunosuppressive drugs were decreased in two patients and after removal of the renal allograft in three patients. BK virus DNA was found in the plasma of only 2 of the 41 renal-allograft recipients who had no signs of nephropathy and in none of the patients with HIV-1 infection. CONCLUSIONS: Testing for BK virus DNA in plasma from renal-allograft recipients with use of the polymerase chain reaction is a sensitive and specific method for identifying viral nephropathy.

Granulomatous Pneumocystis carinii pneumonia in Wegener's granulomatosis.

This study reports on a first case of granulomatous Pneumocystis carinii pneumonia (PCP) in a human immunodeficiency virus-negative patient with antineutrophil cytoplasmic antibody-positive Wegener's granulomatosis whilst receiving immunosuppressive treatment. The patient presented with diffuse alveolar haemorrhage, pauci-immune rapid progressive glomerulonephritis and leukocytoclastic vasculitis of the skin. Granulomatous Pneumocystis carinii pneumonia developed under immunosuppressive treatment with cyclophosphamide and prednisone. At the time Pneumocystis carinii pneumonia developed, there was a marked lymphopenia with a very low CD8+ cell count in the blood. Grocott staining in bronchoalveolar lavage fluid revealed no Pneumocystis carinii. The diagnosis was made via a video-assisted thoracoscopic lung biopsy which showed granulomas containing high numbers of Pneumocystis carinii cysts.

[Rapidly progressing respiratory insufficiency of uncertain etiology]. / Rasch progrediente respiratorische Insuffizienz unklarer Atiologie.

In a 59-year-old male patient, chronic dry cough and dyspnoea on exertion preexisting for several years became rapidly progressive within a few weeks prior to hospitalisation. He died one month after admission from respiratory failure. Three months before admission, history, pulmonary function tests, and computed tomography (CT) of the chest revealed no evidence of asthma, COPD, or any other lung disease. Clinical examination showed no clubbing, but end-inspiratory velcro-rales were audible over both lungs. Inhaled steroids and diuretics did not bring clinical amelioration. On admission there were basal consolidations, bronchiectases, and predominant fibrotic changes with honeycombing and subpleural thickening over both lungs, in the absence of any ground-glass pattern in the CT. At the same time lymphocytosis predominated in bronchoalveolar lavage (BAL). The search for pneumonia, viral infection, tumour, vasculitis, or a drug-related disorder remained negative. Pathological examination at autopsy showed nonuniform fibrosing alveolitis.

[A "typical" case of pulmonary embolism]. / Ein "typischer" Fall von Lungenembolien.

A 85-year-old woman was admitted to our hospital because of a presumtive diagnosis of pulmonary thromboembolism. The patient presented with a history of progressive dyspnoea and retrosternal pain. 3-4 weeks ago she had noticed a swollen left leg. On examination a 4/6-pansystolic murmur was found. An arterial blood gas analysis showed a reduced oxygen saturation. An electrocardiogram revealed deep S-waves in lead I and pathological Q-waves in lead III. The chest X-ray showed cardiomegaly, a pulmonary nodule and an ill-defined opacity inferioposteriorly. Ventilation-perfusion mismatch was demonstrated by lung ventilation-perfusion scanning. Transthoracic echocardiography showed pulmonary hypertension and tricuspid regurgitation. On the 20th hospital day the patient died from multi organ failure. Pulmonary thromboembolism secondary to deep venous thrombosis of the lower extremities was the most likely diagnosis. In view of the patients' history of night sweat, loss of appetite and weight loss a malignant process had to be taken into consideration. A tumor originating from the right ventricle, the right ventricular outflow tract or the pulmonary artery was compatible with the clinical picture of multiple pulmonary emboli. On autopsy a polymorph cellular sarcoma measuring 6 x 3 x 3 cm was found in the right ventricular outflow tract. Section of the lung revealed a single pulmonary metastasis and multiple thromboemboli of various age. Pulmonary artery sarcomas, as described in our case, are extremely rare. The prognosis is poor and often the diagnosis is only made on autopsy.

The value of transbronchial needle aspiration in the diagnosis of peripheral pulmonary lesions.

BACKGROUND: Transbronchial needle aspiration (TBNA) is a bronchoscopic sampling technique used for the diagnostic workup of mediastinal lymph nodes, but the value of its routine use in evaluating peripheral pulmonary lesions is not yet firmly established. DESIGN: Retrospective analysis of routine diagnostic bronchoscopies. SETTING: University teaching hospital. PATIENTS AND METHODS: One hundred seventy-two consecutive patients (126 with malignant and 46 with nonmalignant disease) who underwent bronchoscopy for a peripheral pulmonary lesion. RESULTS: In 87 patients (51%), a final diagnosis was established by bronchoscopy; diagnoses included 81 malignant lesions (69 lung cancer and 12 pulmonary metastases) and 6 benign lesions (all tuberculosis). TBNA was used in 152 of the 172 patients (89%). Other endoscopic techniques included bronchial washing (100%), bronchial brushing (45%), and transbronchial biopsy (TBB) (27%). Concerning the different bronchoscopic sampling techniques, TBNA showed a positive result in 35% of cases, in comparison to 17% for TBB, 22% for bronchial washing, and 30% for bronchial brushing. While TBNA was diagnostic in 27.5% of the malignant lesions < 3 cm in diameter, the success rate in lesions > 3 cm was 65.5% (p = 0.03). Endoscopy-related complications included pneumothorax (n = 1), self-limiting bleeding (n = 12), prolonged coughing (n = 2), and vasovagal reactions (n = 2). None of these complications required further treatment. CONCLUSION: TBNA is an effective bronchoscopic sampling technique in the diagnosis of peripheral pulmonary lesions. In our study, the use of TBNA increased the diagnostic yield of bronchoscopy from 35 to 51% without additional risk. The use of TBNA in the clinical routine should be encouraged.