A case of fulminant respiratory diphtheria in a 24-year-old Afghan refugee in Austria in May 2022: a case report.

PURPOSE: Raising awareness of respiratory diphtheria and for the importance of early antitoxin administration. METHODS: Report of a case of fulminant, imported respiratory diphtheria in an otherwise healthy 24-year-old Afghan refugee in Austria in May 2022. RESULT: This was the first case of respiratory diphtheria in Austria since 1993. Diphtheria antitoxin was administered at an already progressed disease stage. This delay contributed to a fulminant disease course with multiorgan failure and death. CONCLUSION: In high-income countries with low case numbers, awareness of respiratory diphtheria and for the importance of early antitoxin administration must be raised.

Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19-Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT).

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed. Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials. Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].

Gender differences and influenza-associated mortality in hospitalized influenza A patients during the 2018/19 season.

BACKGROUND: In this study we analyzed gender differences in the clinical presentation of patients with molecular confirmed influenza A. Additionally, we tried to identify predictors of influenza-associated mortality. MATERIALS/METHODS: In this prospective observational multi-center-study we included all influenza-positive patients ≥ 18 years who were hospitalized and treated on flu-isolation-wards in three hospitals in Vienna during the 2018/19 influenza season. Diagnoses were made via Cobas® Liat® POCT. RESULTS: 490 Patients (48.8% female) tested positive for influenza A. Female patients were older (median age 76 years vs. 70 years, p < 0.001). Male patients had a higher rate of chronic liver disease in history (8.8% vs. 2.9%, p = 0.006), myositis (11.7% vs. 3.1%, p < 0.001) and ICU admissions (9.6% vs. 4.6%, p = 0.03). The in-hospital mortality rate was 4.3% and increased to 9.5% during the 90-day follow-up period. Female patients > 75 years had a significantly higher in-hospital mortality rate than ≤ 75-year-old females (9.2% vs. 1.7%, p = 0.019). This effect was not observed in male patients (5.4% vs. 1.9%, p = ns). Age > 75 years (OR 5.49, 95% CI 1.10-27.43), acute heart failure (OR 3.56, 95% CI 1.03-12.05) and ICU admission (OR 6.1, 95% CI 0.98-37.91) were predictors for in-hospital mortality for female patients, while any malignancy (OR 9.4, 95% CI 1.90-46.54) and ICU admission (OR 7.05, 95% CI 1.44-34.55) were predictors in male patients. CONCLUSIONS: Gender is associated with differences in clinical presentation and complications of influenza A virus infection. Women with acute heart failure or aged > 75 years have an increased risk of influenza associated in-hospital mortality, while ICU admission and any malignancy are predictors for male patients. Mortality rates in patients > 75 years are 5-10 times higher compared to their non-hospitalized influenza-negative Austrian counterparts.

An approach to lifting self-isolation for health care workers with prolonged shedding of SARS-CoV-2 RNA.

PURPOSE: According to the European Public Health Authority guidance for ending isolation in the context of COVID-19, a convalescent healthcare worker (HCW) can end their isolation at home and resume work upon clinical improvement and two negative RT-PCR tests from respiratory specimens obtained at 24-h intervals at least 8 days after the onset of symptoms. However, convalescent HCWs may shed SARS-CoV-2 viral RNA for prolonged periods. METHODS: 40 healthy HCWs off work because of ongoing positive RT-PCR results in combined nasopharyngeal (NP) and oropharyngeal (OP) swabs following SARS-CoV-2 infection were invited to participate in this study. These HCWs had been in self-isolation because of a PCR-confirmed SARS-CoV-2 infection. NP and OP swabs as well as a blood sample were collected from each participant. RT-PCR and virus isolation was performed with each swab sample and serum neutralization test as well as two different ELISA tests were performed on all serum samples. RESULTS: No viable virions could be detected in any of 29 nasopharyngeal and 29 oropharyngeal swabs taken from 15 long-time carriers. We found SARSCoV- 2 RNA in 14/29 nasopharyngeal and 10/29 oropharyngeal swabs obtained from screening 15 HCWs with previous COVID-19 up to 55 days after symptom onset. Six (40%) of the 15 initially positive HCWs converted to negative and later reverted to positive again according to their medical records. All but one HCW, a healthy volunteer banned from work, showed the presence of neutralizing antibodies in concomitantly taken blood samples. Late threshold cycle (Ct) values in RT-PCR [mean 37.4; median 37.3; range 30.8-41.7] and the lack of virus growth in cell culture indicate that despite the positive PCR results no infectivity remained. CONCLUSION: We recommend lifting isolation if the RT-PCR Ct-value of a naso- or oropharyngeal swab sample is over 30. Positive results obtained from genes targeted with Ct-values > 30 correspond to non-viable/noninfectious particles that are still detected by RT-PCR. In case of Ct-values lower than 30, a blood sample from the patient should be tested for the presence of neutralizing antibodies. If positive, non-infectiousness can also be assumed.

