Letermovir Prophylaxis for CMV Reactivation in Allogeneic Stem Cell Recipients: A Retrospective Single Center Analysis.

BACKGROUND/AIM: Cytomegalovirus (CMV) reactivation is one of the most clinically significant complications in allogeneic stem cell recipients and a frequent cause for transplantation related mortality. Letermovir is a newly available and recently approved drug for CMV prophylaxis. In a retrospective single center analysis, we investigated the benefit of letermovir as CMV prophylaxis in allogeneic stem cell recipients. PATIENTS AND METHODS: We included 48 CMV-seropositive transplant recipients from January 2017 to August 2020 from our department. We compared the rate of CMV reactivation in patients who received letermovir as prophylaxis from day 0 after allogeneic stem cell transplantation (alloSCT) with a control group that did not receive CMV prophylaxis. The primary endpoint was CMV reactivation and was defined as an increase of CMV copies over 1250 Ul/ml in the peripheral blood; secondary endpoints were overall survival (OS) up to 180 days, engraftment and all-cause mortality. RESULTS: We included 21 patients in the control group and 27 patients in the letermovir group. Letermovir treatment led to a significantly reduced incidence of CMV reactivation after alloSCT (33.3% in the letermovir group versus 76.2% in the control group, p<0.001). The OS at day 180 was 80.9% in the control group versus 92.6% in the letermovir group (p<0.05). The median duration of letermovir prophylaxis was 192±104 days. CONCLUSION: Our results indicate that letermovir prophylaxis is associated with a significant lower risk of CMV reactivation and improved overall survival in CMV-seropositive stem cell recipients. Moreover, a prolonged use of letermovir prophylaxis might be a survival benefit.

Conditioning with fludarabine and treosulfan compared to FLAMSA-RIC in allogeneic stem cell transplantation for myeloid malignancies: a retrospective single-center analysis.

Reduced intensity conditioning (RIC) and reduced toxicity conditioning (RTC) regimens enable allogeneic hematopoietic stem cell transplantation (alloSCT) to more patients due to reduction in transplant-related mortality (TRM). The conditioning regimens with fludarabine and treosulfan (Flu/Treo) or fludarabine, amsacrine, cytarabine (FLAMSA)-RIC have shown their efficacy and tolerability in various malignancies. So far, no prospective study comparing the two regimens is available. Two studies compared the regimens retrospectively, in which both provided similar outcome. In this retrospective, single-center analysis, these two regimens were compared with regard to outcome, rate of acute and chronic graft versus host disease (GvHD), and engraftment. 113 consecutive patients with myeloid malignancies who received Flu/Treo or FLAMSA-RIC conditioning prior to alloSCT between 2007 and 2019 were included. Except for age, previous therapies, and remission status before alloSCT, patient characteristics were well balanced. The median follow-up time within this analysis was 44 months. There was no significant difference in absolute neutrophil count (ANC) or platelet engraftment between the two conditioning regimens. Overall survival (OS), the relapse-free survival (RFS), and the TRM were not significantly different between the two cohorts. The rate of GvHD did not differ between the two groups. In summary, this retrospective analysis shows that there is no major difference regarding tolerability and survival between the Flu/Treo and FLAMSA-RIC regimens. Despite several limitations due to uneven distribution concerning age and remission status, we demonstrate that Flu/Treo and FLAMSA-RIC provide similar outcomes and are feasible in older and intensively pre-treated patients.

Osteomyelitis of the First Metatarsal Head Treated With Joint-Preserving Surgery and a Synthetic Resorbable Bone Graft Substitute: A Case Report.

Managing infections of the first metatarsophalangeal joint can be demanding because many patients present with late-stage infection and partial or total amputation of the first ray or the phalanx could be necessary. We describe such a patient who was successfully treated with a calcium-based resorbable bone substitute that preserved the first metatarsophalangeal joint. A 38-year-old female presented to our department with a foot infection. Examination revealed a methicillin-susceptible Staphylococcus aureus infection of the first metatarsophalangeal joint. The histopathologic findings confirmed active osteomyelitis of the first metatarsal head. The metatarsophalangeal joint was debrided with open synovectomy, the metatarsal head was curetted, and the bone defect was filled with 2 mL of a synthetic bone graft substitute. Two years later, she reported no problems with function or pain, the joint had full range of motion, and she had no local or systemic signs of infection. The most recent radiographs revealed no damage to the first metatarsophalangeal joint. A synthetic bone graft substitute can be a good alternative for treating forefoot infections when the soft tissues are intact and the bone defect is not so large that partial or full amputation is necessary.

Structural Failure of a Modern Knee Tumor Megaendoprosthesis.

