Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.

OBJECTIVES: COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems. STUDY DESIGN: The study presented was conducted as part of the prospective CoVacSer cohort study. METHODS: This study examined sick leave and intake of pro re nata medication after the first, second, and third COVID-19 vaccination in HCWs. Data were collected by using an electronic questionnaire. RESULTS: Among 1704 HCWs enrolled, 595 (34.9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273, the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. CONCLUSION: In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to postvaccination inability to work, which could negatively impact the already strained healthcare system and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.

Characterization of Black Pigmenturia in a Cat with Apocrine Gland Cystadenocarcinoma.

An 8-year-old neutered female domestic shorthair cat was presented for further management of an apocrine gland cystadenocarcinoma. Extensive nodal metastasis was diagnosed and the cat was humanely destroyed 2 months after presentation. Post-mortem histopathology of the cystadenocarcinoma revealed areas of yellow-brown granular pigmentation on light microscopy, staining positively for reducing substances with Schmorl's stain and demonstrating autofluorescence on confocal microscopy. The cat's urine was black and also exhibited autofluorescence, and further analysis revealed increased free pentosidine. Based on these findings, it was presumed that the apocrine gland cystadenocarcinoma was producing lipofuscin-like pigments and that the characteristics of the urine were at least partially secondary to advanced glycation end-products.

[Un- and dedifferentiated endometrial carcinoma : A rare entity with a wide range of differential diagnosis]. / Das un- und dedifferenzierte Endometriumkarzinom : Eine seltene Entität mit breitem differenzialdiagnostischem Spektrum.

Dedifferentiated endometrial carcinomas (ECs) are composed of undifferentiated EC and a FIGO grade 1 or 2 endometrioid carcinoma. The undifferentiated component represents a malignant epithelial neoplasm with no obvious differentiation and immunohistochemical loss of PAX8, E­cadherin and focal expression of EMA and/or CK18 and the predominant presence of nuclear staining for INI1 (SMARCB1) and BRG1 (SMARCA4). The main differential diagnoses include poorly differentiated endometrioid EC, neuroendocrine carcinoma, lymphoma, plasmocytoma, high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas (UUS), carcinosarcomas, and metastases to the endometrium. The histogenesis is not yet fully understood and molecular data are still limited. Some tumors represent a loss of MHL1 and PMS2 staining due to MLH1-promotor methylation. Rare cases are associated with Lynch syndrome or POLE mutation. The un- or dedifferentiated EC represents a high-grade endometrial carcinoma that requires extended surgery and indicates a poor prognosis. In cases with mismatch repair protein deficiency or POLE mutation, immuno-oncological treatment with checkpoint inhibitors are a therapeutic option.

[The 2019 FIGO classification for cervical carcinoma-what's new?] / FIGO-Klassifikation für das Zervixkarzinom 2019 ­ was ist neu?

Numerous therapeutic and prognostic studies of cervical carcinoma have necessitated a revision of the FIGO classification.For microinvasive carcinomas, the horizontal dimension is no longer considered and diagnosis and staging will solely be made by the depth of cervical stromal invasion. Lymphovascular invasion beyond the deepest point of stromal infiltration by tumor cells does not alter the stage.There will be a new subclassification of macroinvasive carcinoma confined to the uterine cervix, which will be made by largest tumor extension as follows: FIGO IB1/T1b1 - invasive carcinoma >0.5 cm depth of stromal invasion and ≤2 cm in largest dimension, FIGO IBII/T1b2: - invasive carcinoma >2 cm and ≤4 cm, FIGO IBII/T1b3 - invasive carcinoma >4 cm. Pelvic as well as para-aortic lymph nodes will be defined as regional nodes. Pelvic lymph node metastases only will be categorised as FIGO IIIC1/pN1a and para-aortic lymph node involvement with or without concomitant pelvic involvement will be FIGO IIIC2/pN1b. Uterine corpus as well as adnexal involvement are not relevant for staging purpose.