Late onset pulmonary embolism in young male otherwise healthy COVID-19 patients.

SARS-CoV-2 infection is associated with increased risk of thrombosis in severely ill patients but little is known about the risk in outpatients with mild to moderate disease. Our case series consists of four male otherwise healthy patients between 32 and 50 years of age. Initial symptoms completely resolved but they developed new onset of dyspnea and thoracic pain at days 14 to 26. CT scan revealed pulmonary embolism in all patients which led to hospitalization. Standard anticoagulation practice needs to be re-evaluated and may  be considered for certain outpatients with COVID-19.

Successful management of the first reported case in Austria of COVID-19 with ARDS.

We report the successful management of a patient with severe respiratory failure due to COVID-19 admitted to an intensive care unit complicated by secondary catheter-related infection of Candida glabrata. We are discussing some of the clinical challenges and the pitfalls in molecular diagnosis of SARS-CoV-2, including the fact that a positive PCR result may not always reflect infectiousness.

Microwave de-/anti-icing using the midas-technology.

For aviation, a suitable alternative for currently used in-flight anti-/de-icing technologies for today's aircrafts with metal structures and future aircrafts with replaced composite structures is necessary. Intense investigations performed at FZK have been together in collaboration with aircraft manufacturers to design and develop a new avionic microwave technology for monolithic composite structures.The full system integration has been evaluated for several airplanes considering the structural and efficiency demands. The concept of this MIDAS (MIcrowave De-icing Anti-icing System) technology as well their recent results will be presented. A full system integration has been tested and is visualized in the paper.

Computer simulation for ergonomic improvements in laparoscopic surgery.

It is the aim of this study to reduce the stress and strain of the medical staff during laparoscopic operations, and, simultaneously, to increase the safety and efficiency of an integrated operation room (OR) by an ergonomic redesign. This was attempted by a computer simulation approach using free modelling of the OR and 3D human models (manikins). After defining ergonomically "ideal" postures, optimal solutions for key elements of an ergonomic design of the OR (position and height of the image displays, height of the OR table and the Mayo stand) could be evaluated with special regard to the different individual body size of each member of the team. These data should be useful for the development of team adapted, user friendly integrated OR suites of the future.

Ergonomic assessment of the static stress confronted by surgeons during laparoscopic cholecystectomy.

BACKGROUND: Only a few reports on static strain in the spine, neck, and head of the surgeon are available, describing it as "distinctly harmful." The aim of this study was to objectively prove the static burden during laparoscopic operations. For this, new industrial software called PCMAN was used, capable of measuring and comparing the postures of the surgeon at different monitor placements. METHODS: Two simultaneous and synchronized video recordings of laparoscopic cholecystectomies (LC) were done using miniDV digital camcorders with the cameras standing at a 90 degrees angle to each other. Twenty operations were performed using two different placements of the monitor. In 10 cases, the monitor was placed at the patient's head in the center, and in 10 cases at the left side of the patient. Using the time codes of the recordings, different steps of the operation were identified, and the duration of these measured in seconds. Very characteristic, longer lasting postures were imported to and analyzed with the software. Results of the different setups were compared to each other, and to an "ideal" comfort posture. RESULTS: During the intermediate steps of the operations the rate of static phases is significantly higher. Measuring the typical postures of these phases the trunk and head are significantly more rotated and bent than in comfort positions. When the monitor was at the side of the patient facing the surgeon, results were closer to the comfort posture. CONCLUSIONS: It was proven that surgeons are confronted by significant static burden during LC. The software used was able to evaluate objectively the static posture of the surgeon during series of LC. Results also confirmed that the position of monitors significantly influences the surgeon's posture. Best setups for the whole team can be achieved by adjustable multiple monitor systems.

Renal cortical calcification in syngeneic intact rats and those receiving an infrarenal thoracic aortic graft: possible etiological roles of endothelin, nitrate and minerals, and different preventive effects of long-term oral treatment with magnesium, citrate and alkali-containing preparations.

