[Statement of the Austrian Society of Pneumology (ASP)]. / Stellungnahme der Österreichischen Gesellschaft für Pneumologie (ÖGP): Management von Patienten mit SARS-CoV-2-Infektionen und von Patienten mit chronischen Lungenerkrankungen während der COVID-19-Pandemie (Stand 27.04.2020).

The COVID-19 pandemic is currently a challenge worldwide. In Austria, a crisis within the health care system has so far been avoided. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV­2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic. However, COVID-19-specific adjustments are useful. The treatment of patients with chronic lung diseases must be adapted during the pandemic, but must still be guaranteed.

Cigarette smoking and culture conversion in patients with susceptible and M/XDR-TB.

BACKGROUND: Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Active cigarette smoking may have a significant impact on treatment responses to anti-tuberculosis treatment. OBJECTIVE: To ascertain the effect of smoking on Mycobacterium tuberculosis sputum culture conversion rates following treatment initiation in patients with susceptible, multidrug-resistant and extensively drug-resistant TB (M/XDR-TB). METHOD: Sputum cultures of smoking and non-smoking patients with pulmonary TB (PTB) treated at a referral centre in Germany were evaluated. RESULTS: Between January 2012 and March 2017, 247 patients with PTB treated at the Medical Clinic of Research Center Borstel, Borstel, Germany, were included in the study. Of 247 patients, 65 (26.3%) were infected with multidrug-resistant strains of M. tuberculosis (MDR-TB). Sputum culture examinations were performed on a weekly basis. Active smoking (n = 111; time to culture conversion [TCC] 50.7 days, interquartile range [IQR] 26.5-73.0) and former smoking (n = 72; TCC 43.1 days, IQR 19.8-56.0) significantly delayed culture conversion rates (P < 0.001) when compared with never smoking (n = 64; TCC 33.2 days, IQR 8.0-50.3). Delay in TCC among smoking, non-MDR-TB patients (n = 138; TCC 47.3 days, IQR 19.0-89.0) was comparable with non-smoking, MDR-TB patients (n = 20; TCC 53.0 days, IQR 18.0-71.0). The shortest TCC was observed in non-smoking, non-MDR-TB patients (n = 44; TCC 33.0 days, IQR 10.0-48.5), whereas the longest was seen in smoking, MDR-TB patients (n = 45; TCC 60.7 days, IQR 33.3-89.0); P < 0.001). CONCLUSION: Active cigarette smoking and, to a lesser extent, former cigarette smoking, substantially delayed culture conversion in PTB.

Treatment responses in multidrug-resistant tuberculosis in Germany.

BACKGROUND: Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. OBJECTIVE: To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. METHOD: Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany. Treatment was conducted following current guidelines and individualised on the basis of drug susceptibility testing. Two-month and 6-month sputum smear and sputum culture conversion rates were assessed. A clinical and radiological score were used to assess response to anti-tuberculosis treatment. RESULTS: Non-M/XDR-TB (n = 29) and M/XDR-TB (n = 46) patients showed similar rates of microbiological conversion: 2-month smear conversion rate, 90% vs. 78%; culture conversion rate, 67% vs. 61%; time to smear conversion, 19 days (IQR 10-32) vs. 31 days (IQR 14-56) (P = 0.066); time to culture conversion, 39 days (IQR 17-67) vs. 39 days (IQR 6-85) (P = 0.191). Both clinical and radiological scores decreased after the introduction of anti-tuberculosis treatment. CONCLUSION: There were no significant differences in scores between the two groups until 6 months of treatment. Under optimal clinical conditions, with the availability of novel diagnostics and a wide range of therapeutic options for individualised treatment, patients with M/XDR-TB achieved 6-month culture conversion rates that were compatible with those in patients with non-M/XDR-TB.

[Aspergillus in airway material : Ignore or treat?] / Aspergillus-Nachweis im Atemwegsmaterial : Ignorieren oder behandeln?

