Cisplatin-Based Chemotherapy for Pulmonary Metastasized Germ Cell Tumors of the Testis - Be Aware of Acute Respiratory Distress Syndrome

Background: Cisplatin-based combination chemotherapy is regarded as standard of care for patients with advanced germ cell tumors. In patients with lung metastases and a high tumor load, an association between induction chemotherapy and the development of a `tumor-associated' acute respiratory distress syndrome (ARDS) has been hypothesized. Case Report: We report the clinical course of a 19-year-old patient who rapidly developed fatal ARDS during the first cycle of chemotherapy using the PEI regimen (cisplatin, etoposide and ifosfamide) for a metastasized (lung, liver, lymph nodes) germ cell tumor of the testis. Conclusion: Further clinical research in order to better define risk factors for developing ARDS in this patient population as well as novel strategies for the prevention and treatment of ARDS in those patients are necessary

Lung ultrasound predicts clinical course but not outcome in COVID-19 ICU patients: a retrospective single-center analysis

BACKGROUND Point-of-care lung ultrasound (LU) is an established tool in the first assessment of patients with coronavirus disease (COVID-19). Purpose of this study was to evaluate the value of lung ultrasound in COVID-19 intensive care unit (ICU) patients in predicting clinical course and outcome. METHODS We analyzed lung ultrasound score (LUS) of all COVID-19 patients admitted from March 2020 to December 2020 to the Internal Intensive Care Unit, Ludwig-Maximilians-University (LMU) of Munich. LU was performed according to a standardized protocol at ICU admission and in case of clinical deterioration with the need for intubation. A normal lung scores 0 points, the worst LUS has 24 points. Patients were stratified in a low (0-12 points) and a high (13-24 points) lung ultrasound score group. RESULTS The study included 42 patients, 69% of them male. The most common comorbidities were hypertension (81%) and obesity (57%). The values of pH (7.42 ± 0.09 vs 7.35 ± 0.1; p = 0.047) and paO2 (107 80-130 vs 80 66-93 mmHg; p = 0.034) were significantly reduced in patients of the high LUS group. Furthermore, the duration of ventilation (12.5 8.3-25 vs 36.5 9.8-70 days; p = 0.029) was significantly prolonged in this group. Patchy subpleural thickening (n = 38; 90.5{\%}) and subpleural consolidations (n = 23; 54.8{\%}) were present in most patients. Pleural effusion was rare (n = 4; 9.5{\%}). The median total LUS was 11.9 ± 3.9 points. In case of clinical deterioration with the need for intubation, LUS worsened significantly compared to baseline LU. Twelve patients died during the ICU stay (29{\%}). There was no difference in survival in both LUS groups (75{\%} vs 66.7{\%}, p = 0.559). CONCLUSIONS LU can be a useful monitoring tool to predict clinical course but not outcome of COVID-19 ICU patients and can early recognize possible deteriorations

Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel (D2) for First-Line Treatment of Metastatic Breast Cancer

Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly {[}75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Results: Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia >= grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to non-hematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status. Copyright (C) 2011 S. Karger AG, Base

Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer

Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age = grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy. Copyright (C) 2011 S. Karger AG, Base

Bone Loss after Allogeneic Haematopoietic Stem Cell Transplantation: A Pilot Study on the Use of Zoledronic Acid

Purpose. Bone loss is a common phenomenon following allogeneic haematopoietic stem cell transplantation (allo-HSCT). The study aimed on tolerance and efficacy of zoledronic acid (ZA) in patients after allo-HSCT. Methods. 40 patients' with osteoporosis or osteopenia were recruited on this phase II study. ZA was given at a dose of 4 mg IV every 3 months for 2 years (yrs). BMD was determined by dual-energy X-ray absorptiometry (LS lumbar spine, FH femur hip). Patients were evaluated for deoxypyridinoline (Dpd) and calcium excretion by longitudinal measurements. Results. 36 patients who had received at least 3 doses of ZA were evaluable. 26 patients had at least two BMD measurements since baseline (BMD group). Among these patients, BMD increased from 0.97 ± 0.15 to 1.10 ± 0.18 g/cm² (LS baseline—2 yrs, Δ+11.6 ± 6.0%, P < 0.001) and from 0.82 ± 0.10 to 0.91 ± 0.10 g/cm² (FH baseline—2 yrs, Δ+7.5 ± 7.0%, P < 0.001). Factors associated with an increase in BMD were younger age, female donor sex, and immunosuppression with CSA/MTX. Conclusion. ZA was generally well tolerated; it increases BMD and reduces Dpd excretion significantly in patients with bone loss after allo-HSCT

Cardiac Output Measurements in Septic Patients: Comparing the Accuracy of USCOM to PiCCO

