[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

[Medicinal tumor treatment of oropharyngeal cancer]. / Medikamentöse Therapie des Oropharynxkarzinoms.

BACKGROUND: The number of patients suffering from human papillomavirus (HPV)-associated oropharyngeal cancer has increased in recent decades. To date, the role of medical therapy in patients with squamous cell carcinoma of the head and neck region has only been established in the refractory or metastatic setting (r/m HNSCC). OBJECTIVE: What are the current treatment options for patients with r/m HNSCC or r/m oropharyngeal cancer? MATERIALS AND METHODS: A literature search was conducted on systemic treatment of oropharyngeal cancer and r/m HNSCC. RESULTS: There is currently no standard treatment for patients with oropharyngeal cancer in refractory or metastatic stages. Since 2017, immunotherapy with checkpoint inhibitors has become increasingly important in the treatment of r/m HNSCC patients. First-line therapy was recently adapted based on the results of the KEYNOTE-48 (KN048) study. For selected patients with r/m HNSCC, there now exists a chemotherapy-free treatment option. Use of immunotherapy also in earlier stages of HNSCC can be expected in the near future. CONCLUSION: Medical therapy of r/m HNSCC patients is in a period of great change. Treatment is increasingly based on combination therapy with checkpoint inhibitors.

[Long-term care facilities during the COVID-19 pandemic : Considerations on the way back to normality]. / Langzeitpflegeeinrichtungen in der COVID-19-Pandemie : Überlegungen auf dem Weg zurück in die Normalität.

Long-term care facilities (LTCF) were and are particularly affected by the COVID-19 pandemic. The dimensions of the outbreaks and the high mortality among residents led to massive restrictions in LTCFs, especially in the area of social contacts and activities but also in areas of medical care. With the start of vaccinations and the improved testing options, the situation has now changed and existing restrictions must be evaluated to determine whether they are still appropriate. In an interprofessional and interdisciplinary group of experts, considerations have been formulated on how a way back to normality could look like in LTCFs.

[Clarification of dizziness in old age : Interdisciplinary diagnostic process]. / Schwindelabklärung im Alter : Interdisziplinärer diagnostischer Prozess.

The clinical symptom dizziness encompasses a broad range of complaints. The prevalence among older adults is high. Over the course of 1 year 50% of people over 80 years old, 30% of those between 70-80 years old and 20% between 60-70 years old contact a physician as a result of dizziness. The diagnostic process has to be well organized. The medical history and clinical examination are frequently underestimated but in many cases are crucial. Extensive investigations should only be carried out in cases of a firmly suspected diagnosis. A good interdisciplinary cooperation can positively influence the diagnostic process. The awareness of red flags also helps to detect emergency patients with dizziness. This article discusses the differential diagnosis of dizziness in older adults and provides appropriate recommendations for the diagnostic process.

[Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy]. / Subgruppenanalyse aus der nicht-interventionellen Beobachtungsstudie REASON: PFS und OS gemäß Alter, Raucherstatus, Geschlecht und histologischem Subtyp unter Verwendung von Gefitinib bzw. chemotherapeutischer Behandlung bei NSCLC-Patienten.

PURPOSE: Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. METHODS: 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. RESULTS: Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). CONCLUSION: A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis.

OPTN/SRTR 2013 Annual Data Report: heart.

The number of heart transplants performed annually continues to increase gradually, and the number of adult candidates on the waiting list increased by 34.2% from 2003 to 2013. The heart transplant rate among active adult candidates peaked at 149.0 per 100 waitlist years in 2007 and has been declining since then; in 2013, the rate was 87.4 heart transplants per 100 active waitlist years. Increased waiting times do not appear to be correlated with an overall increase in waitlist mortality. Since 2008, the proportion of patients on life support before transplant increased from 53.4% to 65.8% in 2013. Medical urgency categories have become less distinct, with most patients listed in higher urgency categories. Approximately 500 pediatric candidates are added to the waiting list each year; the number of pediatric transplants performed each year increased from 293 in 2003 to 411 in 2013. Patient survival among pediatric recipients continues to improve; 5-year patient survival for transplants performed from 2001 through 2008 was 70% to 80%. Medicare paid for some or all of the care for 42.2% of all heart transplant recipients in 2012.

