Adequate Prophylaxis Research Articles

Abstract PS13-35: Evaluation of age as a risk factor for CINV in breast cancer patients: Post-hoc analysis of the German real-world AkyPRO study

Abstract Background: The primary objective of the prospective, non-interventional study (NIS) AkyPRO was the evaluation of quality of life (QoL) in adult cancer patients (pts) receiving NEPA as antiemetic prophylaxis. Secondary endpoints were efficacy and safety of NEPA. NEPA is administered as an oral fixed dose combination of 300 mg of the neurokinin-1-receptor antagonist - (NK1RA) netupitant and 0,5 mg of the 5-hydroxytryptamin-3-receptor antagonist (5-HT3RA) palonosetron once per chemotherapy cycle as primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV) associated with moderately (MEC) or highly (HEC) emetogenic chemotherapy. In modern antiemetic guidelines, anthracycline/ cyclophosphamide (AC) - containing chemotherapy (AC-CT) is classified as HEC requiring triple antiemetic prophylaxis with a 5-HT3RA, a NK1RA and dexamethasone. Pts with breast cancer (BC) have additional risk factors for nausea and vomiting, like female sex and younger age, thus representing a high-risk group for CINV. Here, we present a post-hoc analysis of quality of life data and effectiveness of NEPA in the subgroup of BC pts in two age groups ≥ and < 60 years (y), who were treated with AC-CT in the AkyPRO NIS. Methods: The AkyPRO NIS has been conducted to evaluate quality of life and effectiveness of antiemetic prophylaxis with NEPA in cancer pts with various cancer entities receiving single day or two day MEC or HEC in a real life situation. Quality of life (QoL) was recorded by FLIE questionnaires. Effectiveness of NEPA as indicated by complete response (CR: no vomiting, no rescue medication), additional medication, and adverse events were recorded in patient diaries over three consecutive chemotherapy cycles. Patients and physicians documented overall antiemetic control on a 4-point scale (very good, good, satisfactory, poor). Results: In total, the AkyPro NIS enrolled 2,427 pts. 1,428 pts (65.7 %) had breast cancer. In this post hoc analysis 1,197 BC pts receiving AC-CT (83 % of all BC pts) were evaluated. 782 pts (65%) were <60y, 415 (35%) ≥ 60y old. Most pts received AC-CT in the adjuvant or neoadjuvant setting. Pts ≥ 60y reported a higher CR rate in the overall phase over 3 cycles (c1 88%, c2 90%, c3 88%) than pts <60y (c1 78%, c2, 78%, c77%). Pts ≥ 60y also experienced moderate or severe nausea less frequently, with the non-significant nausea (NSN) rate being 67, 67, 70% c1-c3 in these pts vs. 57, 59, 58% in c1-c3 in younger pts. QoL data confirmed this observation. Older pts reported more often to have no impact on daily life (NIDL) due to nausea (58-62% in c1-c3) than younger pts (50-54% in c1-c3). Comparison of patients’ and physicians’ perception of antiemetic treatment effectiveness revealed that in both groups the majority estimated the effectiveness of antiemetic prophylaxis with NEPA high and comparably well and good or very good. Conclusion: This real-life study confirmed the effectiveness of NEPA in preventing CINV in the subgroup of BC pts receiving AC-chemotherapy. Pts ≥ 60y experienced less CINV compared to pts <60y, confirming that younger age represents a risk factor for CINV and indicating that the choice of an adequate antiemetic prophylaxis is crucial in this group of pts. Citation Format: Joerg Schilling, Steffi Busch, Martin Hollaender, Gabriele Kaltenecker, Eberhard Müller, Thomas Resch, Angelika Till, Meinholf Karthaus. Evaluation of age as a risk factor for CINV in breast cancer patients: Post-hoc analysis of the German real-world AkyPRO study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-35.

Pneumococcal Serotype-specific Opsonophagocytic Activity in Interleukin-1 Receptor-associated Kinase 4-deficient Patients.

