[Arthritis and pulmonary cavities]. / Arthritiden und Lungenkavernen.

This case report describes the very rare simultaneous occurrence of rheumatoid arthritis and granulomatosis with polyangiitis with the only organ manifestation of life-threatening bilateral pulmonary cavities. Due to the acuteness of the vasculitis, treatment was primarily with cyclophosphamide infusions and high-dose glucocorticoids, and in the further course with high-dose methotrexate. Routine thoracic imaging also seems to be useful when conventional basic rheumatologic treatment is newly initiated, as treatment-decisive changes are seen with a relevant frequency. The occurrence of both autoimmune diseases might be due to common genetic predispositions.

CDKN2A loss and PIK3CA mutation in myoepithelial-like metaplastic breast cancer.

Metaplastic breast carcinoma comprises a heterogeneous group of tumours with poorly understood pathogenesis. A subset of metaplastic breast cancers show myoepithelial differentiation and constitute a morphological spectrum with ill-defined borders from fibromatosis-like spindle cell carcinoma to myoepithelial carcinoma. In a series of 34 metaplastic breast cancers with spindle cell and myoepithelial differentiation, we found recurrent genetic aberrations, which set them apart from other metaplastic breast cancers and suggest a unique pathogenesis. The majority of cases (28 of 34 patients; 82.4%) showed distinct chromosomal loss in the 9p21.3 region, including CDKN2A and CDKN2B. Biallelic loss of the CDKN2A/B region was found in 50% of deleted cases. Expression of the cyclin-dependent kinase inhibitor CDKN2A (p16) was missing in all samples affected by 9p21.3 loss. Other genomic alterations frequently occurring in triple-negative and metaplastic breast cancer were absent or found in only a minority of cases. Gains of whole chromosome 5 and chromosomal region 5p were observed in nine cases, and were associated with recurrences (p < 0.001). In 64.3% of cases, 9p21.3 loss was accompanied by concurrent PIK3CA mutation. Both genomic abnormalities were also detectable in adenomyoepitheliomas (4/12), which are considered to represent the precursor lesion of myoepithelial metaplastic breast cancer. In adenomyoepithelioma, PIK3CA mutation was present in both luminal epithelial and myoepithelial cells, whereas p16 loss was found only in the latter. We conclude that 9p21.3 (CDKN2A) loss and PIK3CA mutation characterize a subgroup of metaplastic breast cancers with myoepithelial and spindle cell differentiation. Myoepithelial cells in adenomyoepithelioma may show identical aberrations. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Detection of a COVID-19 cluster by universal SARS-CoV-2 testing in a geriatric hospital and implications for infection control management.

Hospital-level COVID-19 testing strategies may require rapid changes depending on the dynamics of local epidemiology. A COVID-19 outbreak in a hospital near the authors' institution, a Geriatric Medicine centre in Berlin, Germany, prompted the implementation of comprehensive SARS-CoV-2 testing. Serial nasopharyngeal swabs were collected from all patients and staff and analysed for SARS-CoV-2 virus RNA using quantitative real-time PCR. In total, 11 of 84 patients (13.1%) and 1 of 147 employees (0.68%) tested positive. Of the 11 positive patients, 9 (81.8%) were asymptomatic at the time of testing. The data were used as the basis for adjusting local COVID-19 containment measures. Only one staff-to-staff transmission was observed, and there was no patient-to-patient, patient-to-staff or staff-to-patient transmission. Three patients infected with SARS-CoV2 died, two deaths being attributable to advanced malignant disease and one to COVID-19-associated myocarditis. In conclusion, universal SARS-CoV-2 testing revealed a cluster of predominantly asymptomatic infections, enabled appropriate local COVID-19 containment decisions and presumably contributed to the prevention of in-hospital SARS-CoV-2 transmission.

[Update 2021: Pulmonary Sequelae of COVID-19 Pneumonia]. / Update 2021: Pulmonale Folgen nach COVID-19-Pneumonie.

Acute COVID-19 pneumonia may result in persistent changes with various imaging and histopathological patterns, including organizing pneumonia and pulmonary fibrosis. In addition, SARS-CoV-2 infection is associated with increased risk of pulmonary vascular endothelialitis and thrombosis. Herein, current findings on pulmonary consequences of COVID-19 with implications for clinical management are summarized based on a selective literature review.

