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Introduction:Germ cell tumors (GCTs) are the most common type of cancer in adolescent and young adult males. Most of them are curable with multimodal treatment: platinum-based chemotherapy (CT) + surgery. Patients who fail first-line treatment usually receive salvage CT with response rates between 30 and 50%. High-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT) is an effective treatment in this context. Methods: We conducted a multicenter retrospective analysis of patients ≥ 15 years old with relapsed/refractory GCTs who received HDCT in 13 centers of the Argentine Group of Bone Marrow Transplantation and Cellular Therapy (GATMO-TC) from 2010 to 2022. Results: 114 patients were included, with a median age of 32 years (range: 15-58). Most had non-seminoma histology (66%); The primary tumor site was testis (65%), retroperitoneum (17%) and mediastinum (9%). Forty percent (n:46) had unfavorable prognosis according to the IGCCCG score. Eighty-two % received ≥ 2 lines of CT before HDCT, 27% being platinum refractory disease (PRD); and 45% received 2 consecutive course of HDCT (tandem) All patients received carboplatin-etoposide based conditioning regimen. The median engraftment time was 12 days (d) (r8;25) for neutrophils and 15 d (r6;58) for platelets. Bacteremia (25%) and Hepatotoxicity (14.9%) were the most frequent G3-4 adverse event. With a median follow up of 12.6 months (r1-138), 100 pts were evaluable for survival. 12- and 24-months OS was 67%- 64%; and PFS 56%; - 54% respectively. PRD patients had worse OS and PFS. Eighteen patients remained alive and without relapsed beyond 5 years of follow up. Table 1: OS and PFS according to 1stline response. Conclusions: This real world multicentric study demonstrates that patients with refractory/relapsed metastatic GCT are curable by HDCT, being an effective and safe feasible treatment with response rates similar to those described in the literature. Superiority of the tandem approach could not be demonstrated due to the heterogeneity of the sample.

Post-transplant cyclophosphamide (PTCy) is an established platform for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). A study by CIBMTR demonstrated that it is associated with a higher incidence of cytomegalovirus infection (CMVi), regardless of the donor type. Primary prophylaxis (PP) with letermovir (L) has shown benefits in reducing the rate of CMVi.

The rabbit tick, Haemaphysalis leporispalustrisPackard, is known for its association with Rickettsia rickettsiias it harbors both virulent and avirulent strains of this pathogen. In this manuscript we report findings and preliminary characterization of a novel spotted fever group rickettsia (SFGR) in rabbit ticks from California, USA. Rickettsiasp. CA6269 (proposed “CandidatusRickettsia lanei”) is most related to known R. rickettsiiisolates but belongs to its own well-supported branch different from those of all R. rickettsiiincluding strain Hlp2 and from Rickettsiasp. 364D (also known as R. philipii) and R. peacockii.This SFGR probably exhibits both transovarial and transstadial survival since it was found in both questing larvae and nymphs. Although this rabbit tick does not frequently bite humans, its role in maintenance of other rickettsial agents and this novel SFGR warrant further investigation.

Consolidation with autologous stem cell transplant (ASCT) in Hodgkin lymphoma (HL) was traditionally reserved for patients with chemosensitive disease. In 2021 a retrospective study showed encouraging results with ASCT consolidation after checkpoint inhibitors (CPI) in pts with relapsed/refractory (R/R) HL. Subsequently, several prospective studies with CPI +/- chemotherapy in 2nd line were published showing 1-year progression free survival (1-y PFS) rates of 90% but with increased incidence of engrafment syndrome.

Seasonal activity patterns of questing western black-legged ticks, Ixodes pacificuswere investigated in northwestern California. Adult I. pacificusbecame active in the fall (late October/early November) and their appearance was associated with the first rain of the season. Following a peak in January, the abundance of adult ticks declined such that they were rare or absent by June/July. The nymphal tick activity season occurred from January through October, and larval activity occurred from April to June, but sometimes extended into October. Thus, potentially infectious ticks (nymphs and adults) present a year-round risk of Lyme disease transmission in northwestern California. The seasonality of Lyme disease cases in humans, based on the onset of erythema migrans, mirrored tick activity patterns and was year-round in cases infected in California. Peak incidence in humans occurs from May through July, and indicates that most disease transmission is from nymphal ticks. This study demonstrates that tick activity patterns are more extended than previously recognized in northwestern California.

ABSTRACTDusky-footed wood rats (Neotoma fuscipes) andPeromyscussp. mice (P. maniculatusandP. truei) were collected from one site in Placer County, one site in Santa Cruz County, and two sites in Sonoma County in northern California. Serum or plasma samples from 260 rodents were tested for antibodies to the agent of human granulocytic ehrlichiosis. Of these, samples from 25 wood rats (34% of those tested) and 10 (8%)Peromyscussp. mice were found to be seropositive, but only those from one site. PCR assays targeting the groESLheat shock operon were conducted on all seropositive specimens and a subset of seronegative blood specimens. Ehrlichial DNA was identified in 17 (68%) of the 25 seropositive wood rat blood samples and in 1 of the 10 (10%) Peromyscussp. specimens. None of 40 seronegative blood samples was PCR positive. Both seropositive and PCR-positive animals were collected during each trapping period. One male tick out of 84 Ixodes pacificusadults collected was PCR positive; samples of Dermacentor occidentalisnymphs and adults were negative. Nucleotide sequences of amplicons from three wood rat blood specimens and from the single PCR-positive tick differed by one and two bases, respectively, from a sequence previously obtained fromEhrlichia equi. At one site in Sonoma County, wood rats had a concurrent high prevalence of seropositivity and PCR positivity, while other sigmodontine rodents collected at the site were only occasionally infected. We suggest that dusky-footed wood rats serve as reservoirs of granulocytic ehrlichial agents in certain areas of northern California. The tick species involved in the transmission of granulocytic ehrlichiae among wood rats remains unknown.

Primordial germ cells arise during gastrulation and migrate from the hindgut into the gonad primordium during early organogenesis. In this article, we discuss factors that control migration, proliferation and targeting of the PGCs. In particular we discuss how changes in adhesiveness control germ cell positioning in the gonad, and the molecules involved.

Cell migration is an essential component of embryogenesis. In order to move from one location to another, cells must quantitatively alter their adhesiveness to the different substrata they encounter. Little is known about these changes in adhesive strengths, nor how they are controlled. Here we describe a combination of simple, quantitative, and reproducible methods to partially purify primordial germ cells from different stages of early mouse embryos, and compare their strengths of adhesion to different extracellular matrix glycoproteins. Primordial germ cells arise very early in the mouse embryo, and migrate through the tissues of the embryo to reach the site of gonad formation. Here they assemble into sex cords and start to differentiate into male or female gametes. Although the focus here is germ line cells, in principle this method can be used on any population of cells in the early embryo.

Primordial germ cells (PGCs) are the founder cell population of the gametes which form during the sexually mature stage of the life cycle. In the mouse, they arise early in embryogenesis, first becoming visible in the extraembryonic mesoderm, posterior to the primitive streak, at 7.5 days post coitum (d.p.c.). They subsequently become incorporated into the epithelium of the hind gut, from which they emigrate (9.5 d.p.c.) and move first into the dorsal mesentery (10.5 d.p.c.), and then into the genital ridges that lie on the dorsal body wall (11.5 d.p.c.). We have used confocal microscopy to study PGCs stained with an antibody that reacts with a carbohydrate antigen (Stage-Specific Embryonic Antigen-1, SSEA-1) carried on the PGC surface. This allows the study of the whole PGC surface, at different stages of their migration. The appearance of PGCs in tissue sections has given rise to the conventional view that they migrate as individuals, each arriving in turn at the genital ridge. In this paper, we show that PGCs leave the hind gut independently, but then extend long (up to 40 μm) processes, with which they link up to each other to form extensive networks. During the 10.5 – 11.5 d.p.c. period, these networks of PGCs aggregate into groups of tightly apposed cells in the genital ridges. As this occurs, their processes are lost, and their appearance suggests they are now non-motile. Furthermore, we find that PGCs taken from the dorsal mesentery at 10.5 d.p.c. perform the same sequence of movements in culture. At first they are actively locomotory. They become linked to other PGCs via long processes and form clusters of non-motile cells. This aggregation together into closely apposed masses may be an important component of PGC migration from the gut into the genital ridges and would also allow signalling interactions between PGCs. We show also that the first PGCs to emigrate from the hind gut, between 9 and 9.5 d.p.c., do so directly into the area where the genital ridges will form. This suggests that an adhesive interaction between these ‘pioneer germ cells’ and the target tissue may play a role in the localisation of PGCs into the genital ridges as they aggregate.

INTRODUCTION

No relevant conflicts of interest to declare.

Risk of exposure to Borrelia burgdorferi sensu lato (s.l.) spirochetes, which include the causative agents of Lyme disease, is, in part, determined by the density of questing infected vector ticks. We sought to clarify the temporal patterns of nymphal activity, and the extent of variation in peak and cumulative densities of B. burgdorferi s.l.-infected Ixodes pacificus Cooley & Kohls nymphs, at 12 sites within the ecologically diverse Mendocino County in northwestern California. Also, we assessed the impact of various environmental characteristics (e.g., climatologic variables, habitat type, deer usage) on the aforementioned tick-related traits. The average durations of total and peak (nymphal density > 75% of absolute peak) questing activity were 31% and 82% longer, respectively, in areas with conifers present than in oak woodlands, which represented the warmest and driest habitat type examined. Peak and cumulative densities of infected nymphs varied > 400-fold between sites. Both traits were positively associated with the presence of Quercus spp. oaks or deer, and lower in redwood/tanoak versus oak and oak/Douglas fir habitats. However, a prolonged duration of nymphal activity in redwood habitats, relative to oak woodlands, resulted in a shift from peak nymphal densities occurring in oak woodlands in spring to redwood/tanoak habitats in summer. In conclusion, our data clearly show significant variability in seasonal as well as spatial risk of exposure to Lyme disease spirochetes within a small but ecologically, diverse geographic area. Hence, temporally dynamic and spatially explicit models are needed to assess the risk of exposure to tick-borne pathogens at spatial scales encompassing diverse climatologic or ecological conditions.

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