Renal cortical nephrocalcinosis (C-NC) is a rare disorder of uncertain etiology. Using highly inbred (syngeneic) male Lewis rats, we describe the spontaneous occurrence of histologically detectable C-NC in sham operated control rats (Sham; n=12), its aggravation following grafting of the ascending thoracic aorta from a donor rat to the infrarenal aorta of a recipient (ATx; n=12), and differences in C-NC inhibition after 12 weeks of oral administration of magnesium (Mg), citrate and alkali. C-NC is characterized by Kossa-positive areas located in cells of the proximal tubule close to blood vessels and also, to a lesser extent, within glomeruli. After ATx there was vascular overproduction of endothelin (ET-1) but decreased production of nitrate; in renal cortical tissue there was an excess of calcium over Mg and phosphorus and oxalate over citrate. In plasma there was an increase in calcium and creatinine within the normal range. Calcification of tubular cells was eliminated by a preparation containing potassium, sodium and bases (from citrate degradation and bicarbonate) in addition to Mg. Less effective than the latter was Mg-potassium citrate and least effective, Mg citrate. The former treatment also normalized calcemia and urinary nitrate, but only incompletely suppressed ET-1 and had no significant effect on glomerular calcification or tissue and urinary oxalate. Urinary ET-1 excess appeared directly related to the cortical tissue calcium/Mg ratio, and urinary excretion of Mg, citrate and total protein appeared to be inversely related to the severity of C-NC. It was concluded that (1) the highly inbred rat is prone to precipitation of calcium phosphate in the renal cortex; (2) this type of C-NC occurs in close proximity to and within renal vascular tissue and is associated with an imbalance of vasoconstrictors and vasodilators of endothelial origin; (3) effective inhibition of C-NC can be achieved by an alkalinizing combination of Mg, potassium, sodium and citrate, underscoring its utility in the prophylaxis of pathological calcium phosphate deposition. The significance of these findings for the etiology and treatment of clinical disorders with renal and vascular calcification is uncertain and requires further investigation.

Y chromosomal short tandem repeat (STR) loci in a representative group of males living in South Württemberg: a database for application in forensic medicine.

In this study, we resolved the allelic distribution of three Y chromosomal short tandem repeats (STRs), DYS19 (n=218), DYS390 (n=257) and DYS393 (n=215), in a population study of 257 unrelated men living in the area of South Wüerttemberg/Hohenzollern. In DYS19 and in DYS393, five different alleles were discovered, and in DYS390, six different alleles. Forty-nine different haplotypes were found in 202 unrelated male individuals. By investigating each of the three STR systems separately, the most powerful results were found in DYS390, with a PE (power of exclusion) of 0.74, followed by DYS19 (PE: 0.65) and DYS393 (PE: 0.47). Using a combination of two systems (n=202), the PEs ranged from 0.79 (DYS19 and DYS393) to 0.89 (DYS19 and DYS390). The combination of all three STR systems revealed a PE of 0.93.

Linker insertion mutagenesis based on IS21 transposition: isolation of an AMP-insensitive variant of catabolic ornithine carbamoyltransferase from Pseudomonas aeruginosa.

The bacterial insertion sequence IS21 when repeated in tandem efficiently promotes non-replicative cointegrate formation in Escherichia coli. An IS21-IS21 junction region which had been engineered to contain unique SalI and BglII sites close to the IS21 termini was not affected in the ability to form cointegrates with target plasmids. Based on this finding, a novel procedure of random linker insertion mutagenesis was devised. Suicide plasmids containing the engineered junction region (pME5 and pME6) formed cointegrates with target plasmids in an E.coli host strain expressing the IS21 transposition proteins in trans. Cointegrates were resolved in vitro by restriction with SalI or BglII and ligation; thus, insertions of four or 11 codons, respectively, were created in the target DNA, practically at random. The cloned Pseudomonas aeruginosa arcB gene encoding catabolic ornithine carbamoyltransferase was used as a target. Of 20 different four-codon insertions in arcB, 11 inactivated the enzyme. Among the remaining nine insertion mutants which retained enzyme activity, three enzyme variants had reduced affinity for the substrate ornithine and one had lost recognition of the allosteric activator AMP. The linker insertions obtained illustrate the usefulness of the method in the analysis of structure-function relationships of proteins.

The euthanasia debate.