Fungi of the genus Aspergillus are ubiquitously present. Even though humans inhale Aspergillus spores daily under natural conditions, Aspergillus-associated pulmonary diseases only occur under special circumstances. Whether an Aspergillus-associated disease develops and which type of Aspergillus-associated disease develops depends on the constitution of the host. The spectrum of Aspergillus-associated pulmonary diseases ranges from allergic diseases, such as hypersensitivity pneumonitis to allergic infectious diseases, such as allergic bronchopulmonary aspergillosis (ABPA) and bronchocentric granulomatosis (BG) to infectious diseases, such as invasive (IA) or semi-invasive aspergillosis (SIA) and chronic pulmonary aspergillosis (CPA). Identification of Aspergillus spp. from sputum or bronchopulmonary secretions is not sufficient for a definitive diagnosis of Aspergillus-associated infections. The gold standard is the identification of Aspergillus spp. from lung tissue by culture or by histopathological methods; however, in clinical practice the decision to initiate antifungal therapy is more often based on immunological methods, such as the detection of Aspergillus-specific IgG antibodies from peripheral blood or galactomannan antigens from bronchoalveolar lavages. Acute IA or SIA infections have a high mortality and require immediate antifungal therapy. With rare exceptions CPA cannot be cured by medicinal therapy alone; however, active CPA can be brought into remission with antifungal therapy. Eradication of Aspergillus in CPA can as a rule only be successful using a combined antimycotic and surgical intervention.

[A 73-year-old female patient after liver and kidney transplantation with dull pain in the epigastrium and recurrent epistaxis]. / 73-jährige leber- und nierentransplantierte Patientin mit dumpfen Oberbauchschmerzen und rezidivierendem Nasenbluten.

A 73-year-old female patient who had received a liver and kidney transplantation presented with symptomatic pancytopenia and right-sided upper abdominal pain. The histological investigation of a bone marrow biopsy showed the extremely rare manifestation of a disseminated Merkel cell carcinoma with infiltration of the bone marrow and suppression of hematopoiesis. Also a Coombs test positive hemolytic anemia did not show a significant response to high-dose steroid therapy. Palliative chemotherapy with carboplatin and etoposide at reduced dosage had to be terminated due to deterioration of the patient's general condition. The patient died 2 days after initiation of chemotherapy.

Interobserver agreement and accuracy of non-invasive diagnosis of endometriosis by transvaginal sonography.

OBJECTIVES: To evaluate interobserver agreement and accuracy of transvaginal sonography (TVS) in diagnosing deep infiltrating endometriosis (DIE) and endometriomas. METHODS: A total of 67 consecutive patients referred to a pelvic pain clinic and scheduled for laparoscopy were enrolled in the study between January 2013 and January 2014. Patients were independently examined prospectively by two experienced sonographers (Observers A and B) who were blinded to the other's results. For the two observers, Gwet's first-order agreement coefficient (Gwet's AC1) was used to calculate interobserver agreement and diagnostic accuracy, as well as sensitivity, specificity, positive (PPV) and negative (NPV) predictive values using TVS, as compared to laparoscopy, for diagnosing DIE and endometriomas. RESULTS: Among the 67 patients enrolled, 65 were analyzed. For the diagnosis of DIE and endometriomas by TVS, the level of agreement (Gwet's AC1) between Observers A and B and sensitivity/specificity values for the respective Observers were, by site: vagina (Gwet's AC1, 0.933; 62%/94% and 82%/94%), bladder (Gwet's AC1, 1.00; 67%/97% and 67%/97%), uterosacral ligaments (Gwet's AC1, 0.84; 73%/83% and 53%/90%), adnexa (Gwet's AC1, 0.95; 71%/93% and 71%/93%), rectovaginal septum (Gwet's AC1, 0.95; 40%/90% and 33%/87%) and rectosigmoid (Gwet's AC1, 0.98; 93%/96% and 94%/98%) which reflected high interobserver agreement. With the exception of sensitivity of diagnosis of DIE affecting the RVS, similar results were observed when TVS was compared with laparoscopy. CONCLUSIONS: TVS is a highly accurate and reproducible method for non-invasive diagnosis of DIE by well-trained professionals.