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: results of an open-label, randomized, controlled phase II study (CERTO).

BACKGROUND: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. RESULTS: There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvß3 and αvß5 expression was neither a predictive nor a prognostic indicator. CONCLUSIONS: The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment. CLINICAL TRIAL REGISTRATION ID NUMBER: NCT00842712.

OPTN/SRTR 2012 Annual Data Report: heart.

The number of heart transplants performed annually continues to increase gradually, and the number of adult candidates on the waiting list increased by 25% from 2004 to 2012. The heart transplant rate among active adult candidates peaked at 149 per 100 wait-list years in 2007 and has been declining since; in 2012, the rate was 93 heart transplants per 100 active wait-list years. Increased waiting times do not appear to be correlated with an overall increase in wait-list mortality. Since 2007, the proportion of patients on life support before transplant increased from 48.6% to 62.7% in 2012. Medical urgency categories have become less distinct, with most patients listed in higher urgency categories. Approximately 500 pediatric candidates are added to the waiting list each year; the number of transplants performed each year increased from 274 in 1998 to 372 in 2012. Graft survival in pediatric recipients continues to improve; 5-year graft survival for transplants performed in 2007 was 78.5%. Medicare paid for some or all of the care for nearly 40% of heart transplant recipients in 2010. Heart transplant appears to be more expensive than ventricular assist devices for managing end-stage heart failure, but is more effective and likely more cost-effective.

Application of the optimized CO-rebreathing method for determination of hemoglobin mass in patients with polycythemia vera.

Determination of red cell volume (RCV) might contribute to establishing the diagnosis of polycythemia vera (PV). A novel simplified method to detect RCV through CO rebreathing is nowadays applied in healthy young individuals but was not tested in a clinical or PV setting. The aim of the present study is to evaluate whether this spirometric approach is applicable in older subjects and contributes to PV diagnosis in a proof-of-concept approach. At first, RCV was determined by the optimized CO-rebreathing method in healthy subjects >50 years of age (n = 81, age 66 ± 9 years). Failure rate and age distribution of subjects who failed with CO rebreathing were analyzed. Then, RCV was measured in male PV patients (n = 7) and compared to healthy male controls (n = 35). RCV values in relation to several anthropometric references (body weight, body surface area (BSA), lean body mass (LBM)) were calculated to determine the sensitivity and specificity of established RCV thresholds when using optimized CO rebreathing. In healthy subjects, test failure rate was 9.9 %, but failure was not associated with age. Sensitivity and specificity (sens/spec) to detect PV was 100 %/83 % using the criteria of the PV study group. Using criteria based on BSA, sens/spec was 14 %/100 %. An arbitrary threshold of 50 ml/kg LBM yielded sens/spec of 100 %/97 %. In conclusion, this proof-of-concept indicates that optimized CO rebreathing is applicable in older subjects and allows determining RCV for the diagnosis of PV. Normalized values for RCV measures obtained from CO rebreathing are needed to grant sufficient sensitivity and/or specificity.

[Gender-specific aspects of coronary heart disease]. / Geschlechtsspezifische Aspekte bei der koronaren Herzkrankheit.

The total number of deaths from cardiovascular diseases (CVD) is greater for women than for men, although the mean age at manifestation of CVD is about 10 years older. However, the annual number of cases treated for CVD in acute hospital settings in men exceeds that of women by 50 %. Remarkable gender differences exist in terms of morphological and physiological conditions (e.g. mean coronary vessel diameter; ability to adapt to protective exercise-induced myocardial hypertrophy), as well as of the frequency and clinical significance of somatic risk factors (e.g. smoking). Female body weight increases after menopause and the body shape assumes a more android fat distribution. Women report higher levels of unspecific and affective symptoms. They suffer more from anxiety and depression than men; however, the secondary impact on CVD onset may be less pronounced. The post-acute CVD course is more complicated in women, mainly because they are older and suffer more from multi-morbidity. Whilst male CVD patients aim for a rapid recovery, physical fitness and an increased life expectancy, female patients seek relief from everyday challenges, the maintenance of their independence and emotional support.

OPTN/SRTR 2011 Annual Data Report: heart.