The antibody response after pneumococcal vaccines and their effectiveness against invasive pneumococcal disease (IPD) in patients with interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency have not been fully evaluated. Here, we evaluated pneumococcal serotype-specific opsonophagocytic activity (OPA) in IRAK4-deficient patients along with their clinical course. We investigated 6 IRAK4-deficient patients in Japan, whose attending physicians could be contacted. We performed OPA measurements using stored and more recent serum samples obtained from these patients. All patients had received pneumococcal vaccination. Among the 3 patients who had IPD, 2 had an episode of pneumococcal meningitis and the other developed pneumococcal bacteremia 3 years after the occurrence of pneumococcal meningitis. Only one episode of invasive bacterial infection was caused by a Streptococcus pneumoniae vaccine-type strain. An increased opsonization index was found in the sera after vaccination for all IRAK-deficient patients, including when the 23-valent pneumococcal polysaccharide vaccine was used. A significant increase in levels of OPA against most of the pneumococcal vaccine antigens was observed for all IRAK4-deficient patients. However, IPD could not be prevented by pneumococcal vaccination alone. Therefore, adequate prophylaxis should be provided with antibiotics at least until 8 years of age, along with regular immunoglobulin therapy, particularly during the infantile period.

High incidence of postoperative infections after pancreaticoduodenectomy: A need for perioperative anti-infectious strategies

ObjectivesPostoperative infections occur frequently after pancreaticoduodenectomy, especially in patients with bile colonization. Recommendations for perioperative anti-infectious treatment are lacking, and clinical practice is heterogenous. We have analyzed the effects of bile colonization and antibiotic prophylaxis on postoperative infection rates, types and therapeutic consequences. MethodsRetrospective observational study in patients undergoing pancreaticoduodenectomy with intraoperative bile culture. Data on postoperative infections and non-infectious complications, bile cultures and antibiotic prophylaxis adequacy to biliary bacteria were collected. ResultsAmong 129 patients, 53% had a positive bile culture and 23% had received appropriate antibiotic prophylaxis. Postoperative documented infection rate was over 40% in patients with or without bile colonization, but antibiotic therapy was more frequent in positive bile culture patients (77% vs. 57%, P=0,008). The median duration of antibiotic therapy was 11 days and included a broad-spectrum molecule in 42% of cases. Two-thirds of documented postoperative infections involved one or more bacteria isolated in bile cultures, which was associated with a higher complication rate. While bile culture yielded Gram-negative bacilli (57%) and Gram-positive cocci (43%), fungal microorganisms were scarce. Adequate preoperative antibiotic prophylaxis according to bile culture was not associated with reduced infectious or non-infectious complication rates. ConclusionPatients undergoing pancreaticoduodenectomy experience a high rate of postoperative infections, often involving bacteria from perioperative bile culture when positive, with no preventive effect of an adequate preoperative antibiotic prophylaxis. Increased postoperative complications in patients with bile colonization may render necessary a perioperative antibiotic treatment targeting bile microorganisms. Further prospective studies are needed to improve the anti-infectious strategy in these patients.

Coronavirus syndrome: COVID-19 psychotrauma.

The authors propose term “coronavirus syndrome” for the mental disorder that is a psychical response to the global problem of COVID-19 pandemic. This syndrome will affect up to 10% of the population and we could already observe acute stress reactions to the spread of the infection and changes in people’s ordinary lifestyle. However, the most severe response will be seen later, in this case the catastrophe is similar to the clinical picture of post-traumatic stress disorder. The problem is that coronavirus syndrome will affect the working capacity of population at the period, when economical recovery is essential. The risk groups are health caregivers who worked in COVID departments; patients recovered from a severe form of the disease; people who have lost their loved ones; and those who have suffered significant financial losses or lost their jobs. Adequate prophylaxis of coronavirus syndrome especially in high-risk groups are important for maintaining global mental health and economy.

Prevalence of Deep Vein Thrombosis in Patients Supported With Extracorporeal Membrane Oxygenation.

Prevalence of Deep Vein Thrombosis in Patients Supported With Extracorporeal Membrane Oxygenation.

Comparison of two escalated enoxaparin dosing regimens for venous thromboembolism prophylaxis in obese hospitalized patients.

Standard fixed-dose enoxaparin dosing regimens may not provide adequate prophylaxis against venous thromboembolism among obese hospitalized patients. While several escalated doses have been shown to result in more frequent attainment of target anti-factor Xa levels than standard doses, few studies compare escalated doses to each other. In this prospective, multi-center trial, enoxaparin 0.5mg/kg daily (weight-based dosing) and enoxaparin 40mg twice daily were compared to determine if either dose resulted in more frequent attainment of anti-factor Xa levels within the goal range of 0.2-0.5IU/mL. Eighty patients with a BMI ≥ 40kg/m2 were enrolled. There was no difference in the percent of patients achieving goal anti-factor Xa levels (72.5% vs. 70.0%, respectively; p = 0.72). Patients were more likely to attain anti-factor Xa levels below goal range than above. No bleeding or thrombotic events occurred. Either weight-based or twice-daily escalated enoxaparin dosing regimens appear effective at achieving target anti-factor Xa levels among hospitalized patients, and no safety events were noted. Future studies are needed to determine the clinical significance of this result.