Modular knee megaendoprotheses are commonly used devices for distal femur or proximal tibia replacement in tumor surgery as well as for treatment of some periprosthetic fractures around a loose or failed total knee arthroplasty. Structural failures of the prosthesis are well-known postoperative complications and have been reported for various prosthesis types. In the majority of the cases, the polyethylene parts fail. We would like to present an unusual case of a broken femoral component of an MRH® endoprosthesis four years after implantation.

First report of an aneurysmal bone cyst presenting as subungual mass.

Painful subungual tumor masses in the toes usually emerge as glomus tumors or subungual exostoses. We present a patient with an aneurysmal bone cyst located subungually in whom the diagnosis was delayed due to inadequate diagnostic procedures, which led to marked destruction of the distal phalanx of the great toe of the right foot. After biopsy, the distal phalanx could not be preserved due to critical soft tissue involvement and the size of the process. Thus, we describe this rare entity to encourage clinicians to establish the diagnosis by biopsy of a tissue swelling of unclear origin and duration that does not resolve after a short time. Imaging examinations are useful in demonstrating periosteal involvement and extension of the lesion and can be helpful in the diagnostic algorithm. An interdisciplinary approach is a top priority to ensure optimal treatment.

Two-stage protocol and spacer implantation in the treatment of destructive septic arthritis of the hip joint.

INTRODUCTION: The ideal treatment of the destructive septic arthritis of the hip joint remains controversial. The aim of the present retrospective study was to report on our experience about the use of antibiotic-loaded cement spacers in the treatment of destructive bacterial coxitis. MATERIALS AND METHODS: 22 consecutive patients (11 male, 11 female, mean age 59.7 years) have been treated with a two-stage protocol and implantation of an antibiotic-loaded cement spacer. All patients' records have been retrospectively evaluated with regard to comorbidities/predisposing factors, infection cause, causative pathogen organism, presence of a psoas abscess, surgical time of spacer implantation, duration of spacer implantation, spacer articulation, impregnation of bone cement, systemic antibiotic therapy, surgical time of prosthesis implantation, implant type, complications, and infection control rate. RESULTS: The most common identified organism was Staphylococcus aureus (73 %). The mean duration of spacer implantation was 88 days. Spacer-specific complications were observed in 23 % of the cases and spacer non-specific ones in 50 % between stages. The mortality rate after the first stage was 18 %. Prosthesis implantation was performed in 16 cases. At a mean follow-up of 44.8 (12-120) months, the primary infection control rate (after one spacer implantation) was 87 % (13/15) and the secondary infection control rate (after two spacer implantations) 100 %. CONCLUSIONS: Two-stage treatment and spacer implantation is associated with a high rate of infection control but also with a high mortality rate between stages.

H. pylori-Induced DNA Strand Breaks Are Introduced by Nucleotide Excision Repair Endonucleases and Promote NF-κB Target Gene Expression.

The human bacterial pathogen Helicobacter pylori exhibits genotoxic properties that promote gastric carcinogenesis. H. pylori introduces DNA double strand breaks (DSBs) in epithelial cells that trigger host cell DNA repair efforts. Here, we show that H. pylori-induced DSBs are repaired via error-prone, potentially mutagenic non-homologous end-joining. A genome-wide screen for factors contributing to DSB induction revealed a critical role for the H. pylori type IV secretion system (T4SS). Inhibition of transcription, as well as NF-κB/RelA-specific RNAi, abrogates DSB formation. DSB induction further requires ß1-integrin signaling. DSBs are introduced by the nucleotide excision repair endonucleases XPF and XPG, which, together with RelA, are recruited to chromatin in a highly coordinated, T4SS-dependent manner. Interestingly, XPF/XPG-mediated DNA DSBs promote NF-κB target gene transactivation and host cell survival. In summary, H. pylori induces XPF/XPG-mediated DNA damage through activation of the T4SS/ß1-integrin signaling axis, which promotes NF-κB target gene expression and host cell survival.

Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1ß and IL-18.

The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors. Active caspase-1 processes pro-IL-1ß and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses. Little information is available on caspase-1 and inflammasome activation during infection with the gastric bacterial pathogen Helicobacter pylori. In this study, we addressed a possible role for caspase-1 and its cytokine substrates in the spontaneous and vaccine-induced control of Helicobacter infection, as well as the development of gastritis and gastric cancer precursor lesions, using a variety of experimental infection, vaccine-induced protection, and gastric disease models. We show that caspase-1 is activated and IL-1ß and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection. Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice. IL-1R(-/-) mice fail to develop protective immunity but are protected against Helicobacter-associated gastritis and gastric preneoplasia as a result of their inability to generate Helicobacter-specific Th1 and Th17 responses. In contrast, IL-18 is dispensable for vaccine-induced protective immunity but essential for preventing excessive T cell-driven immunopathology. IL-18(-/-) animals develop strongly accelerated pathology that is accompanied by unrestricted Th17 responses. In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1ß, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.