Dyspareunia and quality of sex life after surgical excision of endometriosis: a systematic review.

Dyspareunia, a common symptom of endometriosis, severely affects quality of sex life in affected women. The objective of the present work was to review the effect of surgical resection of endometriosis on pain intensity and quality of sex life. MEDLINE and EMBASE databases were searched for papers investigating the outcome after surgical endometriosis resection on dyspareunia and quality of sex life measured via VAS/NAS respectively via standardised measuring instruments. Data did not permit a meaningful meta-analysis. Out of 64 papers, three studies fulfilled the predefined inclusion criteria involving 128 patients with endometriosis and dyspareunia preoperatively. All included studies showed a significant postoperative reduction (p<0.05) of dyspareunia after a follow-up period of 12 up to 60 months. Sex life also improved significantly (p<0.05), and predominantly evaluated parameters like quality of life and mental health. Intra- and postoperative complications were described in two out of three studies. Surgical excision of deep infiltrating endometriosis is feasible and improves dyspareunia and quality of sex life significantly.

Which lumen is the source of catheter-related bloodstream infection in patients with multi-lumen central venous catheters?

PURPOSE: Paired blood cultures, drawn from the catheter and a peripheral vein, used for calculation of the differential time to positivity (DTP), have been proposed for the detection of catheter-related bloodstream infections (CRBSIs). The most relevant catheter lumen to be sampled in multi-lumen central venous catheters (CVCs) has not been recommended. METHODS: Forty-four febrile neutropaenic patients, following haematopoietic stem cell transplantation (HSCT) and with multi-lumen CVCs in place, were investigated using the DTP method of blood samples drawn from every lumen of the CVC and a peripheral vein. RESULTS: Twelve of 44 patients (27 %) had CRBSIs, as determined by the DTP method. In 10 of 12 (83 %) febrile neutropaenic patients, after HSCT, CRBSIs originated from the CVC lumen used for parenteral nutrition and blood products only. 17 % had CRBSI originating from the other CVC lumen (p = 0.039). CONCLUSION: In most patients, CRBSIs originated from the CVC lumen used for parenteral nutrition and blood products, indicating that this lumen is the main source of CRBSI. However, since 17 % of patients had CRBSIs originating from another lumen, each lumen of multi-lumen CVCs has to be considered as a potential source of CRBSI and should, ideally, be sampled in order to avoid failure in diagnostic procedures.

Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.

STUDY QUESTION: What is the length of the diagnostic delay for endometriosis in Austria and Germany, and what are the reasons for the delay? SUMMARY ANSWER: The diagnostic delay for endometriosis in Austria and Germany is surprisingly long, due to both medical and psychosocial reasons. WHAT IS KNOWN ALREADY: Diagnostic delay of endometriosis is a problematic phenomenon which has been evaluated in several European countries and in the USA, but has not been reported for Germany and Austria. STUDY DESIGN, SIZE, DURATION: A cross-sectional, questionnaire-based multicentre study was conducted in tertiary referral centers in Austria and Germany. From September 2010 to February 2012, 171 patients with histologically confirmed endometriosis were included. PARTICIPANTS, SETTING, METHODS: Patients with a previous history of surgically proven endometriosis, internal diseases such as rheumatic disorders, pain symptoms of other origin, gynecological malignancy or post-menopausal status were excluded from the analysis. Patients with histologically confirmed endometriosis completed a questionnaire about their psychosocial and clinical characteristics and experiences. Of 173 patients, two did not provide informed consent and were excluded from the study. MAIN RESULTS AND THE ROLE OF CHANCE: The median interval from the first onset of symptoms to diagnosis was 10.4 (SD: 7.9) years, and 74% of patients received at least one false diagnosis. Factors such as misdiagnosis, mothers considering menstruation as a negative event and normalization of dysmenorrhea by patients significantly prolonged the diagnostic delay. No association was found between either superficial and deep infiltrating endometriosis or oral contraceptive use and the prolongation of diagnosis. LIMITATIONS AND REASONS FOR CAUTION: There was a possible selection bias due to inclusion of surgically treated patients only. WIDER IMPLICATIONS OF THE FINDINGS: Several factors causing prolongation of diagnosis of endometriosis have been reported to date. The principal factors observed in the present study are false diagnosis and normalization of symptoms. Teaching programs for doctors and public awareness campaigns might reduce diagnostic delay in Central Europe. STUDY FUNDING/COMPETING INTEREST(S): No competing interests exist.