Since 2005, the number of new active adult candidates on the heart transplant waiting list increased by 19.2%. The transplant rate peaked at 78.6 per 100 wait-list years in 2007, and declined to 67.8 in 2011. Wait-list mortality declined over the past decade, including among patients with a ventricular assist device at listing; in 2010 and 2011, the mortality rate for these patients was comparable to the rate for patients without a device. Median time to transplant was lowest for candidates listed in 2006-2007, and increased by 3.8 months for patients listed in 2010-2011. Graft survival has gradually improved over the past two decades, though acute rejection is common. Hospitalizations are frequent and increase in frequency over the life of the graft. In 2011, the rate of pediatric heart transplants was 124.6 per 100 patient-years on the waiting list; the highest rate was for patients aged less than 1 year. The pre-transplant mortality rate was also highest for patients aged less than 1 year. Short- and long-term graft survival has continued to improve. The effect on wait-list outcomes of a new pediatric heart allocation policy implemented in 2009 to reduce pediatric deaths on the waiting list cannot yet be determined.

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity.

BACKGROUND: Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. PATIENTS AND METHODS: SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. RESULTS: The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. CONCLUSION: With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

Lung and heart allocation in the United States.

Lung and heart allocation in the United States has evolved over the past 20-30 years to better serve transplant candidates and improve organ utilization. The current lung allocation policy, based on the Lung Allocation Score, attempts to take into account risk of death on the waiting list and chance of survival posttransplant. This policy is flexible and can be adjusted to improve the predictive ability of the score. Similarly, in response to the changing clinical phenotype of heart transplant candidates, heart allocation policies have evolved to a multitiered algorithm that attempts to prioritize organs to the most infirm, a designation that fluctuates with trends in therapy. The Organ Procurement and Transplantation Network and its committees have been responsive, as demonstrated by recent modifications to pediatric heart allocation and mechanical circulatory support policies and by ongoing efforts to ensure that heart allocation policies are equitable and current. Here we examine the development of US lung and heart allocation policy, evaluate the application of the current policy on clinical practice and explore future directions for lung and heart allocation.

A record of microplastic in the marine nearshore waters of South Georgia.

The polar plastics research community have recommended the spatial coverage of microplastic investigations in Antarctica and the Southern Ocean be increased. Presented here is a baseline estimate of microplastics in the nearshore waters of South Georgia, the first in situ study of the north-east coast of the island. Our results show that the microplastic concentration in seawater at twelve stations in proximity to King Edward Point Research Station ranged from 1.75 ± 5.17 MP/L (mean ± SD), approximately one order of magnitude higher than similar studies of sea surface waters south of the Polar Front. Levels of microplastics in freshwater (sampled from Gull Lake) and precipitation (collected adjacent to the research station) were 2.67 ± 3.05 MP/L, and 4.67 ± 3.21 MP/L respectively. There was no significant difference in the microplastic concentration between seawater sites, and no significant bilateral relationship between concentration and distance from the research station outlets. We report an average concentration of 1.66 ± 3.00 MP/L in wastewater collected from the research station but overall, the counts of microplastics were too low to attach any statistical significance to the similarity in the microplastic assemblages of seawater and wastewater, or assemblages retrieved from penguin species in the region in other studies. Using a calculation described in contemporary literature we estimate the number of microfibres potentially being released from ships and stations annually in the region but acknowledge that further samples are needed to support the figures generated. More extensive research into microplastic distribution, characteristics, and transport in the region is recommended to fully compute the level of risk which this pollutant represents to the ecosystem health of this remote region.

Species-specific impact of microplastics on coral physiology.