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. RESULTS: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). CONCLUSIONS: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CLINICAL TRIALS NUMBER: CFEM345DDE19.

[Cancer patients in operative intensive care medicine]. / Krebspatienten in der operativen Intensivmedizin.

Cancer is one of the leading causes of death worldwide. New targeted and individualized therapies and drugs provide a survival benefit for an increasing number of patients, but can also cause severe side effects. An increasing number of oncology patients are admitted to intensive care units (ICU) because of cancer-related complications or treatment-associated side effects. Postoperative care, respiratory distress and sepsis are the leading causes for admission. Tumor mass syndromes and tumor lysis may require urgent treatment. Traditional anticancer chemotherapy is associated with infections and immunosuppression. Newer agents are generally well-tolerated and side effects are mild or moderate, but overwhelming inflammation and autoimmunity can also occur. Cellular treatment, such as with chimeric antigen receptor modified T­cells, monoclonal and bispecific antibodies targeting immune effectors and tumor cells are associated with cytokine release syndrome (CRS) with hypotension, skin reactions and fever. It is related to excessively high levels of inflammatory cytokines. Immune checkpoint inhibitors can lead to immune-related adverse events (IRAEs), such as colitis and endocrine disorders. Noninfectious respiratory complications, such as pneumonitis can also occur. Recent studies revealed that short-term and medium-term survival of cancer patients is better than previously expected. In this review article we summarize diagnostic and treatment strategies for common life-threatening complications and emergencies requiring ICU admission. Furthermore, strategies for rational admission policies are presented.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Impact of the Weekday of Surgery on Outcome in Gastric Cancer Patients who Underwent D2-Gastrectomy.

BACKGROUND: The impact of the weekday of surgery in major elective cases of the upper-GI has been discussed controversially. The objective of this study was to assess whether weekday of surgery influences outcome in patients undergoing D2-gastrectomy. MATERIALS AND METHODS: Patients who underwent D2-gastrectomy for gastric adenocarcinoma between 1996 and 2016 were included. Weekday of surgery was recognized, and subgroups were analyzed regarding clinical and histopathological differences. Survival analysis was performed based on weekday of surgery, and early weekdays (Monday-Tuesday) were compared with late weekdays (Wednesday-Friday). RESULTS: In total, 460 patients, 71% male and 29% female, were included into analysis. The median age was 65 years. Distribution to each weekday was equal and ranged from 86 cases (Wednesday) to 96 cases (Tuesday). The pT, pN and M category and the rate of patients who underwent neoadjuvant treatment did not show significant differences (p = 0.641; p = 0.337; p = 0.752; p = 0.342, respectively). The subgroups did not differ regarding the number of dissected lymph nodes and rate of R-1/2 resections (p = 0.590; p = 0.241, respectively). Survival analysis showed a median survival of 43 months (95% CI 31-55 months), and there was no single weekday or a combination of weekdays (Mon/Tue vs Wed/Thu/Fri) with a significant favorable or worse outcome (p = 0.863; p = 0.30, respectively). The outcome did not differ regarding mortality within the first 90 days after surgery (p = 0.948). CONCLUSIONS: The present study does not show any evidence for a significant impact of weekday of surgery on short- and long-term outcome of patients undergoing gastrectomy for gastric adenocarcinoma.

[Enteral nutrition therapy in critical care : Current knowledge, controversies, and practical implementation]. / Enterale Ernährungstherapie in der Intensivmedizin : Aktuelles Wissen, Kontroversen und praktische Umsetzung.

Nutrition therapy is a cornerstone in critical care. Early enteral feeding in patients who are unable to meet caloric requirements from oral intake is associated with better clinical outcomes. However, there are still uncertainties about optimal timing, dose, and formula selection of enteral nutrition in critically ill patients. In the present article, an overview of current knowledge and practical strategies for successful implementation of enteral nutrition in intensive care patients is given.