Epidemiological Study of Outpatients in Rabies Post-Exposure Prophylaxis Clinics - Tianjin Municipality, China, 2020.

What is already known on this topic?Rabies remains a serious public health problem in China. The only way to prevent the fatal disease was through timely and adequate post-exposure prophylaxis (PEP).What is added by this report?Among all the 126,133 cases visited Tianjin PEP clinics during 2020, more than 90% of the patients were injured by domestic dogs or cats, and about 70% of the animals received vaccination. Most outpatients have knowledge of rabies and show high compatibility with PEP.What are the implications for public health practice?To better control rabies, we need to pay more attention to people who lack knowledge of rabies and help them gain awareness of PEP.

Uticaj antigljivične profilakse na pojavu gljivičnih infekcija kod bolesnika u programu alogene transplantacije

Introduction: Patients with hematologic malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia (AML/ALL), myelodysplastic syndrome (MDS), and those undergoing allergenic stem cell transplantation (alloSCT) are at the highest risk of invasive fungal infections (IFI). The most common causative agents are Candida spp. and Aspergillus spp. Among the strategies for preventing IFIs is the adequate implementation of antifungal prophylaxis recommended by the NCCN (National Comprehensive Cancer Network). Aim: The aim of the study was to analyze the occurrence of IFIs in these patients, as well as to analyze the impact and importance of timely antifungal prophylaxis with regards to the development of these infections. Materials and methods: The retrospective study included 42 patients, of the average age of 35 years, who underwent the allo-SCT program, between 2017 to 2019, and received antifungal prophylaxis at the Clinic for Hematology of the Clinical Center of Serbia (CCS). Based on information obtained from medical histories, databases were formed. Statistical analysis included descriptive statistical methods that were performed in the SPSS program. Results: Nineteen (45.2%) patients presented with the clinical manifestation of oral candidiasis. Invasive pulmonary aspergillosis developed in only 3 (7.1%) patients. There was a statistically significant association between clinically manifest aspergillosis (7.1%) and the presence of antigens (Galactomannan) in these patients (p <0.001). There was also a statistically significant association between clinically manifest aspergillosis and graft weakness: 2 (66.6%) vs. 1 (33.3%), (p = 0.016). Conclusion: The use of adequate antifungal prophylaxis significantly reduces the incidence of IFIs in patients undergoing the allo-SCT program, and this contributes to the reduction of morbidity and mortality.

Are We Using the Adequate Antibiotic Prophylaxis in Biliary Surgeries?

Introduction: Patients undergoing hepato-pancreato-biliary surgery frequently have preoperative cholestasis and ERCP or preoperative biliary drainage may be necessary. This is a known higher risk for bacterobilia and leads to a higher risk for developing surgical site infections. Standard antibiotic prophylaxis may not be totally effective in this population.

The Incidence of Venous Thromboembolism in Asymptomatic Carriers of a Deficiency of Antithrombin, Protein C, or Protein S: A Prospective Cohort Study

AbstractDeficiencies of antithrombin, protein C, and protein S are associated with an increased risk of venous thromboembolism. The objective of this study was to prospectively assess the incidence of venous thromboembolism in nontreated asymptomatic subjects with such a deficiency. We conducted a prospective cohort study in asymptomatic family members of unselected patients who presented with a venous thromboembolic event and who were found to have a deficiency of antithrombin, protein C, or protein S. No anticoagulant prophylaxis was given to the study participants, except during risk periods for venous thromboembolism. All venous thromboembolic events were diagnosed by objective diagnostic tests. A total of 208 individuals with a mean age of 37 years (range, 15 to 79) were included in the study. A total of 611 patient observation years was obtained. Nine venous thromboembolic events occurred, resulting in an annual incidence of 1.5% (95% confidence interval [CI], 0.7 to 2.8) for the 3 deficiencies combined. Five of these events occurred spontaneously, resulting in an annual incidence of spontaneous venous thromboembolism of 0.8% (95% CI, 0.3 to 1.9). For antithrombin, protein C, and protein S deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%, respectively. Thirty-four subjects experienced a total of 40 risk periods during which 4 venous thromboembolic events occurred (10% per risk period). We conclude that the use of continuous anticoagulant prophylaxis seems not warranted in asymptomatic individuals with a deficiency of antithrombin, protein C, or protein S. During risk periods for venous thromboembolism, adequate anticoagulant prophylaxis is necessary.

