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Influence of chest radiotherapy in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A Southwest Oncology Group Study.

The value of radiotherapy to the chest (RC) in disseminated small cell lung carcinoma (SCLC) has been questioned. Two protocols for disseminated SCLC from the Southwest Oncology Group (SWOG) have been compared. They were developed four years apart. The first one included radiotherapy (RT), 3000 rad in two weeks, to the primary tumor, mediastinum and supraclavicular areas, while the second one deleted any RC. Multidrug chemotherapy (CT) and brain RT were used in both protocols. Nonresponders to CT were removed from the study. Our main findings are as follows: (1) Initial chest relapses (patients with no initial extrathoracic relapse) have increased from 24-55% when RC is not given (P = 0.0001). Overall chest relapse (adding those patients that relapsed simultaneously in the chest plus other sites) in the second protocol was 73%. (2) Amount of response to CT does not influence the chances for relapse. Even complete responders to CT have a high chance for chest relapse. (3) Sites of relapse without RC are mainly in the primary tumor, ipsilateral hilus and mediastinum. (4) With RC, relapses shift to the chest periphery, mostly to the lung outside the radiotherapy field and to the pleura. (5) The two very different CT regimens have produced similar percentages and duration of response. (6) CT schema with periodic reinductions prolongs duration of response and survival over schema with continuous maintenance. Hence, interruption of CT to allow RC does not seem to adversely influence CT efficacy. From our results and the review of the literature we conclude that: (1) patients with disseminated SCLC that respond to CT should be given RC to decrease chest relapses. (2) A dose of 3000 rad in two weeks seems to be enough to produce a low percentage of chest relapse in disseminated SCLC, as survival of these patients is short and many will die prior to developing chest relapse. However, according to the literature, 4000-4800 rad is probably a more effective dose. (3) More studies and guidelines are needed to outline proper boundaries of radiotherapy fields, to decrease chances of peripheral chest relapses. (4) Median survival might not be a good parameter to evaluate the impact of RC in disseminated SCLC. The study of long-term survivors seems to be more important.

Carcinoma, Small Cell↗

The capacity of human malignant B-lymphocytes to disseminate in SCID mice is correlated with functional expression of the fibronectin receptor alpha 5 beta 1 (CD49e/CD29).

The alpha 5 beta 1 integrin (CD49e/CD29), a heterodimeric membrane protein, is the "classical" fibronectin receptor on many cell types. During B-cell ontogeny, expression of the alpha 5-subunit is developmentally regulated. The alpha 5 beta 1 is decisive for migration on fibronectin substrate and very likely cooperates with other adhesion molecules in transvascular trafficking. To test whether alpha 5 beta 1 influences local growth vs. disseminative spread of neoplastic B-cells in vivo, human B-cell lines mimicking different maturational stages were transferred s.c. into severe combined immunodeficiency (SCID) mice and examined for alpha 5 beta 1 expression and for adherence on fibronectin substrate in vitro and ex vivo. All cell lines were locally tumorigenic. Dissemination was observed in all animals carrying Nalm-6 tumors, in one animal with a BL 60 and in 2 mice carrying a Raji tumor. By contrast, Daudi, BJAB and U266 tumors did not disseminate. As evidenced by immunohistochemistry and flow cytometry, all lines and their tumors were to various extents beta 1-positive but showed considerable differences in alpha 5 expression. The functional surface expression of alpha 5 beta 1 correlated with fibronectin adherence of the lines. Daudi expressed alpha 5 beta 1 in a non-functional configuration which was rendered functional only upon applying high concentrations of Mg++ and Mn++. B-cell lines functionally expressing alpha 5 beta 1 at high or moderate levels disseminated in SCID mice while alpha 5-negative lines and Daudi did not. These results support the conclusion drawn from an earlier in situ analysis of human B-cell lymphomas/leukemias that the alpha 5 beta 1 integrin contributes to the disseminative phenotype of malignant B cells.

Animals↗

CNS disease following dissemination of SSPE measles virus from intraperitoneal inoculation of suckling hamsters.

Acute encephalitis was observed in suckling Golden Syrian hamsters following intraperitoneal (ip) inoculation of a hamster brain adapted strain of subacute sclerosing panencephalitis (SSPE) measles virus (HBS). Virus was isolated from the brains of all encephalitic animals by cocultivation of tissue with Vero cells. The histopathology of the encephalitis was characterized by perivascular mononuclear infiltrates, necrosis, eosinophilic inclusion bodies, and rare giant cells. Association of encephalitis with systemic viral infection was observed with virus present in lung and a kidney-spleen pool in addition to brain. Viral dissemination in asymptomatic animals was documented with virus being isolated from multiple non-neural tissues (spleen, lung, liver) of animals having no recoverable virus in their brains and no signs of encephalitis. Treatment of animals with cyclophosphamide prior to ip virus inoculation did not increase dissemination to brain. Absence of encephalitis in asymptomatic animals with proven viral dissemination to parenchymal organs indicates that neither viremia alone, nor viremia in conjunction with dissemination are sufficient conditions to establish central nervous system disease. The association of encephalitis with systemic viral infection and the dissemination to brain establish this model's potential value for the study of the pathogenesis of measles encephalitis.

Animals↗

Selective expansion of gammadelta T cells among liver-derived lymphocytes of AIDS patients with disseminated Mycobacterium avium complex infection.

The aim of this study was to investigate a potential expansion of gammadelta T cells in AIDS patients in response to disseminated infection with Mycobacterium avium complex. Liver-derived lymphocytes and peripheral blood lymphocytes were obtained from 5 AIDS patients with disseminated Mycobacterium avium complex infection and 10 HIV-infected patients without mycobacterial disease. Control patients included 14 HIV-negative patients without bacterial disease and 4 HIV-negative patients with disseminated Mycobacterium tuberculosis infection. The percentage of gammadelta T cells among CD3+ T lymphocytes was determined by flow cytometry. gammadelta T cells were markedly enhanced in liver biopsies but not among peripheral blood lymphocytes of AIDS patients with disseminated M. avium complex infection (median liver gammadelta/CD3: 26%) as compared to HIV-infected control patients without mycobacterial disease (median liver gammadelta/CD3: 2.3%; P < 0,005). Disseminated infection with M. tuberculosis in HIV-negative patients leads to a similar expansion of gammadelta T cells among liver-derived CD3+ lymphocytes (median gammadelta/CD3: 15.5%) as compared to control patients without mycobacterial disease (median gammadelta/CD3: 2.15%; P < 0,001).

AIDS-Related Opportunistic Infections↗

Are endometrial carcinoma cells disseminated at hysteroscopy functionally viable?

OBJECTIVE: The aim of this study was to evaluate the rate of transtubal dissemination of endometrial carcinoma cells by hysteroscopy and the functional viability of disseminated tumor cells by assessing cell adhesion in an in vitro model. METHODS: We studied 24 uteri obtained at TAH+BSO in patients with endometrial carcinoma. Further inclusion criteria were negative peritoneal cytology, no involvement of the uterine serosa or extrauterine disease, and endometrial surface involvement >1 cm in diameter. In vitro fluid hysteroscopy was performed with a 5-mm single-flow rigid hysteroscope. A maximum of 150 ml saline was infused at a maximum pressure of 100 mm Hg for a maximum of 3 min. Fluid running off through the tubes was collected. The cell suspension was enriched by a density gradient centrifugation. The isolated cells had a mean viability of 90% as judged by trypan blue exclusion. Viable cells (5 x 10(4) per 2-cm(2) polyvinyl chloride well plate) were cultured with equal parts of Dulbecco's modified Eagle's minimal essential medium and Ham's F-12 for 24 h. The endpoint of the analysis was the adherence of tumor cells to the polyvinyl chloride well plate, which was taken as a proxy for functional cell viability. Cytological evaluation was performed separately by two cytologists blinded to the source and date of the smears. RESULTS: Transtubal fluid dissemination was seen in 20 of 24 (83%) uteri. Tumor cells were found in 17 specimens (71%). In 10 (42%) specimens the disseminated tumor cells were functionally viable. CONCLUSIONS: Our model suggests that hysteroscopy can cause dissemination of malignant cells into the abdominal cavity from uteri containing endometrial carcinoma and that these cells can be functionally viable and adhere to a matrix.

Adenocarcinoma↗

Diagnosis of disseminated candidiasis in hospitalized patients using the Cand-Tec latex agglutination assay.

A total of 1,303 sera from 202 patients at risk for disseminated candidiasis were analyzed for the presence of Candida antigen using a commercially available latex agglutination test (Cand-Tec). Twenty-three patients had disseminated candidiasis documented by positive blood cultures, deep biopsy culture and histopathology or autopsy. Six patients had transient candidemia, 15 patients had candiduria, 62 patients were not colonized yet treated empirically with amphotericin B, and 46 patients were not colonized and not treated with amphotericin B. The sensitivity and specificity of the Candida antigen test for the diagnosis of disseminated candidiasis was 87% and 36% (threshold titer of greater than or equal to 1:2), 70% and 60% (greater than or equal to 1:4), and 30% and 85% (greater than or equal to 1:8), respectively. In contrast to previous studies we were unable to demonstrate a prognostic role for the Candida antigen test in patients with documented disseminated candidiasis. The lack of sensitivity and specificity of the Cand-Tec Candida antigen test precludes its use in the diagnosis of disseminated candidiasis.

Antigens, Fungal↗

[Value of radiotherapy in disseminated high-grade non-Hodgkin's lymphoma].

BACKGROUND: Radiotherapy is part of the treatment protocols in localized low-grade lymphomas as well as localized high-grade lymphomas adjunct to polychemotherapy. Integration of radiotherapy into the treatment of disseminated high-grade lymphomas is controversial. PATIENTS AND METHOD: The current literature and our own experience with radiotherapy as part of the treatment of disseminated high-grade lymphomas will be discussed. RESULTS: Retrospective analysis of large clinical trials suggest the value of radiotherapy in the treatment of disseminated high-grade lymphomas. Relapse occurs more frequently in non-irradiated regions than in fields of prior radiotherapy. Integration of radiotherapy into treatment protocols seems to be beneficial in patients with bulky disease. A dose/response relationship has been described. The few randomized trials, however, could not clearly demonstrate an advantage of radiotherapy adjuvant to chemotherapy in disseminated lymphomas. A possible advantage can be seen in patients who did not receive more than 4 cycles of polychemotherapy. CONCLUSION: Although the value of radiotherapy adjunct to polychemotherapy in disseminated high-grade lymphomas has not been proven in randomized studies retrospective analysis suggest an advantage. A large randomized study should clarify the role of radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Disseminated infection with Mycobacterium avium complex (MAC) in HIV infection].

EPIDEMIOLOGY: Disseminated MAC-infection is one of the most frequent opportunistic infections occurring in HIV-infected patients. Severely immunocompromised patients with CD4-counts < 50/microliter are at greatest risk for the disease. Survival of untreated infection is very poor (5 to 6 months). With therapy survival is prolonged by about 4 months. CLINICAL PRESENTATION AND DIAGNOSTIC PROCEDURES: The leading symptom of MAC-infection is fever eventually accompanied by weight lost, night sweats, enlarged lymph nodes, hepatosplenomegaly, abdominal pain and anemia. Blood cultures are very sensitive and the most appropriate examination. Other diagnostic procedures include bone marrow cultures, biopsies of the gastrointestinal tract, lymph nodes and the liver. Detection of MAC in sputum and stool samples only proves colonisation but not dissemination. However, colonisation of the gastrointestinal tract frequently precedes disseminated disease. THERAPY: Combination of clarithromycin, rifabutin and ethambutol has proven to be the most efficacious therapy and therefore has to be considered as standard therapy for disseminted MAC-infection. Problems most frequently encountered with this medication include uveitis (rifabutin) gastrointestinal disturbances (clarithromycin) and leucopenia (rifabutin) as well as drug interactions with protease-inhibitors (rifabutin). PROPHYLAXIS: Clarithromycin, rifabutin and azithromycin given as primary prophylaxis can diminish the risk of disseminated MAC-infection. Although a survival benefit has been seen with clarithromycin, primary prophylaxis of MAC-infection is not standard care in many centers. Reasons to withhold MAC-prophylaxis include lower incidence rates in some countries as well as possible side effects and drug interactions. CONCLUSION: Disseminated MAC-infection is a frequent opportunistic disease in HIV-infected persons who are severely immunocompromised. Antibiotic combination therapy with clarithromycin, rifabutin and ethambutol improves clinical symptoms and survival. Primary prophylaxis with different regimens is efficacious but the specific epidemiologic situation in each country has to be considered.

AIDS-Related Opportunistic Infections↗

[Detection of isolated disseminated tumor cells of colorectal carcinomas in lymph nodes].

The 5-year survival of patients with colorectal cancer UICC stage I and II ranges from 70% to 80%. Therefore, at least 20% to 30% of these patients develop recurrent disease, caused by hematogenic or lymphogenic tumor cell dissemination. Using immunohistochemical or molecular biological methods, disseminated tumor cells can be detected in lymph nodes in a high proportion of patients in UICC stage I or II. The detection of disseminated tumor cells could help to identify a subgroup of patients at risk for disease relapse who could benefit from adjuvant therapy. Lymphogenic tumor cell dissemination seems to be a very common event in early colorectal cancer, preceding hematogenic tumor cell dissemination. Although these observations appear to confirm the therapeutic importance of meticulous lymph node dissection, their prognostic relevance has yet to be determined in prospective studies.

Colorectal Neoplasms↗

Infectious and inflammatory dissemination are affected by ventilation strategy in rats with unilateral pneumonia.

OBJECTIVE: To evaluate the effect of V(T) reduction and alveolar recruitment on systemic and contralateral dissemination of bacteria and inflammation during right-side pneumonia. DESIGN: Interventional animal study. SETTING. University hospital research laboratory. SUBJECTS: A total of 54 male Wistar rats. INTERVENTIONS: One day after right lung instillation of 1.4x10(7) Pseudomonas aeruginosa, rats were left unventilated or ventilated for 2 h at low V(T) (6 ml/kg) with different strategies of alveolar recruitment: no PEEP, 8 cm H(2)O PEEP, 8 cm H(2)O PEEP in a left lateral position, 3 cm H(2)O PEEP with partial liquid ventilation, or high V(T) (set such as end-inspiratory pressure was 30 cm H(2)O) without PEEP (ZEEP). After ventilation the lungs, spleen and liver were cultivated for bacterial counts. Global bacterial dissemination was scored considering the percentage of positive spleen, liver and left lung cultures. TNF-alpha was assayed in plasma before and after mechanical ventilation. MEASUREMENTS AND RESULTS: All rats had right-side pneumonia with similar bacterial counts. All mechanical ventilation strategies, with the exception of low V(T)-PEEP 8, promoted contralateral lung dissemination. Overall bacterial dissemination was less in non-ventilated controls (22%) and low V(T)-PEEP 8 (22%) than in high V(T)-ZEEP (67%), low V(T)-PEEP 8 in left lateral position (59%) and low V(T)-ZEEP (56%) ( p<0.05). Partial liquid ventilation prevented systemic bacterial translocation, but at the expense of contralateral bacterial seeding. Plasma TNF-alpha concentration increased significantly after mechanical ventilation with no PEEP at both high and low V(T). CONCLUSIONS: Our results suggest that PEEP might reduce the risk of ventilation-induced bacterial and inflammatory mediator dissemination during pneumonia.

Animals↗

Inherited disorders of the IL-12-IFN-gamma axis in patients with disseminated BCG infection.

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN-gamma axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN-gamma circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN-gamma receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12Rbeta1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN-gamma circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN-gamma circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.

Adult↗

Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival.

PURPOSE: This prospective study evaluates the diagnostic potential of Cytokeratin 20 (CK 20) RT-PCR for the detection of disseminated tumor cells in bone marrow and blood of a large cohort of patients with ductal adenocarcinoma of the pancreas and the prognostic value on overall survival prediction. METHODS: Between 1994 and 2003, 172 patients (83 male, 89 female; 13-82 years) with pancreatic ductal adenocarcinoma underwent surgery. Bone marrow samples and venous blood were taken preoperatively and analyzed for disseminated tumor cells by nested CK 20 RT-PCR. RESULTS: Disseminated tumor cells were detected in 81 (47.1%) of the 172 patients in the bone marrow and/or the venous blood. Overall, in 45 of the 135 (33.3%) bone marrow samples and in 52 of the 154 (33.8%) blood samples, CK 20 positive cells were detected. Detection rates increased with the UICC-tumor stage. According to Kaplan-Meier, univariate survival analysis of all 172 patients (n = 78 R0-; n = 18 R1- and n = 5 R2-resected; n = 71 palliative surgery) showed a statistically significant relationship of overall survival to radicality of the operation (P < 0.0001), the UICC-stage of the tumors (P = 0.0011) and the detection of disseminated tumor cells in bone marrow and/or venous blood (P = 0.05). Patients with well- and moderately- differentiated tumors (G1 and G2) had a significantly longer survival (P = 0.045) than patients suffering from poorly differentiated tumors (G3). A positive CK 20 status in the bone marrow and/or blood within the group of patients with G1 and G2 tumors had a significantly negative prognostic impact on their survival (P = 0.046). CONCLUSIONS: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinoma by CK 20 RT-PCR. Detection rates are stage dependent, and survival analysis demonstrated statistically relevant data. From a clinical point of view, this finding is especially noteworthy for the group of well- and moderately-differentiated tumors.

