Late Infection Research Articles

Common inflammatory markers in the screening of knee arthroprosthesis infections

<p><strong>Aim<br /></strong> To evaluate the sensitivity and specificity of serum C-reactive protein (CRP) in early and late total knee arthroplasty (TKA)<br />infections.<br /><strong>Methods<br /></strong> Blood tests to determine CRP levels (cut-off 10 mg/L) were conducted before surgery, at 1st day, 7th day and 15th day after surgery and at 1, 3, 6,12, 24 and 36 months. Patients had routine follow-up visits and radiological evaluations at 14 days and at 1, 3, 6, 12, 24 and 36 months. Infections were recorded and classified according to Widmer classification. The χ2 test or Fisher (in subgroups smaller than 10 patients) exact test was used to compare categorical variables. The statistical significance was set at p < 0.05.<br /><strong>Results<br /></strong> A total of 19 infections were diagnosed during the followup. According to Widmer, five were classified as early post-operative and 14 as late chronic. All patients with early infections had suspected symptoms such as fever, swelling and pain. During the first month, 59 patients who had high CRP level but negative microbiological culture were considered as false positive representing a CRP sensitivity of 80% and a specificity of 67.6%. