Time to Disability Milestones and Annualized Relapse Rates in NMOSD and MOGAD.

OBJECTIVE: To investigate accumulation of disability in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) in a changing treatment landscape. We aimed to identify risk factors for the development of disability milestones in relation to disease duration, number of attacks, and age. METHODS: We analyzed data from individuals with NMOSD and MOGAD from the German Neuromyelitis Optica Study Group registry. Applying survival analyses, we estimated risk factors and computed time to disability milestones as defined by the Expanded Disability Status Score (EDSS). RESULTS: We included 483 patients: 298 AQP4-IgG+ NMOSD, 52 AQP4-IgG-/MOG-IgG- NMOSD patients, and 133 patients with MOGAD. Despite comparable annualized attack rates, disability milestones occurred earlier and after less attacks in NMOSD patients than MOGAD patients (median time to EDSS 3: AQP4-IgG+ NMOSD 7.7 (95% CI 6.6-9.6) years, AQP4-IgG-/MOG-IgG- NMOSD 8.7) years, MOGAD 14.1 (95% CI 10.4-27.6) years; EDSS 4: 11.9 (95% CI 9.7-14.7), 11.6 (95% lower CI 7.6) and 20.4 (95% lower CI 14.1) years; EDSS 6: 20.1 (95% CI 16.5-32.1), 20.7 (95% lower CI 11.6), and 37.3 (95% lower CI 29.4) years; and EDSS 7: 34.2 (95% lower CI 31.1) for AQP4-IgG+ NMOSD). Higher age at onset increased the risk for all disability milestones, while risk of disability decreased over time. INTERPRETATION: AQP4-IgG+ NMOSD, AQP4-IgG-/MOG-IgG- NMOSD, and MOGAD patients show distinctive relapse-associated disability progression, with MOGAD having a less severe disease course. Investigator-initiated research has led to increasing awareness and improved treatment strategies appearing to ameliorate disease outcomes for NMOSD and MOGAD. ANN NEUROL 2024;95:720-732.

Effects of team leaders' position in cardiopulmonary resuscitation teams on leadership behavior and team performance: A prospective randomized interventional cross-over simulation-based trial.

BACKGROUND: Leadership is an important performance factor in resuscitation teams. Medical guidelines for cardiopulmonary resuscitation (CPR) advise team leaders to keep hands off patients. There is little evidence for this recommendation that is based purely on observational data. Accordingly, the aim of this trial was to investigate the effect of leaders' position during CPR on leadership behavior and team performance. METHOD: This is a prospective randomized interventional crossover simulation-based single center trial. Teams of 3 to 4 physicians each, representing a rapid response team, were confronted with a simulated cardiac arrest. Team leaders were randomly assigned and assigned team leaders were 1:1 randomized to 2 leadership positions: position at the patient's head; and hands-off position. Data analysis was performed from video-recordings. All utterances during the first 4 minutes of CPR were transcribed and coded based on a modified "Leadership Description Questionnaire." The primary endpoint was the number of leadership statements. Secondary outcomes included CPR related performance markers like hands-on time and chest compression rate, and the behavioral related endpoints Decision Making, Error Detection, and Situational Awareness. RESULTS: Data from 40 teams (143 participants) was analyzed. Leaders in hands-off position made more leadership statements (28 ± 8 vs 23 ± 8; P <.01) and contributed more to their team's leadership (59 ± 13% vs 50 ± 17%; P = .01) than leaders in the head position. Leaders' position had no significant effect on their teams' CPR performance, Decision Making, and Error Detection. Increased numbers of leadership statements lead to improved hands-on time ( R = 0.28; 95% confidence interval 0.05-0.48; P = .02). CONCLUSIONS: Team leaders in a hands-off position made more leadership statements and contributed more to their teams' leadership during CPR than team leaders actively involved in the head position. However, team leaders' position had no effect on their teams' CPR performance.

High species diversity of Echinococcus spp. in wild mammals of Namibia.

An opportunistic survey for Echinococcus spp. in wild mammals was conducted in seven distinct study areas throughout Namibia, representing all major ecosystems, between 2012 and 2021. In total, 184 individually attributable faeces and 40 intestines were collected from eight species of carnivores, and 300 carcasses or organs of thirteen species of ungulates were examined for Echinococcus cysts. Nested PCR and sequencing of the mitochondrial nad1 gene led to the identification of five species of the Echinococcus granulosus sensu lato complex. Echinococcus canadensis G6/7 was found throughout Namibia at low frequency in lions, cheetahs, African wild dogs, black-backed jackals and oryx antelopes. Echinococcus equinus was present only in northern Namibia, locally at high frequency in lions, black-backed jackals and plains zebras. Echinococcus felidis was found only in one small area in the north-east of Namibia, but with high frequency in lions and warthogs. Echinococcus granulosus sensu stricto was identified only in two African wild dogs in the north-east of Namibia, and Echinococcus ortleppi occurred in central and southern Namibia in black-backed jackals and oryx antelopes. The development of fertile cysts indicated active intermediate host roles of oryx antelopes for E. canadensis and E. ortleppi, of warthogs for E. felidis, and of plains zebras for E. equinus. Our data support earlier hypotheses of exclusive or predominant wildlife life-cycles for E. felidis involving lions and warthogs, and - in Namibia - for E. equinus involving lions and/or black-backed jackals and plains zebras. Our data further support an interlink of wild and domestic transmission for E. ortleppi. A possible involvement of livestock and domestic dogs in transmission of E. canadensis G6/7 and E. granulosus s.s., the two parasite species with highest zoonotic potential, is uncertain for Namibia and needs further investigation.

Cystic echinococcosis in donkeys in eastern Africa.

Cystic echinococcosis (CE) is endemic in humans and domestic animals in eastern Africa. All the species of the Echinococcus granulosus sensu lato complex have been reported in this region except for E. equinus, possibly due to the small number of studies involving equids. This study reports the frequency of different Echinococcus species in donkeys from eastern Africa. A total of 5961 donkeys were examined during meat inspection in 3 slaughterhouses in Kenya. Identification of Echinococcus spp. was achieved through polymerase chain reaction-restriction fragment-length polymorphism and sequencing of the mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 gene. The prevalence of CE was 5.7% (337/5961). The 263 genotyped cysts belonged to E. equinus (n = 163), E. granulosus sensu stricto (n = 70), E. canadensis (G6/7) (n = 26) and E. ortleppi (n = 4). One donkey harboured a metacestode of Spirometra theileri. All E. equinus cases, except 2, originated from southern Ethiopia, whereas the other species were more evenly distributed across the study area. Most of the cysts belonging to E. equinus were fertile (111/163), while those of the other species were non-fertile. This is the first report of Echinococcus spp. in donkeys from sub-Saharan Africa and the first confirmation of E. equinus in East Africa. The frequent fertility of E. equinus cysts in donkeys affirms their suitability as intermediate hosts of this species, while low frequency and cyst fertility suggest a marginal role of donkeys in the transmission of E. granulosus s. s., E. canadensis (G6/7) and E. ortleppi.

Cystic echinococcosis of ruminant livestock in Namibia.

Cystic echinococcosis (CE) is widespread and locally frequent in southern Africa where it affects humans, livestock, and wild mammals. However, most data from the region are old and do not provide information on the causative Echinococcus species. For Namibian livestock only anecdotal records were available prior to this preliminary survey. Our retrospective analysis of slaughterhouse records of CE in cattle from the commercial farming area in central and southern Namibia resulted in 1.65% CE prevalence among 35,143 slaughtered cattle in the period 2015-2016. For comparison, carcasses of ruminant livestock were prospectively examined in the communal farming areas of northern Namibia, resulting in three CE cases among only 12 cattle, and no cases among nine goats. To determine the Echinococcus species affecting Namibian livestock, a total of 53 cysts were collected from all parts of the country and analysed for species and genotype by amplification and sequencing of the nad1 gene. All 50 cattle cysts (isolated from 40 cattle), both from the commercial and communal farming areas, were Echinococcus ortleppi (all fertile, and 42/50 from the lungs), while three opportunistically collected cysts from three sheep in southern Namibia were E. canadensis G7. Our data suggest that E. ortleppi is the only CE agent that is relevant for cattle infection in Namibia, and that low prevalence in the commercial farming areas contrasts with high CE burden in the northern traditional husbandry systems. The present data provide baseline information to stimulate epidemiological studies on the transmission pathways of various CE agents in livestock, wildlife, and humans in Namibia and neighbouring countries.

Echinococcus multilocularis specific antibody, systemic cytokine, and chemokine levels, as well as antigen-specific cellular responses in patients with progressive, stable, and cured alveolar echinococcosis: A 10-year follow-up.

BACKGROUND: The infestation with Echinococcus multilocularis larvae may persist in humans for up to decades without evident clinical symptoms. Longitudinal investigations are needed to understand the dynamic immunological processes in alveolar echinococcosis (AE) patients associated with an active and progressive, a stable or a regressive course of disease. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluated the E. multilocularis specific antibody responses, systemic cytokine, and chemokine serum levels over a 10-year follow-up period, as well as cellular responsiveness in AE patients. Our results demonstrate a rapid decrease in antibodies against E. multilocularis specific antigen Em2+. Especially in cured patients, these antibodies remained negative, making them a significant predictor for cured AE. E. multilocularis specific IgG4, and indirect hemagglutination IHA decreased later in time, after around 5 years. While total IgE did not show significant dynamics over the course of disease, E. multilocularis specific IgE decreased after one to two years, and increasing levels were a significant predictor of progressive disease. There was no significant change in systemic IL-8, IL-9, CCL18 or CCL20 serum levels over time. Univariate analysis across groups indicated lower IL-8 levels in cured patients; however, this result could not be confirmed by multivariate analysis. Levels of CCL17 decreased during treatment, especially in cured patients, and thus might serve as a predictive or risk factor for progressive disease. Levels of IL-10 and CCL13 decreased during disease, especially after five and ten years of intervention. The E. multilocularis antigen (EmAg) inducible cellular productions of MCP1(CCL13), TARC(CCL17) and PARC(CCL18) were lowest in patients with cured AE and infection-free controls, while the EmAg inducible cellular production of IFN-γ increased after cure. Significant positive cytokine and chemokine correlations were observed in AE patients for IL-9, IL-10, CCL13(MCP-4), CCL17(TARC) and CCL20(LARC)(for all p<0.001). E. multilocularis specific IgG4 response correlated positively with TARC (p<0.001). Both markers enhanced over time in progressive disease and decreased after cure. The levels of IL-8, IL-10, MCP4 and LARC enhanced with AE regression. CONCLUSIONS/SIGNIFICANCE: Repeated biomarker surveys are advisable to evaluate progression or regression of disease during longitudinal follow-up and such analyses can support imaging techniques and improve staging of AE patients.

Advances in the treatment, diagnosis, control and scientific understanding of taeniid cestode parasite infections over the past 50 years.

In the past 50 years, enormous progress has been made in the diagnosis, treatment and control of taeniid cestode infections/diseases and in the scientific understanding thereof. Most interest in this group of parasites stems from the serious diseases that they cause in humans. It is through this lens that we summarize here the most important breakthroughs that have made a difference to the treatment of human diseases caused by these parasites, reduction in transmission of the taeniid species associated with human disease, or understanding of the parasites' biology likely to impact diagnosis or treatment in the foreseeable future. Key topics discussed are the introduction of anti-cestode drugs, including benzimidazoles and praziquantel, and the development of new imaging modalities that have transformed the diagnosis and post-treatment monitoring of human echinococcoses and neurocysticercosis. The availability of new anti-cestode drugs for use in dogs and a detailed understanding of the transmission dynamics of Echinococcus granulosus sensu lato have underpinned successful programs that have eliminated cystic echinococcosis in some areas of the world and greatly reduced the incidence of infection in others. Despite these successes, cystic and alveolar echinococcosis and neurocysticercosis continue to be prevalent in many parts of the world, requiring new or renewed efforts to prevent the associated taeniid infections. Major advances made in the development of practical vaccines against E. granulosus and Taenia solium will hopefully assist in this endeavour, as might the understanding of the parasites' biology that have come from an elucidation of the nuclear genomes of each of the most important taeniid species causing human diseases.