Adenocarcinoma↗

Increased peritoneal dissemination after laparotomy versus pneumoperitoneum in a mouse cecal cancer model.

BACKGROUND: The effect of carbon dioxide (CO(2)) pneumoperitoneum on the liberation of cancer cells from the primary tumor is not clear. This study investigated the influence of laparotomy versus CO(2) pneumoperitoneum on the progression of colon cancer with serosal invasion in a mouse model. METHODS: Pieces of human colon adenocarcinoma (HT29) tumor were implanted in the cecal wall of 45 BALB/c nude mice. Each mouse underwent one of three procedures: laparotomy, CO(2) pneumoperitoneum, or anesthesia (control). Three weeks later, the size and weight of cecal tumors, the number of nodules, and the tumor volume score of peritoneal dissemination were examined. Another 45 mice were treated in the same way. The cecal tumor was resected on days 1, 3, or 5 after treatment. Total RNA was isolated from the resected tumors. The expression of E-cadherin and beta-1 integrin messenger RNA (mRNA) was examined by semiquantitative real-time reverse transcriptase-polymerase chain reaction assay. RESULTS: Significantly more nodules of peritoneal dissemination were found in the laparotomy group than in the control group (p < 0.05). The tumor volume score of peritoneal dissemination in the laparotomy group was significantly higher than in the other two groups (p < 0.05). The expression of E-cadherin mRNA at day 5 in the laparotomy group was significantly less than in the other two groups (p < 0.05). There were no differences in beta-1 integrin among three groups. CONCLUSIONS: Peritoneal dissemination was more extensive after laparotomy than after CO(2) pneumoperitoneum in a mouse model of cecal cancer with serosal invasion. Decreased expression of E-cadherin mRNA in tumors after laparotomy, but not after CO(2) pneumoperitoneum, may be associated with the increase in peritoneal dissemination.

Adenocarcinoma↗

Treatment of disseminated and progressive cavitary histoplasmosis with ketoconazole.

Ten patients with disseminated histoplasmosis and seven with progressive cavitary histoplasmosis were treated with ketoconazole, an imidazole derivative that is well absorbed orally and relatively nontoxic. Seven of seven noncompromised hosts with disseminated disease tolerated therapy well and achieved clinical and mycologic cures. Although well tolerated in all three compromised hosts with disseminated disease, none achieved clinical and bacteriologic cures. All patients with progressive cavitary disease tolerated therapy well and six of seven achieved clinical and radiographic cures. Therefore ketoconazole appears safe and effective in the treatment of disseminated or progressive cavitary histoplasmosis in the noncompromised host. In the compromised host with disseminated histoplasmosis, ketoconazole does not appear to be effective and more conventional therapy appears warranted.

Adult↗

Intracranial tumors with risk of dissemination in neuroaxis.

The experience of the Radiotherapy Service, Clínica Puerta de Hierro, Madrid (Spain), in the treatment of intracranial tumors with risk of neural axis dissemination is analyzed. In 15 years (1964-1979) 415 primary central nervous system tumors were studied and treated; 67 corresponded to tumors with risk of meningeal dissemination. Clinical dissemination in cerebrospinal fluid was proven in 14 patients. The actuarial survival of 10 years for patients with neural axis dissemination, without prophylactic treatment to the neuroaxis, is 14% with an average survival of 10.5 months. In approximately 20% of meduloblastomas, ependymal and pineal region tumors, meningeal metastases at some distance from the primary tumor can take place. Patients at risk wtih these types of neoplasia must be identified, and an adequate radical therapeutic focus devised, not only for the primary tumor, but also for the risk of dissemination.

Adolescent↗

Potential dissemination and persistence of Clostridium perfringens along the slaughtering process in French cattle, pig or poultry slaughterhouses.