Emergence of carbapenem-resistant Enterobacteriaceae in Austria, 2001-2010.

We report the emergence of carbapenem-resistant Enterobacteriaceae in Austria. Over a 10-year period, carbapenem-resistant Enterobacteriaceae isolates were obtained from 13 hospitalized patients, with the first isolation in the year 2005 and a remarkable increase in the number of involved patients in 2010. Carbapenem-resistant Enterobacteriaceae comprise eight Klebsiella pneumoniae isolates, four Klebsiella oxytoca isolates, and one Escherichia coli isolate. The detected carbapenemases were the metallo-ß-lactamases New Delhi ß-lactamase, VIM and IMP, and the serin-ß-lactamase Klebsiella pneumoniae carbapenemase.

Comparison of fluorescence in situ hybridisation using peptide nucleic acid probes, Gram stain/acridine orange leukocyte cytospin and differential time to positivity methods for detection of catheter-related bloodstream infection in patients after haematopoietic stem cell transplantation.

In 46 febrile neutropenic patients who had undergone haematopoietic stem cell transplantation, the fluorescence in situ hybridisation using peptide nucleic acid probes (PNA FISH), Gram stain/acridine orange leukocyte cytospin (Gram/AOLC), and differential time to positivity (DTP) methods were performed for detection of catheter-related bloodstream infections (CRBSIs). As compared with the DTP method (which detected 11 patients with CRBSI), the PNA FISH and the Gram/AOLC methods detected ten of 11 CRBSI patients, resulting in a sensitivity, specificity, negative predictive value and positive predictive value of 91%, 100%, 97% and 100%, respectively, for the PNA FISH method as well as for the Gram/AOLC method.

Relationship between carnitine, fatty acids and insulin resistance.

Increased plasma free fatty acid (FFA) levels are a feature of insulin resistance and type 2 diabetes. The aim of the present study was to assess the effect of L-carnitine supplementation on plasma lipids and the expression of enzymes in peripheral mononucleated cells (PMNC) involved in the regulation of fatty acid and glucose oxidation. L-Carnitine supplementation of 2 g/day resulted in a significant decrease in plasma FFA and in a less pronounced diminution of the plasma triacylglycerols. In addition, a concomitant increase in the relative mRNA abundances of carnitine acyltransferases (5- to 10-fold) and of the carnitine carrier OCTN2 (12-fold) in PMNC of pregnant women was found. The results of the present study provide evidence that L-carnitine supplementation in pregnancy (2 g/day) avoids a striking increase in plasma FFA, which are thought to be the main cause of insulin resistance and consequently gestational diabetes mellitus.

Ifosfamide/mesna as salvage therapy in platinum pretreated ovarian cancer patients--long-term results of a phase II study.