Vitamin K deficiency-induced spontaneous haemopericardium and cardiac tamponade in an infant with alpha-1 antitrypsin deficiency: a case report.

Background Vitamin K deficiency bleeding is a life-threatening complication in early infancy. Exclusive breastfeeding and neonatal cholestasis syndromes, most notable α-1-antitrypsin deficiency, have been reported to be risk factors. Intracranial haemorrhage is most common. No association to haemopericardium has been reported before.Case summary We report on an 11 weeks old at term-born infant, who presented with severe anaemia and signs of cardiogenic shock. Immediately echocardiography was done and depicted cardiac tamponade. Pericardiocentesis was performed and a significant amount of haemorrhagic fluid was removed. Further workup revealed deranged coagulation parameters, cholestatic liver disease, and reduced α-1-antitrypsin levels. Despite normal brain sonography, a small cerebral haemorrhage was detected on magnetic resonance imaging. A genetic test finally proofed homozygotic mutation of the SERPINA1-gene and confirmed the diagnosis of α-1-antitrypsin deficiency as the underlaying cause. After initial replacement of coagulation factors, erythrocytes and vitamin K, the infant recovered. Eighteen weeks after discharge, the infant is still on vitamin K supplementation. She did not have any further bleedings and no neurologic or developmental impairment.Discussion Alpha-1-antitrypsin deficiency can lead to vitamin K deficiency in young infants even with adequate prophylaxis. Spontaneous haemorrhagic pericardial effusion was a new manifestation of vitamin K deficiency bleeding in our patient and should be considered and ruled out in young infants who present with acute anaemia and poor clinical condition.

COVID-19 prevalence among health-care workers of Gastroenterology department: An audit from a tertiary-care hospital in India.

Background and AimIn the present coronavirus disease‐19 (COVID‐19) era, health‐care workers (HCWs) warrant special attention because of their higher risk and potential to transmit the disease. Gastroenterology services include emergency and critical care along with the endoscopy procedures, which have aerosol‐generating potential. This study was aimed at auditing the COVID‐19 impact on HCWs working in the Gastroenterology department of our hospital.MethodsThe COVID‐19 status of 117 HCWs was collected using either polymerase chain reaction (PCR) or Immunoglobulin G (IgG) seroassay. COVID‐19 positivity was correlated with demographic characteristics, job profile, area of work, and medical history.ResultsThirty‐eight HCWs (32.48%) showed evidence of COVID‐19 using PCR (23.93%) or only IgG assay (8.55%). Endoscopy technicians (68.75%) exhibited significantly higher (P = 0.003) COVID‐19 incidence compared to doctors (20.69%). Those working in the critical care units exhibited a trend toward higher COVID‐19 incidence (42.86%). None of the six HCWs who received adequate hydroxychloroquine prophylaxis developed evidence of COVID‐19. All the HCWs with COVID‐19 disease recovered. However, there was a considerable loss of “man‐days.”ConclusionsIn our setting, we observed a high COVID‐19 risk for HCWs working in the Gastroenterology department, with the highest risk among the endoscopy technicians. A more stringent triaging and pretesting of patients, as well as HCWs, might decrease the risk of COVID‐19. Further multicenter studies are needed to evaluate the risk and related parameters.

Increased Inhibitory KIR-Ligand Interactions Confer Relapse Protection Following HLA Matched Unrelated Donor HCT for AML

Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated graft versus leukemia effect (GVL) after hematopoietic stem cell transplant (HCT) for AML. There is considerable heterogeneity in the KIR gene and KIRL content of individuals, making it difficult to estimate the full clinical impact of NK cell alloreactivity following HCT. Herein, we validate a mathematical model accounting for KIR-KIRL interactions identifying donors with optimal NK cell-mediated alloreactivity and GVL. This retrospective study was performed on de-identified donor and recipient demographic and clinical outcomes data provided by the Center for International Blood and Marrow Transplant Research (CIBMTR). Donor recipient pairs (DRP) who underwent unrelated donor (URD) HCT for early and intermediate AML were included. KIR-KIRL interaction values were assigned as follows; if an inhibitory KIR (iKIR) on the NK cell encounters a ligand on its target, this will give the NK cell an inhibitory signal and this is scored as a single interaction(Figure 1b), as is the case, if there is no ligand for an inhibitory KIR, i.e., missing KIRL (mKIRL) (Figure 1c). Finally, activating KIR (aKIR) interacting with its ligands is similarly scored(Figure 1a). The absolute values of the iKIR and mKIR scores were summed to calculate the composite inhibitory-missing ligand (IM)-KIR score (Figure 1d). The study cohort was comprised of 2365 donor-recipient pairs (DRP) who underwent URD HCT for early or intermediate AML. Mean age was 53 years; 85% of DRPs were high-resolution 8/8 HLA-matched for HLA-A, -B, -C, and -DRB1. All patients received T cell replete grafts; 42% (n=996) received in vivo T cell depletion, 937 (94%) with anti-thymocyte globulin (ATG); 86% received a graft of mobilized peripheral blood stem cells (PBSC), 59% received myeloablative conditioning. This cohort was primarily of Caucasian descent (89%). When adjusted for recipient age, donor age, CMV status, KPS, GVHD prophylaxis, cytogenetics, disease status, conditioning regimen, in vivo T cell depletion, graft source, and sex match, relapse risk was significantly reduced in donor-recipient pairs (DRP) with higher inhibitory KIR-KIRL interaction and missing KIRL (mKIR) scores, with HR=0.86 (P=0.01) & HR=0.84 (P=0.02) respectively. This effect was not observed with activating KIR-KIRL interactions. Chronic GVHD and TRM were not significantly affected by iKIR, mKIR or aKIR. Given the significant individual impact of iKIR and mKIR, the summed inhibitory-missing ligand (IM-KIR) score was next assessed, and when this score was 5 (as opposed to <5), the IM-KIR score was also associated with lower relapse risk, HR 0.8 (P=0.004) (Figure 2a). Acute and chronic graft vs. host disease (GVHD), survival, GRFS, and relapse-free survival were not significantly different, likely due to increased TRM among these patients, HR 1.32 (P=0.01). Interaction analysis indicated that amongst the HLA matched DRP, ATG recipients with IM-KIR=5, had a lower relapse rate compared to those with an IM-KIR<5, HR 0.61 (p=0.001) (Figure 2b), among the cohort who did not receive ATG there was no significant difference in relapse among IM-KIR=5 and IM-KIR<5; thus, the use of ATG significantly modified the effect of IM KIR score in an interaction analysis (p=0.049), suggesting higher NK cell magnitude of KIR-KIRL interaction may compensate for the general increase of relapse in those who receive in vivo T cell depletion. Nevertheless, TRM was also increased in these patients, HR 1.49 (p=0.034), likely abrogating survival advantage from a lower relapse risk. This large international study confirms that unrelated DRPs with greater magnitude of inhibitory KIR-KIRL interactions confer significant relapse protection after MUD HCT in standard-risk AML. This challenges the notion that KIR are irrelevant to donor selection. Future clinical trials evaluating donor selection for URD HCT should include this measure to evaluate its value prospectively in uniformly treated patient cohorts, with adequate GVHD and antiviral prophylaxis to mitigate TRM. Disclosures No relevant conflicts of interest to declare.

Infections in Patients with Chronic Granulomatous Disease Treated with Tumor Necrosis Factor Alpha Blockers for Inflammatory Complications.

Management of inflammatory complications of chronic granulomatous disease (CGD) is challenging. The aim of this study was to assess safety, with a focus on infections, and effectiveness of tumor necrosis factor alpha (TNF-α) blockers in CGD patients. A retrospective, single-center cohort study of CGD patients treated by anti-TNF-α agents at Necker-Enfants Malades University Hospital (Paris, France) and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH). Between 2006 and 2019, 14 (X-linked: n = 10, 71.4%; autosomal-recessive: n = 4, 28.6%) CGD patients with gastrointestinal (n = 12, 85.7%), pulmonary (n = 10, 71.4%), cutaneous (n = 3, 21.4%), and/or genitourinary (n = 2, 14.3%) inflammatory manifestations received one or more doses of infliximab because of steroid-dependent (n = 7, 50%), refractory (n = 4, 28.6%) inflammatory disease or as first-line drug (n = 2, 14.3%; missing data, n = 1). All patients received adequate antimicrobial prophylaxis. Infliximab achieved complete (n = 2, 14.3%) or partial (n = 9, 64.3%) response in 11 (78.6%) patients. Seven (50%) patients were switched to adalimumab. During anti-TNF-α treatment, 11 infections (pneumonia, adenitis, invasive candidiasis, each n = 2; intra-abdominal abscess, bacteremic salmonellosis, Pseudomonas aeruginosa-related folliculitis, cat-scratch disease, proven pulmonary mucormycosis, each n = 1) occurred in 7 (50%) patients. All infectious complications had a favorable outcome. Anti-TNF-α treatment was definitively stopped because of infection in two patients. Nine (64.3%) patients finally underwent hematopoietic stem cell transplantation. No death occurred during follow-up. Anti-TNF-α treatment could improve the outcome of severe inflammatory complications in CGD patients, but increases their risk of infections. We suggest that anti-TNF-α treatment might be of short-term benefit in selected CGD patients with severe inflammatory complications awaiting hematopoietic stem cell transplantation.

Effectiveness of ambulation to prevent venous thromboembolism in patients admitted to hospital: a systematic review.

Patient ambulation is frequently recommended to help prevent venous thromboembolism during hospital admission. Our objective was to synthesize the evidence for ambulation as a prophylaxis for venous thromboembolism in hospital. We conducted a systematic review. We searched MEDLINE, Embase, Scopus, Web of Science and Cochrane Central Register of Controlled Trials indexed from their inception through April 2020 for studies of adult patients admitted to hospital, in which ambulation or mobilization alone or concomitant with prophylaxis was indicated for prevention of venous thromboembolism. We searched ClinicalTrials.gov for unpublished trials. We included randomized controlled trials (RCTs) and observational studies. Two reviewers independently screened articles and assessed risk of bias using 2 validated tools. We scored studies on quality of reporting, internal and external validity and study power; combined scores determined the overall quality. Eighteen articles met the inclusion criteria: 8 retrospective and 2 prospective cohorts, 7 RCTs and 1 secondary analysis of an RCT. The intervention (ambulation or mobilized) groups varied across studies. Five studies examined exercise as a therapeutic prophylaxis for thrombosis and 9 described an ambulation protocol. Five studies attempted to quantify amount and duration of patient ambulation and 3 reported ambulation distance. In the 5 studies rated as good or excellent statistical quality, findings were mixed. Incidence of venous thromboembolism was lowest when pharmacologic anticoagulants were added as part of the prescribed prophylaxis regimen. We did not find high-quality evidence supporting ambulation alone as an effective prophylaxis for venous thromboembolism. Ambulation should not be considered an adequate prophylaxis for venous thromboembolism, nor as an adequate reason to discontinue pharmacologic prophylaxis for venous thromboembolism during a patient's hospital admission.

How well are patients with inflammatory rheumatic diseases protected against measles?