Clostridium perfringens is a major foodborne pathogen associated with meat products, yet its dissemination routes and persistence within slaughterhouses remain poorly understood. In this study, whole-genome sequencing combined with multilocus sequence typing (MLST), core genome MLST (cgMLST), and core single nucleotide polymorphism (SNP) analysis was applied to 286 C. perfringens isolates collected from cattle, pig, and poultry slaughterhouses in France. MLST analysis revealed extensive genetic diversity, with most isolates assigned to novel allelic profiles rather than previously described sequence types. Phylogenetic analyses based on cgMLST and SNP data revealed frequent recovery of closely related isolates from feces, meat, surfaces, and air, highlighting widespread dissemination of strains within slaughterhouses during processing. Notably, close genetic related isolates recovered from air and other sample types are consistent with air-associated dissemination within slaughterhouse environments. In addition, the detection of closely related strains across different sampling campaigns suggests the potential persistence of C. perfringens within slaughterhouse environments over time. Most isolates were classified as toxinotype A (97.9%), with a few belonging to toxinotypes D (1.0%) and G (1.0%), and in silico analyses revealed a broad distribution of virulence-associated genes. Antimicrobial resistance genes (ARGs) were commonly detected, particularly those conferring resistance to tetracyclines, although isolates carrying multiple ARGs remained infrequent. Overall, this study provides new insights into the genomic diversity, dissemination pathways, and persistence of C. perfringens in multi-species slaughterhouses. These findings highlight the potential role of air-associated dissemination in contamination dynamics and underscore the importance of improved hygiene control strategies to mitigate food safety risks along the meat production chain.

Antimicrobial resistance gene (ARG)↗

Protecting patient privacy by quantifiable control of disclosures in disseminated databases.

One of the fundamental rights of patients is to have their privacy protected by health care organizations, so that information that can be used to identify a particular individual is not used to reveal sensitive patient data such as diagnoses, reasons for ordering tests, test results, etc. A common practice is to remove sensitive data from databases that are disseminated to the public, but this can make the disseminated database useless for important public health purposes. If the degree of anonymity of a disseminated data set could be measured, it would be possible to design algorithms that can assure that the desired level of confidentiality is achieved. Privacy protection in disseminated databases can be facilitated by the use of special ambiguation algorithms. Most of these algorithms are aimed at making one individual indistinguishable from one or more of his peers. However, even in databases considered "anonymous", it may still be possible to obtain sensitive information about some individuals or groups of individuals with the use of pattern recognition algorithms. In this article, we study the problem of determining the degree of ambiguation in disseminated databases and discuss its implications in the development and testing of "anonymization" algorithms.

Algorithms↗

Emergence of disseminated infections due to nontuberculous mycobacteria in non-HIV-infected patients, including immunocompetent and immunocompromised patients in a university hospital in Taiwan.

OBJECTIVES: Although disseminated nontuberculous mycobacteria (NTM) infection has been increasingly reported in patients with AIDS, this condition is still considered rare in non-HIV-infected patients. METHODS: We retrospectively reviewed the medical records of non-HIV-infected patients treated at National Taiwan University Hospital from January 1997 to December 2004 to search for epidemiological trends in disseminated NTM infection. Data analyzed included etiology, demographic characteristics, underlying disease, initial symptoms and signs, treatment, and outcomes. RESULTS: Disseminated NTM infections occurred in 15 non-HIV-infected patients during the study period. The mean age of these patients was 51 years (range 13-80). Among these patients, eight were males, and eight had various immunocompromised conditions. Fever was an initial presentation in 12 patients (80%). Diagnosis was made by positive blood (seven patients) or bone marrow culture (five patients) in the majority (73%) of patients. Infectious etiologies included Mycobacterium avium complex (MAC) in eight, rapidly growing mycobacteria (RGM) in four and Mycobacterium kansasii in three. The mean time from initial presentation to initiation of anti-NTM therapy was 130 days (ranged from 9 days to 17 months). Mortality was highest in patients with M. kansasii (100%), followed by RGM (25%) and MAC (12.5%). CONCLUSIONS: Although disseminated NTM infection is an emerging condition among patients without HIV infection, it is a condition which is associated with immune deficiency. A high level of clinical suspicion should be maintained for avoiding delayed diagnosis, especially in patients with underlying immunosuppression. Blood culture might play an important role in the early diagnosis of disseminated NTM disease. Early diagnosis can lead to appropriate diagnosis and reduce mortality.

Adolescent↗