Antibiotic consumption after implementation of a procalcitonin-guided antimicrobial stewardship programme in surgical patients admitted to an intensive care unit: a retrospective before-and-after analysis.

PURPOSE: To analyse antibiotic use density (AD)--World Health Organization defined daily doses/1,000 patient-days--before and after implementation of a local antimicrobial stewardship programme (ASP) in conjunction with a procalcitonin (PCT)-guided protocol in a surgical intensive care unit (ICU). METHODS: In this retrospective observational study, data on 2,422 ICU patients between 2010 and 2012 were analysed. In 2011, an ASP in conjunction with a PCT protocol had been introduced into clinical practice. In a multivariate analysis, hospital mortality, length of stay (LOS) in hospital and ICU LOS were adjusted for effects from effective cost weight, gender, and age. AD and changes in the use of antibiotic classes were analysed. RESULTS: AD decreased from 1,005.0 in 2010 to 791.9 in 2012 which is a total reduction of 21.2%. Consumption of aminoglycosides, cephalosporins and quinolones showed a marked reduction, whereas the use of penicillins did not change significantly. The multivariate models revealed no relevant changes in mortality rate, ICU LOS and hospital LOS. CONCLUSIONS: Implementation of an ASP in conjunction with a PCT protocol in 2011 was associated with a marked decrease in total AD and led to a significant change in the spectrum of antibiotics. Clinical outcomes appeared to remain unchanged over the study period.

[New FIGO classification of ovarian, fallopian tube and primary peritoneal cancer]. / Neue FIGO-Klassifikation des Ovarial-, Tuben und primären Peritonealkarzinoms.

During recent years paramount changes have occurred in the pathogenesis of ovarian cancer and recent clinical studies identified new prognostic factors. Consequently, the FIGO has established a new staging system collectively covering carcinomas derived from the ovaries, the fallopian tubes and primary peritoneal cancers as well as malignant ovarian germ cell and sex-cord stromal tumors. The new staging system started on 01 January 2014. Major changes occurred in the FIGO IC/T1c stage with surgical spill (FIGO IC1/T1c1) versus capsule ruptured before surgery or tumor on ovarian or fallopian tube surface (FIGO IC2/T1c2) versus malignant cells in the ascites or peritoneal washings (FIGO IC3/T1c3). The regional lymph node metastases were subcategorised using a cut-off value of 10 mm as the largest dimension of the metastatic deposits. Distant metastases (excluding peritoneal metastases) were substaged as FIGO IVA/M1a in cases of cytologically or histologically proven pleural involvement and as FIGO IVB/M1b in cases of parenchymal metastases and metastases in extra-abdominal organs (including lymph nodes outside the peritoneal cavity and the inguinal lymph nodes).

[Morphology of secondary ovarian tumors and metastases]. / Morphologie sekundärer Ovarialtumoren/Ovarmetastasen.

The distinction between primary and secondary (metastatic) ovarian tumors is essential for the selection of appropriate surgical interventions, chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic tumors of the ovary range between 5 % and 30 %. The majority of ovarian metastases in Europe and North America derive from colorectal (25-50 %) and breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous tumors. Major features favoring metastasis include bilaterality, size < 10 cm, ovarian surface involvement, extensive intra-abdominal spread, and infiltrative growth within the ovary involving the corpus albicans and corpora lutea. An algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct categorization in approximately 85 % of the cases. Although immunohistochemistry (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a valuable role and is paramount in the diagnosis, the results must be interpreted with caution and within the relevant clinical and histopathological context. It is necessary to note that the correct diagnosis of ovarian metastases always needs interdisciplinary and multidisciplinary approaches.

Reproducibility of histopathologic tumor grading in penile cancer--results of a European project.