Treatment of disseminated nocardiosis: a host-pathogen approach with adjuvant interferon gamma.

Disseminated nocardiosis is a rare, life-threatening disease. Particularly at risk are immunocompromised patients, highlighting the crucial role of host factors. Conventional intensive antibiotic treatment has improved survival rates, but the overall prognosis of patients with disseminated nocardiosis remains unsatisfactory. In this Grand Round, we present a case of severe nocardiosis that did not respond to standard therapy. The patient's condition deteriorated when antibiotic therapy was given alone and improved substantially only after coadministration of interferon gamma. We review the literature relevant to adjuvant interferon gamma therapy of nocardiosis and discuss its potential harms and benefits. Overall, we consider such treatment as beneficial and low risk if the patient is followed-up closely. We conclude that clinicians should consider this regimen in refractory cases of severe Nocardia infection.

[Post-COVID sequela of the lung - follow up and treatment]. / Post-COVID und die Lunge.

Most people recover completely after an acute infection with the novel corona virus SARS-CoV2. But some people continue to experience symptoms after their recovery. This phenomenon is called post-acute or long-COVID (from week 4 after the infection up to week 12) and persistent post-COVID (symptoms for effects that persist 12 or more weeks after onset). The exact processes that cause long COVID remain unknown.Most of those patients suffer from long-term symptoms of lung damage, including breathlessness, coughing, fatigue and limited ability to exercise. Today, 18 months after the first infections in Europe we have access to the first practical guidelines for the long-/post-COVID syndrome. Further on first prospective studies analysing the incidence of post-COVID are now available.In this review we will discuss some questions about treatment and follow up of patients suffering from pulmonary sequelae after their COVID-19 infection, based on the actual literature.

Impact of a computerized physician order entry (CPOE)-based antibiotic stewardship intervention on the treatment duration for pneumonia and COPD exacerbations.

BACKGROUND: In hospitalized patients, the duration of antibiotic therapy for uncomplicated pneumonia is often longer than recommended in clinical guidelines. Consequences include increased risk of Clostridioides difficile infection and the emergence of antibiotic resistance. Reducing the duration of antibiotic therapy is an important goal of antibiotic stewardship (ABS) programs. OBJECTIVE: To evaluate the impact of a computerized physician order entry (CPOE)-based ABS intervention on treatment duration in respiratory infections and on antibiotic use. METHODS: A new type of prescription tool featuring a "soft stop order" was introduced into the CPOE system in the Respiratory Medicine department of a Thorax Center. The effect of this intervention was evaluated after 24 weeks using a retrospective before-and-after study design. RESULTS: A total of 210 patients were evaluated (preintervention group n = 109, postintervention group n = 101). Mean antibiotic treatment duration decreased from 9.59 days to 7.25 days (p < 0.001). It was reduced from 9.93 to 7.21 days (p < 0.001) in community-acquired pneumonia, 10.21 to 7.81 days (p = 0.05) in hospital-acquired pneumonia and 7.81 to 6.83 days (p = 0.14) in COPD exacerbations. The proportion of patients treated according to clinical guidelines increased from 35.8% to 69.3% (p < 0.001). The mean quarterly antibiotic use density was 41.2 RDD/100 PD (recommended daily doses per 100 patient days) before the intervention and decreased to 34.03 RDD/100 PD after the intervention (p = 0.037). CONCLUSION: Our study demonstrates the short-term effectiveness of a CPOE-based ABS intervention to reduce antibiotic treatment duration for uncomplicated pneumonia. This approach may be particularly suitable for hospitals with limited ABS resources.

[COVID-19: A Pneumological Point of View - Long-Term Sequelae of COVID-19 - Implications For Follow-up In Respiratory Medicine]. / COVID-19 aus Sicht der Pneumologie ­ Langzeitfolgen und Implikationen für die pneumologische Nachsorge.

The long-term sequelae of COVID-19 on are not yet predictable. Radiological and histopathological data on COVID-19 and observational studies after the SARS-CoV-1 pandemic 2003/2004 suggest that in a proportion of COVID-19 patients, functional limitations due to pulmonary fibrosis and other patterns of lung damage may persist. Systematic follow-up, based on prudent pulmonary function testing, is warranted for the correct diagnosis, graduation and treatment of the underlying pathology at an early stage. This review summarizes the potential spectrum of Post-COVID-19 pulmonary disease patterns and provides recommendations for the follow-up care of COVID-19 patients in the field of respiratory medicine.