Human Cord Blood B Cells Differ from the Adult Counterpart by Conserved Ig Repertoires and Accelerated Response Dynamics.

Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics.

Evaluation of dried blood spots as alternative sampling material for serological detection of anti-SARS-CoV-2 antibodies using established ELISAs.

OBJECTIVES: During the current pandemic, antibody testing based on venous serum helps to determine whether the tested person has been previously infected with SARS-CoV-2. Alternatively, capillary blood can be taken via a finger prick (dried blood spots, DBS). In this study, paired DBS and venipuncture samples were tested using two serological assays to evaluate the usability of DBS for the detection of anti-SARS-CoV-2 antibodies. METHODS: Paired samples of DBS and venous serum were collected from 389 volunteers, of whom 75 had a recent PCR-confirmed SARS-CoV-2 infection, and tested for anti-SARS-CoV-2 IgG antibodies against both viral S1 and nucleocapsid protein (NCP) antigens using two ELISAs. Degree of agreement and correlation coefficients between ELISA results based on the two sampling methods were calculated. RESULTS: Results of DBS showed almost perfect agreement and high correlations with results from corresponding serum samples in both the S1-based ELISA and the NCP-based ELISA. CONCLUSIONS: ELISA results derived from DBS showed very high agreement to those obtained with serum, supposing adequate usability and robustness of DBS as sample material for detection of anti-SARS-CoV-2 antibodies. In the near future, large-scale epidemiological screening for antibodies against SARS-CoV-2 will be carried out. Since DBS reduce the strain on healthcare institutions regarding sample collection, they have a potential to facilitate efficient community- and population-based screening in the current SARS-CoV-2 pandemic.

Cancer and Immune Checkpoint Inhibitor Treatment in the Era of SARS-CoV-2 Infection.

Whether cancer patients receiving immune checkpoint inhibitors (ICI) are at an increased risk of severe infection and mortality during the corona pandemic is a hotly debated topic that will continue to evolve. Here, we summarize and discuss current studies regarding COVID-19 and anti-cancer treatment with an emphasis on ICI. Importantly, several lines of evidence suggest that patients currently treated with ICI do not display an increased vulnerability to infection with SARS-CoV-2. Data regarding morbidity and mortality associated with COVID-19 in cancer patients receiving ICI are less clear and often conflicting. Although mostly based on experimental data, it is possible that ICI can promote the exacerbated immune response associated with adverse outcome in COVID-19 patients. On the other hand, mounting evidence suggests that ICI might even be useful in the treatment of viral infections by preventing or ameliorating T cell exhaustion. In this context, the right timing of treatment might be essential. Nevertheless, some cancer patients treated with ICI experience autoimmune-related side effects that require the use of immunosuppressive therapies, which in turn may promote a severe course of infection with SARS-CoV-2. Although there is clear evidence that withholding ICI will have more serious consequences, further studies are urgently needed in to better evaluate the effects of ICI in patients with COVID-19 and the use of ICI during the corona pandemic in general.

STAT1 deficiency predisposes to spontaneous otitis media.

Signal transducer and activator of transcription 1 (STAT1) is known to be an important player in inflammatory responses. STAT1 as a transcription factor regulates the expression of multiple proinflammatory genes. Inflammatory response is one of the common effects of ototoxicity. Our group reported that hair cells of STAT1 knockout (STAT1-KO) mice are less sensitive to ototoxic agents in-vitro. The effect of inflammatory responses in STAT1-KO mice has primarily been studied challenging them with several pathogens and analyzing different organs of those mice. However, the effect of STAT1 ablation in the mouse inner ear has not been reported. Therefore, we evaluated the cochlear function of wild type and STAT1-KO mice via auditory brain stem response (ABR) and performed histopathologic analysis of their temporal bones. We found ABR responses were affected in STAT1-KO mice with cases of bilateral and unilateral hearing impairment. Histopathologic examination of the middle and inner ears showed bilateral and unilateral otitis media. Otitis media was characterized by effusion of middle and inner ear that varied between the mice in volume and inflammatory cell content. In addition, the thickness of the middle ear mucosae in STAT1-KO mice were more pronounced than those in wild type mice. The degree of middle and inner ear inflammation correlated with ABR threshold elevation in STAT1-KO mice. It appears that a number of mice with inflammation underwent spontaneous resolution. The ABR thresholds were variable and showed a tendency to increase in homozygous and heterozygous STAT1-KO mice. These findings suggest that STAT1 ablation confers an increased susceptibility to otitis media leading to hearing impairment. Thus, the study supports the new role of STAT1 as otitis media predisposition gene.

Combining Computed Tomography and Histology Leads to an Evolutionary Concept of Hepatic Alveolar Echinococcosis.

Alveolar echinococcosis (AE) is caused by the intermediate stage of Echinococcus multilocularis. We aimed to correlate computed tomography (CT) data with histology to identify distinct characteristics for different lesion types. We classified 45 samples into five types with the Echinococcus multilocularis Ulm Classification for Computed Tomography (EMUC-CT). The various CT lesions exhibited significantly different histological parameters, which led us to propose a progression model. The initial lesion fit the CT type IV classification, which comprises a single necrotic area with the central located laminated layer, a larger distance between laminated layer and border zone, a small fibrotic peripheral zone, and few small particles of Echinococcus multilocularis (spems). Lesions could progress through CT types I, II, and III, characterized by shorter distances between laminated layer and border zone, more spems inside and surrounding the lesion, and a pronounced fibrotic rim (mostly in type III). Alternatively, lesions could converge to a highly calcified, regressive state (type V). Our results suggest that the CT types mark sequential stages of the infection, which progress over time. These distinct histological patterns advance the understanding of interactions between AE and human host; moreover, they might become prognostically and therapeutically relevant.

Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review.

BACKGROUND: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). MATERIALS AND METHODS: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and/or incidence of EC among women using MHT. RESULTS: 31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10/19 studies with odds ratios (ORs)/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (≥10 years), not confirmed in three other sub-group analyses of women with ≥6, ≥5, and >10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6/12 studies with ORs/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. CONCLUSION: ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.

Echinococcus ortleppi and Echinococcus canadensis G6/7 affect domestic animals in western Zambia.

Cystic echinococcosis (CE) is endemic in many parts of sub-Saharan Africa. In contrast to the eastern part of the continent, very little data exists on the current disease situation in southern Africa including Zambia. This study determined frequency and species identity of Echinococcus spp. circulating in livestock and dogs in the Western Province of Zambia. Cysts were collected in slaughterhouses at meat inspection (cattle) and during examination of home slaughtered pigs, while dog faecal samples were collected per-rectum and examined microscopically for the presence of taeniid eggs. Individual taeniid eggs from faecal samples and individual protoscoleces from cysts were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or sequencing of the NADH-dehydrogenase subunit 1 (nad1) and cytochrome C oxidase 1 (cox1) gene. Fifty-four of 2000 cattle (2.7%) were found infected with a total of 65 cysts, predominantly fertile lungs cysts; all cysts were identified as Echinococcus ortleppi. Two out of 52 home-slaughtered pigs (3.8%) were infected with a fertile lung cyst each; both cysts were also identified as E. ortleppi. Microscopic examination revealed 10/289 dog faecal samples to contain taeniid eggs, of which four samples (two each) contained Echinococcus canadensis (G6/7) or Taenia hydatigena, respectively. This is the first insight in the Echinococcus species circulating in Zambia providing premises for further studies into transmission dynamics of CE in the southern African region.

Diversity of Taenia and Hydatigera (Cestoda: Taeniidae) in domestic dogs in Kenya.

Taenia species of domestic dogs can cause cysticercosis and coenurosis in a wide range of intermediate hosts including humans. Most taeniids of dogs are globally distributed, but some wildlife-transmitted species can be specific for certain regions. Generally, little information exists on the species composition and frequency in most regions of the world, which impairs risk assessment and control strategies. This study determined the range of taeniid species in dogs in four widely spaced areas of Kenya by genetic identification of eggs in faeces collected from the environment. Individual taeniid eggs were characterised by nested polymerase chain reaction of NADH dehydrogenase subunit 1 and cytochrome C oxidase 1 genes, restriction fragment length polymorphism and partial sequencing. Overall 79/1621 (4.9%) faecal samples contained eggs of Taenia or Hydatigera (8.0% in Turkana, 4.8% in Isiolo, 3.8% in Maasai Mara and 1.3% in Meru). Taenia hydatigena and T. multiceps were the most frequent, found in 36 and 15 samples, respectively. Other eggs found in the faeces belonged to T. serialis (sensu lato), T. madoquae (the first record in domestic dogs), T. ovis, T. saginata and Hydatigera taeniaeformis. Polymorphism of nad1 sequences revealed 22 and 8 haplotypes of T. hydatigena and T. multiceps, respectively. The results show the involvement of dogs in both domestic and sylvatic transmission cycles. In addition to the species range, this study provides data on the intraspecific diversity of T. hydatigena and T. multiceps in Kenya, which will serve as baseline information for further studies into cysticercosis and coenurosis in livestock and humans in the region.

Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay.

The majority of congenital cytomegalovirus (cCMV) infections are asymptomatic at birth and therefore not diagnosed. Approximately 10-15% of these infants develop late-onset hearing loss and other developmental disorders. Implementation of a universal screening approach at birth may allow early initiation of symptomatic interventions due to a closer follow-up of infants at risk and offers the opportunity to consider treatment of late-onset disease. Real-time PCR assays for the detection of CMV DNA in buccal swab samples demonstrated feasibility and good clinical sensitivity in comparison to a rapid culture screening assay. Because most cCMV infections remain asymptomatic, a universal screening assay that stratifies CMV infected infants according to low and high risk of late-onset cCMV disease could limit the parental anxiety and reduce follow-up costs. We therefore developed and characterized a screening algorithm based on a highly-sensitive quantitative real-time PCR assay that is compatible with centralized testing of samples from universal screening and allows to determine CMV DNA load of saliva samples either as International Units (IU)/ml saliva or IU/105 cell equivalents. 18 of 34 saliva samples of newborns that tested positively by the screening algorithm were confirmed by detection of CMV DNA in blood and/or urine samples obtained during the first weeks of life. All screening samples that could not be confirmed had viral loads of <2.3x105 IU/ml saliva (median: 6.8x103) or 1.3x105 IU/105 cell equivalents (median: 4.0x102). The viral load of screening samples with confirmed cCMV infection ranged from 7.5x102 to 8.2x109 IU/ml saliva (median: 9.3x107) or 1.5x102 to 5.6x1010 IU/105 cell equivalents (median: 3.5x106). Clinical follow-up of these newborns with confirmed cCMV infection should reveal whether the risk of late-onset cCMV disease correlates with CMV DNA load in early life saliva samples and whether a cut-off can be defined identifying cCMV infected infants with or without risk for late-onset cCMV disease.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for endometrial cancer-derived peritoneal metastases: a systematic review.

Cytoreductive surgery (CRS) is an appropriate treatment for selected patients with endometrial cancer (EC)-derived peritoneal metastases (PM). Hyperthermic intraperitoneal chemotherapy (HIPEC) may enhance the therapeutic efficacy of CRS in these patients. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials and case reports reporting on the safety and efficacy of CRS and HIPEC in patients with EC-derived PM. Eight publications reporting on 68 patients were identified. The mean patient age was 57.1 years and the mean time from initial treatment of EC to CRS and HIPEC was 22.3 months. 41/64 patients had adenocarcinomas, type II cancers were present in 23/64 patients. The mean peritoneal carcinomatosis index (PCI) was 16.7. A complete surgical resection CC-0 was achieved in 44/63 (70%) patients. The chemotherapy regimens used for HIPEC were variable, but all included cisplatin, administered either alone (39/68 patients) or combined with doxorubicin or paclitaxel or mitomycin (29/68 patients). The duration of HIPEC was 60 min in 51/68 patients and 90 min in 17/68 patients. Mostly, the closed technique was used (55/68 patients). Adverse events grades 1/2, 3, and 4 were observed in 23/63, 12/63, and 6/63 patients, respectively. Treatment-associated mortality was 1% (1/63). After CRS and HIPEC, most patients received systemic chemotherapy (46/63 patients). Median disease-free and overall survival ranged from 7 to 18 and 12 to 33 months, respectively. In conclusion, CRS and HIPEC in EC with PM is safe and feasible. An additional therapeutic value of HIPEC is suggested, but prospective comparative trials are warranted.

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.

A novel bispecific antibody format was applied to generate T cell-engaging antibodies. The TriFab format is a trivalent IgG-shaped entity composed of two Fab arms that bind to antigens on the surface of tumor cells, which are linked via flexible peptides to a CD3 binding moiety that replaces the CH2 domains of conventional IgGs. The distinctive feature of these T cell recruiting bispecifics is that their CD3 variable regions are incorporated between domains, rather than N- or C-terminally fused to an Fc or antibody fragments. T cell recruiting TriFabs resemble in size and shape, are expressed and show biophysical properties similar to regular IgGs. Transmission electron microscopy (TEM) demonstrates high flexibility of the cell surface binding arms as well as target antigen accessibility of the interspersed CD3 binding domain. Functional co-culturing assays of peripheral blood mononuclear cells (PBMCs) and different tumor cell lines (MCF7 and A431) revealed a dose-dependent T cell-mediated cytotoxicity that was induced by the TriFabs targeting either LeY or EGFR cell surface antigens.

Molecular characterization of Echinococcus species in dogs from four regions of Kenya.

Cystic echinococcosis is endemic both in livestock and humans in many parts of Kenya. However, very little data exists on Echinococcus infections in dogs, and therefore their role in maintaining the transmission cycles and environmental contamination with eggs of Echinococcus species is unknown. The study aimed to establish the prevalence and distribution of Echinococcus granulosus sensu lato causing infection in dogs in Kenya. A total of 1621 dog faecal samples were collected from the environment in four different regions and examined microscopically for the presence of taeniid eggs. Up to 20 individual taeniid eggs per faecal sample were picked, lysed and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing of the NADH dehydrogenase subunit 1 (nad1) gene. Eleven percent (178/1621) of faecal samples had taeniid eggs, while 4.4% (71/1621) contained Echinococcus spp. eggs. Area-wise, the faecal prevalence of Echinococcus spp. was 9.2% (48/524) in Turkana, 4.0% (20/500) in Maasai Mara, 0.7% (2/294) in Isiolo and 0.3% (1/303) in Meru. E. granulosus sensu stricto (s. s.) was the dominant Echinococcus taxon, followed by E. canadensis (G6/7) that was detected in 51 and 23 faecal samples, respectively. E. ortleppi was detected in only 5 faecal samples. We report for the first time the presence of E. felidis eggs in two dog faecal samples (from Maasai Mara region). Mixed infections of these taxa were also found in faecal samples, including: E. granulosus s. s. and E. canadensis (G6/7) (n = 7), E. granulosus s. s. and E. ortleppi (n = 1) and all three species (n = 1). The dog data presented here confirm the differences in diversity and abundance of Echinococcus spp. between regions of Kenya, correspond well with previously published data from livestock, and tentatively suggest a role of domestic dogs as a link between domestic and sylvatic cycles of Echinococcus spp.