Since reliable molecular prognostic parameters for inguinal lymph metastases in penile cancer are not available, tumor grading is often used as a surrogate prognostic tool for the indication of inguinal lymphadenctomy and has been integrated into the current TNM classification for penile cancer. The reliability of tumor grading is under discussion. We examined interobserver grading variability in 90 primary penile carcinomas, assessed by 12 different uropathologists from five European countries. Tumor grading, following the CAP scheme, was compared, and interobserver variability was calculated using kappa statistics. The interobserver variability was high as reflected by an overall low kappa coefficient (mean k = 0.34) and reached a moderate level only in 26.4 % of the cases (range 0.02-0.67). The percentage of G1 tumors assigned ranged from 8.6 to 52.5 %, G2 tumors from 27.1 to 72.6 % and G3 tumors from 11.7 to 48.7 %. Only some observers assigned G4 with a range of 0.6-21.9 %. Subdivision into low and high grade according to UICC and EAU classifications differed significantly (P < 0.001). Low reproducibility of grading in penile carcinomas with the favored method does not allow a reliable prognostication of tumor aggressiveness. Inclusion of histological grading into the TNM classification currently seems not to be a benefit.

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1-5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5-10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

Non-invasive continuous arterial pressure monitoring with Nexfin does not sufficiently replace invasive measurements in critically ill patients.

BACKGROUND: In this study, we tested the reliability of a non-invasive finger-cuff-based continuous arterial blood pressure monitoring device (Nexfin, BMEYE, Amsterdam, NL) in critically ill surgical patients. METHODS: Invasive intra-arterial and non-invasive arterial pressure measurements from 25 patients during a 4-h period were compared at five time points. Correlation and linear regression analysis were used and mean bias, precision [sd of bias] and limits of agreement (LOA) [bias (2.0 sd)] were calculated using the Bland-Altman method. RESULTS: Eight data pairs were excluded because of error message from the non-invasive technique, and thus a total of 117 data pairs were analysed. Overall, correlation between mean arterial pressure (MAP) was r(2)=0.50. Bias, precision, and LOA between invasive and non-invasive MAP were 6 (12) and -18 to +30 mm Hg. In patients requiring norepinephrine (83 data pairs), correlation was r(2)=0.28 and bias, precision, and LOA were 6 (13) and -20 to +32 mm Hg, whereas in patients not receiving norepinephrine (34 data pairs) r(2) was 0.80 and mean bias, precision, and LOA were 6 (11) and -16 to +28 mm Hg. In patients with peripheral oedema (49 data pairs), r(2) was 0.40 and mean bias, precision and LOA were 7 (15) and -23 to +37 mm Hg. In patients without oedema (64 data pairs), r(2) was 0.66 and mean bias, precision, and LOA were 5 (9) and -13 to +23 mm Hg. CONCLUSIONS: Non-invasive blood pressure monitoring with Nexfin does not seem to be sufficiently accurate to replace intra-arterial invasive blood pressure measurements in critically ill patients.

Comment on "Intensifying weathering and land use in Iron Age Central Africa".

Bayon et al. (Reports, 9 March 2012, p. 1219) interpreted unusually high aluminum-potassium ratio values in an Atlantic sediment core as indicating anthropogenic deforestation around 2500 years before the present (B.P.). We argue that there is no terrestrial evidence for forest destruction by humans and that the third millennium B.P. rainforest crisis can be clearly attributed mostly to climatic change.

Oxidative protein damage and the proteasome.

Protein damage, caused by radicals, is involved in many diseases and in the aging process. Therefore, it is crucial to understand how protein damage can be limited, repaired or removed. To degrade damaged proteins, several intracellular proteolytic systems exist. One of the most important contributors in intracellular protein degradation of oxidized, aggregated and misfolded proteins is the proteasomal system. The proteasome is not a simple, unregulated structure. It is a more complex proteolytic composition that undergoes diverse regulation in situations of oxidative stress, aging and pathology. In addition to that, numerous studies revealed that the proteasome activity is altered during life time, contributing to the aging process. In addition, in the nervous system, the proteasome plays an important role in maintaining neuronal protein homeostasis. However, alterations in the activity may have an impact on the onset of neurodegenerative diseases. In this review, we discuss what is presently known about protein damage, the role of the proteasome in the degradation of damaged proteins and how the proteasome is regulated. Special emphasis was laid on the role of the proteasome in neurodegenerative diseases.