USCOM is an ultrasound-based method which has been accepted for noninvasive hemodynamic monitoring in various clinical conditions (USCOM, Ultrasonic cardiac output monitoring). The present study aimed at comparing the accuracy of the USCOM device with that of the thermodilution technique in patients with septicemia. We conducted a prospective observational study in a medical but noncardiological ICU of a university hospital. Septic adult patients (median age 55 years, median SAPS-II-Score 43 points) on mechanical ventilation and catecholamine support were monitored with USCOM and PiCCO (n = 70). Seventy paired left-sided CO measurements (transaortic access = COUS-A) were obtained. The mean COUS-A were 6.55 l/min (±2.19) versus COPiCCO 6.5 l/min (±2.18). The correlation coefficient was r = 0.89. Comparison by Bland-Altman analysis revealed a bias of −0.36 l/min (±0.99 l/min) leading to a mean percentage error of 29%. USCOM is a feasible and rapid method to evaluate CO in septic patients. USCOM does reliably represent CO values as compared to the reference technique based on thermodilution (PiCCO). It seems to be appropriate in situations where CO measurements are most pertinent to patient management

Follow-up for breast cancer - the patients' view

Background: International and national guidelines (S3 guideline) for the surveillance of post-treatment breast cancer patients recommend a clinical follow-up including routine history and physical examination and regular mammograms. The practice of a clinical follow-up has been often discussed, but has been proven not to be inferior when compared to an intensified follow-up in randomized trials. Patients and Methods: The present manuscript reports the patients' view on the basis of a survey including 2000 patients with a history of breast cancer. Results: A total of 452 patients (22.6%) answered the questionnaire. The median age was 62 years (range 23-85 years). More than 80% of the patients were disease-free at the time of the survey. The need for surveillance was affirmed by the majority of patients (>95%), and one third stated that there was a need for more technical efforts during follow-up. In contrast to the follow-up guidelines, the results of the present survey indicated that most of the regularly scheduled follow-up visits were expanded using extensive laboratory and imaging procedures. Conclusion: This survey shows that the majority of physicians obviously do not accept the present follow-up guidelines. A new surveillance study investigating the efficacy of an intensified surveillance based on the improved possibilities of modern diagnostics and endocrine, immunotherapeutic, chemotherapeutic and interventional treatment options is warranted

The Reality in the Surveillance of Breast Cancer Survivors—Results of a Patient Survey

Background: International guidelines for the surveillance of breast cancer patients recommend a minimized clinical follow-up including routine history and physical examination and regularly scheduled mammograms. However, the abandonment of scheduled follow-up examinations in breast cancer survivors remains a contradiction to established follow-up guidelines for other solid tumours.Patients and Methods: We report the patients’ view on the basis of a survey performed in two separate geographical areas in Germany. The questionnaires were sent out to 2.658 patients with a history of breast cancer.Results: A total of 801 patients (30.1%) responded to the questionnaire. The results of the survey can be summarized in two major categories: First, necessity for surveillance was affi rmed by a majority (>95%), and 47.8% of the organized patients answered that there was a need for more intensive diagnostic effort during follow-up. The main expectation from an intensified follow-up was the increased feeling of security as expressed by >80% of the women. Second, the present survey indicates that most of the regularly scheduled follow-up visits were expanded using extensive laboratory and imaging procedures exceeding the quantity of examinations recommended in the present follow-up guidelines.Conclusion: Despite the fact that only one third of the patients responded to the questionnaire, the survey indicates that a majority of physicians who treated these patients still do not accept the present follow-up guidelines. To some extent this may be explained by the observation that patients and possibly also their doctors trust that intensified follow-up increases diagnostic security and survival. Since considerable changes in the treatment options of breast cancer have been made during the last decades a new trial of investigations in follow-up is warranted

Anthracycline-Induced Cardiotoxicity: Cardiac Monitoring by Continuous Wave-Doppler Ultrasound Cardiac Output Monitoring and Correlation to Echocardiography

Background: Anthracyclines are agents with a well-known cardiotoxicity. The study sought to evaluate the hemodynamic response to an anthracycline using real-time continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and echocardiography in combination with serum biomarkers. Methods: 50 patients (26 male, 24 female, median age 59 years) suffering from various types of cancer received an anthracycline-based regimen. Patients' responses were measured at different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1 day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4) and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro-BNP and hs-Troponin T (T0-T4). Results: During the 3-month observation period, the relative decrease in the EF determined by echocardiography was -2.1% (Delta T0-T4, T0 71 +/- 7.8%, T4 69.5 +/- 7%, p = 0.04), whereas the decrease in SV observed using CW-Doppler was -6.5% (Delta T0-T4, T0 54 +/- 19.2 ml, T4 50.5 +/- 20.6 ml, p = 0.14). The kinetics for serum biomarkers were inversely correlated. Conclusions: Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for monitoring the immediate and chronic hemodynamic changes during an anthracycline-based regimen; the results obtained were comparable to those from echocardiography

Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection

Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design