There is evidence that microplastic (MP) pollution can negatively influence coral health; however, mechanisms are unknown and most studies have used MP exposure concentrations that are considerably higher than current environmental conditions. Furthermore, whether MP exposure influences coral susceptibility to other stressors such as ocean warming is unknown. Our objective was to determine the physiology response of corals exposed to MP concentrations that have been observed in-situ at ambient and elevated temperature that replicates ocean warming. Here, two sets of short-term experiments were conducted at ambient and elevated temperature, exposing the corals Acroporasp. and Seriatopora hystrix to microspheres and microfibres. Throughout the experiments, gross photosynthesis and net respiration was quantified using a 4-chamber coral respirometer, and photosynthetic yields of photosystem II were measured using Pulse-Amplitude Modulated (PAM) fluorometry. Results indicate the effect of MP exposure is dependent on MP type, coral species, and temperature. MP fibres (but not spheres) reduced photosynthetic capability of Acropora sp., with a 41% decrease in photochemical efficiency at ambient temperature over 12 days. No additional stress response was observed at elevated temperature; photosynthetic performance significantly increased in Seriatopora hystrix exposed to MP spheres. These findings show that a disruption to coral photosynthetic ability can occur at MP concentrations that have been observed in the marine environment and that MP pollution impact on corals remains an important aspect for further research.

Inventory management.

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products.

[Lung cancer from the perspective of internal medicine and surgery]. / Lungenkrebs aus Sicht der Inneren Medizin und Chirurgie.

In previous years numerous advances in diagnostics, staging and therapy of lung cancer have been achieved. Nevertheless, it remains the most frequent cause of death from cancerous diseases. Early diagnosis and exact staging enable multimodal therapy regimens adjusted to age and comorbidities, which result in complete remission in a few and in prolonged survival and good quality of life in most patients. Curative surgery is possible in stage I non-small cell lung cancer (NSCLC) and results in a 5-year survival rates of up to approximately 75%. Using multimodal therapy approaches long-term survival can even be achieved in 40-50% of patients with advanced T4 tumors. However, in NSCLC with distant metastases median survival time is only 8-12 months. In elderly patients with no surgical options low cytotoxic monotherapy can be employed with a palliative intent. In the limited disease stage of small cell lung cancer (SCLC) long lasting remission after polychemotherapy has been observed in a minority of patients. However, in the extensive disease stage polychemotherapy prolongs the survival time of SCLC patients from 1-2 months to approximately 12 months.

Identification of asparagine-linked oligosaccharides involved in tumor cell adhesion to laminin and type IV collagen.

MDW4, a wheat germ agglutinin-resistant nonmetastatic mutant of the highly metastatic murine tumor cell line called MDAY-D2 has previously been shown to attach to fibronectin and type IV collagen, whereas MDAY-D2 and phenotypic revertants of MDW4 attached poorly to these substrates. The increased adhesiveness of the mutant cells appeared to be closely related to a lesion in cell surface carbohydrate structures. In an effort to identify the carbohydrates involved in cell attachment, glycopeptides isolated from mutant and wild-type cells as well as from purified glycoproteins were tested for their ability to inhibit the attachment of MDW4 cells to plastic surfaces coated with fibronectin, laminin, or type IV collagen. The addition of mannose-terminating glycopeptide to the adhesion assay inhibited MDW4 cell attachment to type IV collagen. In contrast, a sialylated poly N-acetyllactosamine-containing glycopeptide, isolated from wheat germ agglutinin-sensitive MDAY-D2 cells but absent in MDW4 cells, inhibited MDW4 attachment to laminin. None of the glycopeptides used in this study inhibited attachment of MDW4 cells to fibronectin-coated plastic. Peptide N-glycosidase treatment of the cells to remove surface asparagine-linked oligosaccharides inhibited MDW4 adhesion to type IV collagen, but not to laminin, and the same treatment of the wheat germ agglutinin-sensitive cells enhanced attachment to laminin. Tumor cell attachment to, and detachment from, the sublaminal matrix protein laminin and type IV collagen are thought to be important events in the metastatic process. Our results indicate that tumor cell attachment to these proteins may be partially modulated by the expression of specific oligosaccharide structures associated with the cell surface.

[Pulmonary complications of transfusion (TACO-TRALI)]. / Complications pulmonaires de la transfusion (TACO-TRALI).

Pulmonary oedemas occurring during or after a blood transfusion appear as the most frequent serious immediate incidents in the French hemovigilance database. They include transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). TACO are a major cause of transfusion-related death in France. TRALI are more and more recognized and notified. In no case, pooled fresh frozen plasma (100 donations) treated with solvent-detergent were involved in French TRALI cases. A logigrame will allow hemovigilance officers to better classify pulmonary oedemas in e-fit, the French hemovigilance database.