PURPOSE: Salvage chemotherapy in advanced ovarian cancer is not yet standardized. PATIENTS: Twenty-one consecutive patients progressing on or relapsing after previous platinum-containing treatment were eligible for treatment with ifosfamide 5 g/m(2) infused over a 24-hour period every 3 weeks in a Phase II trial. After an initial bolus of 1 g/m(2) of mesna, mesna was applied at a dosage of 5 g/m(2) concomitantly with ifosfamide followed by additional dosages of 200 mg 3 times at 4-hour intervals after termination of the ifosfamide infusion. RESULTS: The rate of objective responses was 19 percent, with a 95%CI [5.45-41.91 percent]. One patient achieved a pathologic complete remission (pCR) and 3 patients a clinical partial remission (PR). Median time-to-progression was 3 months. One patient was a long-term survivor. Main toxicities according to NCI-CTC included Grade 4 neurotoxicity in one patient, Grade 3 gastrointestinal toxicity in 5 patients, Grade 3 infection in one patient, and Grade 3 and 4 leucopenia in 6 and 2 patients, respectively. CONCLUSIONS: Monotherapy with ifosfamide represents an active regimen for salvage chemotherapy in advanced ovarian cancer patients progressing on or relapsing after previous platinum-pretreatment, even yielding a long-term surivor.

Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients. 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin.

This prospective multicentre phase III trial was conducted to assess whether increased platinum dose intensity (DI) by combining carboplatin with cisplatin has an impact on overall survival (OS) and progression-free interval (PFI) compared with the standard combination of cyclophosphamide and cisplatin in patients with epithelial ovarian cancer. A total of 253 patients with epithelial ovarian cancer of stages International Federation of Gynecology and Obstetrics (FIGO) IC-IV were randomised to receive either cyclophosphamide (600 mg/m(2), intravenously (i.v.), day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=125) as the standard regimen or carboplatin (300 mg/m(2), i.v., day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=128), every 28 days for six courses. The median follow-up was 6.0 years. 124 patients randomised to the platinum dose-intensified arm and 123 patients randomised to the standard arm met all of the eligibility criteria. Patient characteristics were well balanced between the two treatment groups. All eligible patients randomised were included in the analysis of OS and PFI. The median OS of the standard and platinum dose-intensified arms were 41.2 (95% Confidence Interval (CI): 29.2-50.7) and 43.0 months (95% CI: 34.3-63.2), respectively (P=Non-significant (N.S.). The median PFI in the standard arm was 29.7 (95% CI: 17.4-41.7) versus 23.1 months (95% CI: 17.8-35.4) in the platinum dose-intensified arm, respectively (P=N.S.). Toxicity, comprising leucopenia, granulocytopenia, thrombocytopenia, anaemia, emesis and nausea, was statistically significantly higher in the platinum dose-intensified arm than in the standard arm. Unexpectedly, no statistically significant differences were found between the 2 arms' overall neuro- and ototoxicity. When converting carboplatin-platinum into cisplatin-platinum on the basis of an equivalence ratio of 4:1, patients in the platinum dose-intensified arm received a total platinum dose 1.58 times the platinum dose of the standard arm. With 35.0 mg/m(2)/week being administered, the total platinum DI of the dose-intensified arm was statistically significantly (P<0.0001) higher than that of the standard regimen (with 22.0 mg/m(2) being administered). Calculating the average administered relative dose intensities of the regimens yielded almost identical results with 0.56 and 0.58 for the standard and experimental arms, respectively. Thus, by conventional means, a 1.6-fold increase in the platinum DI could be reached by combining carboplatin and cisplatin without unacceptable morbidity. Nevertheless, this did not translate into any therapeutic benefit for the patient, even in the optimally debulked group of patients for whom dose-intensification would have been expected to be of benefit.

Sentinel lymph node detection with large human serum albumin colloid particles in breast cancer.

Detection of metastatic involvement of lymph nodes is essential for management and prognostic evaluation in breast cancer patients. The success of lymphatic mapping depends on identifying the sentinel lymph node(s) draining the primary tumour. However, when mapping is performed with a radiocolloidal agent, the number of hot lymph nodes varies with the agent and its size, among other factors. In this study, we evaluated prospectively the detection rate of sentinel lymph nodes in breast cancer when injecting large particles (100-600 nm) of human serum albumin colloids (Senti-Scint). In 128 consecutive breast cancer patients without palpable lymph nodes, pre-operative static lymphoscintigraphic mapping of the breast was performed after subcutaneous injection of 15 MBq of the radiocolloid. Lymphoscintigrahic results were compared with intra-operative surgical gamma detection probe and blue dye mapping data. Pre-operative lymphoscintigraphy and surgical gamma detection probe both correctly detected 203 sentinel lymph nodes in 122/128 patients (95%), while blue dye mapping showed only 183 sentinel lymph nodes in 82% of the patients. Only one or two sentinel lymph nodes were identified in each patient, which allowed the surgeon easily to find the sentinel lymph node(s) intra-operatively. In conclusion, lymphoscintigraphy with large particles of human serum albumin colloids is a helpful and reliable procedure for the surgical management of breast cancer.

Cross-linked type I collagen C- and N-telopeptides in women with bone metastases from breast cancer.

This study documents values of biochemical markers of bone remodeling in 106 patients with breast cancer. Based on scintigraphic and radiological findings, patients were divided into 3 groups: 19 patients with bone metastases, 65 patients without bone metastases and normal bone scintigrams, and 22 patients with pathological, non-malignant findings on scintigraphy without proof of bone metastases. Urinary cross-linked type I collagen N-telopeptides (NTx) and serum cross-linked type I collagen C-telopeptides (ICTP) were assessed as markers of bone resorption. Bone alkaline phosphatase (BAP) was assessed as a marker of bone formation. All three markers were significantly higher in patients with bone metastases compared to both patients without skeletal recurrence and those with pathological, non-malignant scintigraphic findings (p < 0.01). There were no statistically significant differences between the latter two groups. The clinical sensitivity for diagnosing bone metastases was 44% for NTx, 65% for ICTP, and 26% for BAP, respectively. The clinical specificitiy for discriminating patients with bone disease from those without were 79%, 91%, and 92% for NTx, ICTP, and BAP, respectively. In conclusion, markers of bone remodeling are increased in patients with breast cancer metastatic to the skeleton. The sensitivity of the markers presented in this paper did not seem to be sufficient enough for early identification of patients with subclinical bone recurrence in a clinical practice setting.

Scintimammography enhances negative predictive value of non-invasive pre-operative assessment of breast lesions.

AIMS: The aim of this study was to develop a criterion with a high negative predictive value for the evaluation of breast lesions. We aimed to determine the value of combining three non-invasive tests, mammography (MM), ultrasonography (USS) and 99mTc-methoxyisobutylisonitrite (99mTc-MIBI) scintimammography (scinti-MM). METHODS: We included 94 consecutive patients with suspected lesions detected by mammography or on physical examination. MM, USS and scinti-MM were performed no more than 4 weeks prior to excisional biopsy in all patients. We then compared the biopsy results with a score calculated for each patient, derived from the results of the three tests, which we termed 'mamma malignancy index' (MMI). RESULTS: Each of the three exams yielded a score ranging from 0 to 2, with 0 representing an almost certainly benign lesion, 1 an indeterminate finding and 2 a likely malignant lesion, and hence giving a total score ranging from 0 to 6. The biopsy results showed that the lesions in 64 patients were benign. Forty-nine (77%) of these patients had received an MMI score of 0 or 1. The negative predictive value for malignancy in patients with a score less than 2 was 100%. CONCLUSIONS: Since the smallest detected lesion was 9 mm in diameter, we conclude that MMI may be a highly useful diagnostic tool in the delineation of breast lesions > or =1 cm which should not be routinely referred for biopsy but may be followed non-invasively. Although fine needle aspiration has limitations, we would recommend it as a less invasive method to evaluate suspected lesions smaller than 1 cm.