[HPV-associated alterations of the vulva and vagina. Morphology and molecular pathology]. / HPV-assoziierte Veränderungen an Vulva und Vagina. Morphologie und Molekularpathologie.

Non-neoplastic HPV-induced alterations of the vulva and vagina are frequent. The traditional three-tier grading system of vulvar intraepithelial neoplasia (VIN) will be replaced by the definition of usual and simplex type of VIN. The usual type is characterized by a strong association to high-risk HPV infections, the occurrence at younger age and multifocality, mostly associated with non-keratinizing squamous cell carcinoma. The differentiated (or simplex) type is rare and shows an association to older age and p53 alterations and is typically diagnosed co-incidentally with keratinizing squamous cell carcinoma. Vaginal intraepithelial neoplasia (VAIN) is still graded into VAIN 1-3 where VAIN 1 and 2 are mostly associated with low-risk HPV infections and a high spontaneous regression rate whereas VAIN 3 represents a high-risk HPV-associated lesion with capable progression into (micro-)invasive carcinoma. The differential diagnosis between a non-neoplastic condylomatous lesion and VIN common type and VAIN may be aided by p16 immunohistochemistry. The HPV-associated invasive vulvo-vaginal cancers are verrucous carcinoma (low-risk HPV) and the high-risk HPV-induced (non-keratinizing) squamous cell carcinoma (NOS), the condylomatous (warty) carcinoma and the very rare vaginal squamo-transitional carcinoma.

[Fulminant pulmonary artery embolism in the early postoperative phase. Use of transesophageal echocardiography in acute diagnostics]. / Fulminante Lungenarterienembolie in der frühen postoperativen Phase. Einsatz der transösophagealen Echokardiographie in der Akutdiagnostik.

Acute pulmonary embolism is a serious perioperative complication with a high mortality. A case of early onset pulmonary embolism with acute right heart failure and resuscitation after spinal surgery is reported. The diagnosis was rapidly and reliably confirmed by transesophageal echocardiography (TEE) and a right atrial thrombus was detected. Persistent life-threatening hemodynamic instability required thrombolysis with 100 mg recombinant tissue-type plasminogen activator (rt-PA). The patient survived this critical situation but sustained permanent paraparesis.

Restricted dispersal in a continuously distributed marine species: common bottlenose dolphins Tursiops truncatus in coastal waters of the western North Atlantic.

The marine environment provides an opportunity to examine population structure in species with high dispersal capabilities and often no obvious barriers to genetic exchange. In coastal waters of the western North Atlantic, common bottlenose dolphins, Tursiops truncatus, are a highly mobile species with a continuous distribution from New York to Florida. We examine if the highly mobile nature coupled with no obvious geographic barriers to movement in this region result in a large panmictic population. Mitochondrial control region sequences and 18 microsatellite loci indicate dolphins are partitioning the habitat both latitudinally and longitudinally. A minimum of five genetically differentiated populations were identified among 404 samples collected in the range of New Jersey to northern Florida using both genetic marker types, some inhabiting nearshore coastal waters and others utilizing inshore estuarine waters. The genetic results reject the hypothesis of a single stock of coastal bottlenose dolphins put forth after the 1987-1988 epizootic that caused a large-scale die-off of dolphins and suggest instead the disease vector was transferred from one population to the next as a result of seasonal migratory movements of some populations. These coastal Atlantic populations also differ significantly from bottlenose dolphin samples collected in coastal waters of the northern Gulf of Mexico, implying a long-term barrier to movement between the two basins.