Evolution of Clinical Characteristics and Outcomes of Critically Ill Patients 90 Years Old or Older Over a 12-Year Period: A Retrospective Cohort Study.

OBJECTIVES: The global population is aging, and the proportion of very elderly patients 90 years old or older in the ICU is expected to increase. The changes in the comorbidities and outcomes of very elderly patients hospitalized in the ICU that have occurred over time are unknown. DESIGN: Retrospective observational cohort study. SETTING: ICUs at a single academic hospital in Germany. PATIENTS: Ninety years old or older and admitted to the ICU between January 1, 2008, and April 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 92,958 critically ill patients, 1,108 were 90 years old or older. The study period was divided into two halves: January 1, 2008-August 30, 2013, and September 1, 2013-April 30, 2019. The number of patients 90 years old or older increased from the first period ( n = 391; 0.90% of total admissions) to the second period ( n = 717; 1.44%). The patients' demographic characteristics were similar between the both time periods. The median Charlson Comorbidity Index was higher during the first period (1 [interquartile range, 1-3]) than compared with the second time period (1 [0-2]; p = 0.052). The Simplified Acute Physiology Score (SAPS) II was higher during the first time period (38 [29-49]) than during the second period (35 [27-45]; p = 0.005). Vasopressor therapy was necessary in 40% ( n = 158) and 43% ( n = 310) of patients in each time period, respectively ( p = 0.363). Invasive mechanical ventilation was administered in 37% ( n = 146) and 34% ( n = 243) of patients in each time period, respectively ( p = 0.250). The median length of the ICU stay was significantly lower in the first time period than in the second time period (1.4 vs. 1.7 d; p = 0.002). The ICU (18% vs. 18%; p = 0.861) and hospital (31% vs. 29%; p = 0.395) mortality rates were comparable between the two groups. The 1-year mortality was significantly lower during the second time period than during the first time period (61% vs. 56%; p = 0.029). Cox regression analysis revealed that the SAPS II, medical cause of admission, mechanical ventilation requirement, and vasopressor use were associated with 1-year mortality. CONCLUSIONS: The number of patients 90 years old or older who were treated in the ICU has increased in recent years. While the patients' clinical characteristics and short-term outcomes have not changed significantly, the long-term mortality of these patients has improved in recent years.

Rapid Diagnosis of Recurrent Paucibacillary Tuberculosis.

Introduction: The rapid diagnosis of tuberculosis recurrence can be challenging due to persistently positive detection of Mycobacterium tuberculosis-specific DNA from sputum and bronchopulmonary samples in the absence of active disease. Methods: We compared the diagnostic accuracy of the detection of M. tuberculosis-specific DNA by either Xpert (January 2010-June 2018) or Xpert Ultra (July 2018-June 2020) and M. tuberculosis-specific ELISPOT in bronchoalveolar lavage (BAL) samples with M. tuberculosis culture results from sputum or bronchopulmonary samples in patients with suspected recurrence of pulmonary tuberculosis. Results: Among 44 individuals with previous tuberculosis and a presumptive diagnosis of recurrent pulmonary tuberculosis, 4/44 (9.1%) were diagnosed with recurrent tuberculosis by culture. DNA of M. tuberculosis was detected by Xpert in BAL fluid in 1/4 (25%) individuals with recurrent tuberculosis and in 2/40 (5%) cases with past tuberculosis without recurrence, while BAL-ELISPOT with a cut-off of >4,000 early secretory antigenic target-6-specific or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 million BAL-lymphocytes was positive in 4/4 (100%) individuals with recurrent tuberculosis and in 2/40 (5%) cases of past tuberculosis without recurrence. Conclusion: M. tuberculosis-specific BAL-ELISPOT is more accurate than BAL-Xpert for the diagnosis of paucibacillary tuberculosis recurrence.

Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological methods.

Diagnosing pulmonary tuberculosis (TB) may be delayed until culture results become available.We ascertained the accuracy of a stepwise diagnostic algorithm for the rapid diagnosis of pulmonary TB by GeneXpert from sputum and/or bronchoalveolar lavage (BAL) followed by a Mycobacterium tuberculosis-specific BAL ELISPOT assay in patients with a suspected diagnosis of pulmonary TB at a clinical referral centre in Germany.Among 166 patients with a presumptive diagnosis of pulmonary TB, 81 cases were confirmed by M. tuberculosis culture from sputum and/or BAL. In 66 out of 81 (81.5%) cases, patients initially had M. tuberculosis detected by GeneXpert from sputum; in addition, six out of 81 (7.4%) cases were diagnosed by GeneXpert on BAL fluid (together 72 out of 81 (88.9%) patients). Out of the remaining nine patients with negative GeneXpert results from sputum and BAL, BAL ELISPOT identified eight patients with culture-confirmed TB correctly (median time to culture positivity 26 days). At a cut-off of >4000 early secretory antigenic target-6- or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 000 0000 lymphocytes, the specificity of the BAL ELISPOT for active TB was 97%.In low TB incidence countries, nearly all patients with active pulmonary TB can be identified within the first few days of clinical presentation using a stepwise strategy with GeneXpert and BAL ELISPOT.

Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study.

RATIONALE: The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears. OBJECTIVES: Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay. METHODS: Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB. CONCLUSIONS: Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.

Antimycobacterial immune responses in patients with pulmonary sarcoidosis.