HintergrundPatienten mit entzündlich rheumatischen Erkrankungen haben aufgrund ihrer Autoimmunerkrankung, aber auch bedingt durch die immunsuppressive Medikation ein erhöhtes Infektrisiko. Obwohl Impfungen in der Primärprophylaxe von Infektionen bekanntermaßen effektiv sind, ist die Impfrate in Deutschland generell zu niedrig. Wegen des zuletzt zunehmenden, teils epidemieartigen Auftretens von Masern ist die Lebendimpfung gegen Masern in Deutschland seit Kurzem gesetzlich vorgeschrieben.FragestellungWie viele Patienten mit entzündlich rheumatischen Erkrankungen sind aktuell ausreichend gegen Masern geschützt?MethodePatienten mit entzündlich rheumatischen Erkrankungen des Rheumazentrums Ruhrgebiet wurden zwischen Dezember 2017 und Oktober 2018 prospektiv und konsekutiv eingeschlossen. Dabei wurden Daten zu Erkrankung und Therapie auf Ebene von Substanzklassen sowie die Impf- und Infektanamnese erhoben. Alle Angaben zu Impfungen wurden im Impfpass kontrolliert. Antikörpertiter gegen Masern wurden mit ELISA bestimmt. Als Schwellenwert für einen ausreichenden Schutz gegen Masern wurden 150 mIU/ml festgelegt.ErgebnisVon 975 Patienten konnten 540 (55,4 %) einen Impfausweis vorlegen. Bei 201 Patienten mit Ausweis (37,2 %) lagen dokumentierte Impfungen seit Geburt vor. Insgesamt hatten 45 von 267 nach 1970 geborene Patienten (16,9 %) einen suffizienten Impfschutz gegen Masern. Die anamnestischen Angaben zu einer Masernerkrankung in der Kindheit differenzierten nicht zwischen Patienten mit und ohne protektiven Masern-IgG-Antikörpern. Protektive Masern-IgG-Antikörper wurden bei 901 Patienten von 928 Patienten mit Messung der Masern-IgG-Antikörperspiegel (97,1 %) nachgewiesen. Die unterschiedlichen Wirkprinzipien der aktuellen immunsuppressiven Therapie hatten darauf keinen Einfluss.DiskussionDiese Daten zeigen, dass mindestens 2,9 % der Patienten keinen ausreichenden Schutz gegen Masern haben. Interessanterweise hatte die Mehrheit der nach 1970 geborenen Patienten protektive Antikörper trotz fehlenden Impfschutzes gegen Masern. Die Anstrengungen sowohl im primär- als auch im fachärztlichen Bereich sollten dringend verstärkt werden, um eine adäquate Infektionsprophylaxe bei besonders gefährdeten Patienten gewährleisten zu können.

HIV and lymphoma: from oncological futility to treatment

Cancer and HIV have been inextricably linked since the first report in 1982 of biopsy-confirmed Kaposi's sarcoma among previously healthy homosexual men living in Los Angeles and Orange counties, California, USA. 1 Centers for Disease ControlA cluster of Kaposi's sarcoma and pneumocystis carinii pneumonia among homosexual male residents of Los Angeles and Orange counties, California. MMWR Morb Mortal Wkly Rep. 1982; 31: 305-307 PubMed Google Scholar The cases established concerns for what later would be defined as AIDS. The report speculated: “One hypothesis consistent with the observations reported here is that infectious agents are being sexually transmitted among homosexually active males. Infectious agents not yet identified may cause the acquired cellular immunodeficiency that appears to underlie KS [Kaposi's sarcoma] and/or PCP [Pneumocystis carcinii pneumonia] among homosexual males.” The discovery of HIV proved it to be the aetiological agent. Given the known association between immunodeficiency and cancer and oncogenic virus and cancer, the discovery of human herpesvirus 8 (also known as Kaposi's sarcoma-associated herpesvirus) completed the puzzle on the mysterious outbreak of Kaposi's sarcoma. 2 Chang Y Cesarman E Pessin MS et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994; 266: 1865-1869 Crossref PubMed Scopus (4973) Google Scholar Epidemiology of haematological malignancies in people living with HIVPeople living with HIV or AIDS are at increased risk of Hodgkin and non-Hodgkin lymphoma compared with HIV-negative individuals. Data on the risk of multiple myeloma or leukaemia are inconsistent and of low quality but the risk does not seem to be increased. Specific haematological malignancies occur in different contexts of age, CD4 cell count, HIV control, viral co-infections, or chronic inflammation, and the expansion of combination antiretroviral therapy has led to varied demographic and epidemiological shifts among people with HIV. Full-Text PDF CAR T-cell therapy for cancer and HIV through novel approaches to HIV-associated haematological malignanciesPeople living with HIV are a global population with increased cancer risk but their access to modern immunotherapies for cancer treatment has been limited by socioeconomic factors and inadequate research to support safety and efficacy in this population. These immunotherapies include immune checkpoint inhibitors and advances in cellular immunotherapy, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite the field of cancer immunotherapy rapidly expanding with ongoing clinical trials, people with HIV are often excluded from such trials. Full-Text PDF Haemopoietic cell transplantation in patients living with HIVHaemopoietic cell transplantation is established as a standard treatment approach for people living with HIV who have haematological malignancies with poor prognosis. Studies with autologous and allogeneic haemopoietic cell transplantation suggest that HIV status does not adversely affect outcomes, provided that there is adequate infection prophylaxis. Attention to possible drug–drug interactions is important. Allogeneic haemopoietic cell transplantation substantially reduces the long-term HIV reservoir when complete donor chimerism is established. Full-Text PDF Treatment management of haematological malignancies in people living with HIVAlthough the incidence of HIV-associated lymphomas decreased after the introduction of effective combination antiretroviral therapy, they became the most common AIDS-related cancer in high-income countries. Moreover, as people living with HIV live longer, a wide range of non-AIDS-related cancer has emerged, including other haematological malignancies. Nonetheless, combination antiretroviral therapy has offered people with HIV the opportunity to receive the same therapies as those provided to the general population, and intensive curative therapies have become the standard. Full-Text PDF

Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics

Control of helminth parasites is a key challenge for human and veterinary medicine. In the absence of effective vaccines and adequate sanitation, prophylaxis and treatment commonly rely upon anthelmintics. There are concerns about the development of drug resistance, side-effects, lack of efficacy and cost-effectiveness that drive the need for new classes of anthelmintics. Despite this need, only three new drug classes have reached the animal market since 2000 and no new classes of anthelmintic have been approved for human use. So where are all the anthelmintics? What are the barriers to anthelmintic discovery, and what emerging opportunities can be used to address this? This was a discussion group focus at the 2019 8th Consortium for Anthelmintic Resistance and Susceptibility (CARS) in Wisconsin, USA. Here we report the findings of the group in the broader context of the human and veterinary anthelmintic discovery pipeline, highlighting challenges unique to antiparasitic drug discovery. We comment on why the development of novel anthelmintics has been so rare. Further, we discuss potential opportunities for drug development moving into the 21st Century.

Two novel risk factors for postoperative venous thromboembolism: A reconsideration of standard risk assessment and prophylaxis

BackgroundPostoperative venous thromboembolism (VTE) is usually preventable with adequate prophylaxis. In an institutional study, patients with emergency operations (EO), multiple operations (MO), and perioperative sepsis (PS) were more likely to develop VTE despite standard prophylaxis. MethodsGeneral surgery patients in the NSQIP database from 2011 to 2014 were stratified into VTE and non-VTE groups, and statistical analyses were performed. ResultsAmong 1,610,086 patients, 13,673 (0.8%) were diagnosed with VTE. The VTE odds ratios for patients with EO, MO and PS were 1.4 (95%CI:1.3–1.5), 1.9 (95%CI:1.7–2.0), and 2.4 (95%CI:2.2–2.5), respectively. VTE odds ratios increased with concurrence of two factors (EO+PS: 2.0 (95%CI:1.9–2.2)) (EO+MO: 2.3 (95%CI:1.9–2.7)) (MO+PS: 2.5 (95%CI:2.2–2.7)) and further still for patients with all three factors (2.7, 95%CI:2.4–3.0). ConclusionGeneral surgery patients with EO, MO, or PS have a greater likelihood of developing postoperative VTE. These factors are not necessarily captured in contemporary risk assessment models that guide chemoprophylaxis, and so these high-risk patients may receive insufficient prophylaxis.

A Care Bundle Intervention to Prevent Surgical Site Infections After a Craniotomy.

Although surgical site infections after a craniotomy (SSI-CRANs) are a serious problem that involves significant morbidity and costs, information on their prevention is scarce. We aimed to determine whether the implementation of a care bundle was effective in preventing SSI-CRANs. A historical control study was used to evaluate the care bundle, which included a preoperative shower with 4% chlorhexidine soap, appropriate hair removal, adequate preoperative systemic antibiotic prophylaxis, the administration of 1 g of vancomycin powder into the subgaleal space before closing, and a postoperative dressing of the incisional surgical wound with a sterile absorbent cover. Patients were divided into 2 groups: preintervention (January 2013 to December 2015) and intervention (January 2016 to December 2017). The primary study end point was the incidence of SSI-CRANs within 1 year postsurgery. Propensity score matching was performed, and differences between the 2 study periods were assessed using Cox regression models. A total of 595 and 422 patients were included in the preintervention and intervention periods, respectively. The incidence of SSI-CRANs was lower in the intervention period (15.3% vs 3.5%; P < .001). Using a propensity score model, 421 pairs of patients were matched. The care bundle intervention was independently associated with a reduced incidence of SSI-CRANs (adjusted odds ratio, 0.23; 95% confidence interval, .13-.40; P < .001). The care bundle intervention was effective in reducing SSI-CRAN rates. The implementation of this multimodal preventive strategy should be considered in centers with high SSI-CRAN incidences.