[Antibiotic Stewardship in Community-Acquired Pneumonia]. / Antibiotic Stewardship bei ambulant erworbener Pneumonie.

Antibiotic stewardship (ABS) denotes structured and continuous measures to improve the quality of prescribing anti-infectives. The aim is to achieve optimal treatment results and to minimize undesirable effects, especially the emergence of antibiotic resistance. This review summarizes the most important ABS principles based on recently published studies with implications for the management of community-acquired pneumonia. Local guidelines, education and training and "prospective audit and feedback" are established strategies to improve the management of patients with community-acquired pneumonia. However, the implementation of ABS programs requires trained personnel and may be impeded by limited structural and time resources. Hence, electronic health records and computer-based interventions are useful support for ABS programs and offer potential to facilitate ABS in inpatient and outpatient care. PCR-based rapid diagnostic tests, PCT-guided algorithms and penicillin allergy testing are suitable procedures to supplement ABS programs.

[Exacerbations of Chronic Obstructive Pulmonary Disease - Diagnostic Approach, Management and Follow-up Care]. / COPD: Umgang mit Exazerbationen ­ Diagnostik, Therapie und Nachsorge.

Exacerbations are major events in the disease process in patients with chronic obstructive pulmonary disease (COPD). They have a negative effect on the quality of life and the progression of the disease. Frequent exacerbations are associated with increased mortality. In addition to the optimal therapy, the prevention of further exacerbations and the attention to concomitant diseases are prognostically crucial for the patients. In this review article, current recommendations for the diagnosis, therapy and follow-up care of COPD exacerbations are summarized.

[Thoracentesis - Step by Step]. / Pleurapunktion ­ Schritt für Schritt.

Pleural effusions of unknown origin and parapneumonic effusions almost invariably require thoracentesis. Fluid analysis is fundamental and guides further diagnostic and therapeutic decisions. Thoracentesis yields high diagnostic value and is a generally safe procedure - given that some basic principles are considered.

Tracheal, laryngeal and pulmonary mucormycosis followed by organizing pneumonia in a patient with Adult Onset Still's Disease.

We report a case of tracheal, laryngeal and pulmonary mucormycosis in a patient receiving immunosuppressive medication for an autoinflammatory fever syndrome. Mucormycosis was confirmed by histopathology from tracheal specimens and molecular evidence of Lichtheimia. A surgical approach was not possible because of the multifocal disease pattern and the extent of tracheal involvement. The patient was successfully treated with liposomal amphotericin B followed by posaconazole maintenance therapy. After 9 months, recurrent pulmonary mucormycosis was suspected but emerged as organizing pneumonia without evidence of active fungal infection.

Prognostic factors in the myoepithelial-like spindle cell type of metaplastic breast cancer.

Metaplastic breast carcinoma (MBC) comprises a heterogeneous group of tumors with difficult to predict biological behavior. A subset of MBC, characterized by spindle-shaped tumor cells with a myoepithelial-like immunophenotype, was entered into a retrospective study (n = 42, median follow-up time 43 months). Molecular parameters (DNA sequences of mutation hot spots in AKT1, ALK, APC, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SF3B1, SMAD4, SRC, SRSF2, STK11, TP53, and U2AF1; copy numbers for EGFR, c-myc, FGFR, PLAG, c-met) were assessed. None of the patients had axillary lymph node involvement. In 13 cases, local recurrence developed after surgery (30.9 %). Distant metastasis occurred in seven patients (17 %; four after local recurrence). The most frequent genetic alteration was PIK3CA mutation (50 % of cases). None of the pathological parameters (size, grade, stage, Ki-67 labeling index) was significantly associated with disease-free survival (DFS) or overall survival (OS). PIK3CA mutation, especially the H1047R type, tended to adversely affect OS. Type of resection (mastectomy vs. breast-conserving therapy, width of margins) or adjuvant radiotherapy had no influence on DFS or OS, whereas in the group treated with radio-/chemotherapy, no local recurrence or metastasis and no death occurred. We conclude that the spindle cell type of MBC with myoepithelial features exhibits a higher frequency of PIK3CA mutation than other types of metaplastic or basal-like breast cancer and may benefit from combined radio-/chemotherapy. Classical pathological parameters are not helpful in identifying the high-risk tumors among this subgroup of MBC.