INTRODUCTION: Sarcoidosis is a multisystem granulomatous disease of unknown origin. Pathogenetic involvement of Mycobacterium tuberculosis has frequently been discussed in the aetiology of sarcoidosis; however, studies still remain contradictory. OBJECTIVE: We addressed the question of mycobacterial involvement in the pathogenesis of sarcoidosis by analysing cellular immune responses to mycobacterial antigens. METHODS: We examined the interferon (IFN)-gamma production by enzyme-linked immunospot in response to purified protein derivate (PPD) mycobacterial-specific antigen early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10 by peripheral blood mononuclear cells (PBMCs) and bronchoalveolar-lavage mononuclear cells (BALMCs) of patients with pulmonary sarcoidosis, smear-negative tuberculosis and controls. RESULTS: Release of IFN-gamma in response to ex vivo contact with PPD, ESAT-6 or CFP-10 by BALMC and PBMC were comparable among patients with sarcoidosis and controls (PBMC P = 0.2326; BALMC P = 0.1767) and were less frequently observed in both groups compared to patients with tuberculosis (BALMC P < 0.05; PBMC P < 0.0001). Within PBMC, the immunophenotype of sarcoidosis patients differed from that of patients with tuberculosis, as well as from that of controls, while within BALMC it resembled that of patients with tuberculosis. CONCLUSION: In contrast to patients with tuberculosis, the frequency of mycobacteria-specific local and systemic immune responses is not elevated in patients with sarcoidosis when compared to controls. The immunophenotype represents the local resemblance of the granulomatous reaction underlying tuberculosis and sarcoidosis while showing systemical difference. These observations do not support a role of an infection with M. tuberculosis in the pathogenesis of sarcoidosis.

Subglottic MALT lymphoma of the larynx--more attention to the glottis.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx is a rare but well-documented entity which may arise from chronic inflammatory process. Supraglottic left regions are predominant due to unknown reason. CASE REPORT: We present the case of a 62-year-old man with a dry cough, stridor and developing exertional dyspnea. This subglottic almost circumferential MALT lymphoma showed a temporary distinct disappearance after cortisone administration during the diagnostic process. Bronchoscopy confirmed the diagnosis of a primary MALT lymphoma of the larynx. The patient received chemotherapy according to CHOP scheme plus rituximab. A reliable post-treatment care period of 15 months showed no sign of recurrence. CONCLUSION: MALT lymphoma of the larynx are believed to arise from preexisting or acquired lymphoid tissue of the upper airway. Acquired lymphoid tissue is documented in the supraglottic region and may be associated with a chronic inflammatory process. However, in subglottic cases it is unclear whether the chronic inflammation arises from a local or systemic process.

Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot.

RATIONALE: In a large proportion of patients with active pulmonary tuberculosis (pTB), acid-fast bacilli smear results for sputum and bronchial secretions are negative. Detectable growth of Mycobacterium tuberculosis (MTB) in cultures takes several weeks and MTB-specific DNA amplification results on sputum and bronchial secretions are variable in these patients. OBJECTIVE: We investigated whether a rapid diagnosis of pTB can be established by enumeration of MTB-specific mononuclear cells from bronchoalveolar lavage (BAL) fluid in routine clinical practice. METHODS: Patients presenting to a tertiary hospital with medical histories and pulmonary infiltrates compatible with tuberculosis, and negative acid-fast bacilli smear results (three) from sputum, were prospectively enrolled in this study. An MTB-specific enzyme-linked immunospot assay (ELISPOT [T-SPOT.TB; Oxford Immunotec, Abingdon, UK]) with early antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides was performed on peripheral blood mononuclear cells (PBMCs) and mononuclear cells from the BAL fluid (BALMCs). MEASUREMENTS AND MAIN RESULTS: Of 37 patients, 12 were found to have smear-negative pTB and 25 were found to have an alternative diagnosis. Patients with tuberculosis had a median number of 17 ESAT-6-specific cells and 24.5 CFP-10-specific cells per 200,000 PBMCs and 37.5 ESAT-6-specific cells and 49.5 CFP-10-specific cells per 200,000 cells in the BAL fluid. Control patients had a median of 1 ESAT-6-specific cell and 1 CFP-10-specific cell per 200,000 PBMCs and no ESAT-6- and CFP-10-specific cells per 200,000 cells in the BAL fluid (p < 0.0001). All patients with TB but none of the control subjects had more than 5 spot-forming cells per 200,000 BALMCs with either peptide in the BAL fluid ELISPOT. CONCLUSION: Smear-negative pulmonary tuberculosis can be diagnosed rapidly by identification of MTB-specific cells in the BAL fluid.

Enhanced expression of selenocysteine lyase in acute glomerulonephritis and its regulation by AP-1.

Acute glomerulonephritis can lead to chronic glomerulonephritis or resolve without permanent damage to the kidneys. Differential gene expression was studied in a model of acute and chronic glomerulonephritis to identify factors influencing the course of glomerulonephritis towards healing or chronification. One of the differentially expressed genes was identified as SCL, encoding selenocysteine lyase. Its expression was higher in acute glomerulonephritis and lower in chronic glomerulonephritis. The transcriptional regulation of SCL was studied in vitro in rat mesangial cells (MC). SCL RNA expression increased eight-fold compared to the baseline after stimulation with interleukin-1beta (IL-1beta) for three hours. Luciferase expression and gel shift experiments revealed an enhancer element between bp -152 and -298 of the SCL 5'-regulatory region, with protein binding to an AP-1 binding site that may be involved in the regulation of SCL-RNA in vivo in an endogenous feedback mechanism to the inflammatory reaction in acute glomerulonephritis, leading to resolution of this disease.