Nurses are key players in determining outcomes for nursing and patient care. They treat patients with actual or potential health problems, act as advocates, and educate patients and families. This makes them eminently qualified to become active participants in the debate as to the legalization of euthanasia.

Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP.

Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module.

Cointegrase, a naturally occurring, truncated form of IS21 transposase, catalyzes replicon fusion rather than simple insertion of IS21.

The bacterial insertion sequence IS21 contains two genes, istA and istB, which are organized as an operon. IS21 spontaneously forms tandem repeats designated (IS21)2. Plasmids carrying (IS21)2 react efficiently with other replicons, producing cointegrates via a cut-and-paste mechanism. Here we show that transposition of a single IS21 element (simple insertion) and cointegrate formation involving (IS21)2 result from two distinct non-replicative pathways, which are essentially due to two differentiated IstA proteins, transposase and cointegrase. In Escherichia coli, transposase was characterized as the full-length, 46 kDa product of the istA gene, whereas the 45 kDa cointegrase was expressed, in-frame, from a natural internal translation start of istA. The istB gene, which could be experimentally disconnected from istA, provided a helper protein that strongly stimulated the transposase and cointegrase-driven reactions. Site-directed mutagenesis was used to express either cointegrase or transposase from the istA gene. Cointegrase promoted replicon fusion at high frequencies by acting on IS21 ends which were linked by 2, 3, or 4 bp junction sequences in (IS21)2. By contrast, cointegrase poorly catalyzed simple insertion of IS21 elements. Transposase had intermediate, uniform activity in both pathways. The ability of transposase to synapse two widely spaced IS21 ends may reside in the eight N-terminal amino acid residues which are absent from cointegrase. Given the 2 or 3 bp spacing in naturally occurring IS21 tandems and the specialization of cointegrase, the fulminant spread of IS21 via cointegration can now be understood.

Occupational risk of Mycobacterium tuberculosis infection in hospital workers.

We conducted a 4-year (1/89-12/92) retrospective cohort study among employees at a large metropolitan hospital where a nosocomial outbreak of multidrug-resistant tuberculosis (TB) had occurred. We compared the risk of tuberculin skin test (TST) conversion among employees who worked on wards where patients with culture-confirmed TB were cared for ("exposed") with the risk among employees who worked on wards with no such patients ("unexposed"). Exposed employees had a higher 4-year risk of TST conversion (14.5%) than unexposed employees (1.4%) (adjusted relative risk 13.4; 95 percent confidence interval 5.1-35.2). Exposed employees had significantly higher risks of conversion than unexposed employees during 1989-91, but not for 1992. Among the exposed, ward clerks had a risk of conversion (15.6%) only slightly lower than nurses (18.2%). We conclude that employees who worked in areas where patients with active M. tuberculosis infection were cared for, including workers who did not provide direct patient care, had a higher risk of TST conversion than employees who did not work in these areas. Reasons for the decline in risk over time include outbreak termination, fewer admissions of patients with TB, implementation of effective infection control measures, and possible resistance to infection in some members of the study population.

The prevalence of pulmonary and upper respiratory tract symptoms and spirometric test findings among newspaper pressroom workers exposed to solvents.

To investigate the relationship between exposure to organic solvents and the presence of pulmonary and upper respiratory tract mucous membrane symptoms, we conducted a cross-sectional study of 215 newspaper pressroom workers who were occupationally exposed to organic solvent and lubricant mixtures. Thirty-four compositors, who were not occupationally exposed to the solvents or lubricants, served as controls. Pressroom workers and compositors underwent spirometric testing and were also asked about the presence of cough, phlegm, hemoptysis, dyspnea, wheezing, chest tightness, nose or throat irritation, eye irritation, and sinus trouble. The spirometric results did not significantly differ between the two groups. However, the pressroom workers were significantly more likely to report pulmonary or upper respiratory tract mucous membrane symptoms than were compositors (P < 0.005). An exposure-response relationship could be demonstrated when comparing the number of solvents exposed with the total number of symptoms (P < 0.001). Similarly, an exposure-response relationship could be demonstrated when comparing the frequency of use of each of the seven solvents with the total number of symptoms (P < 0.002). Each of these findings was supported in a multivariable linear regression model that adjusted for potential confounders such as age, smoking history, and number of years in the industry. A high prevalence of these symptoms was reported even though the degree of exposure to solvents and lubricants was within the current permissible exposure limits.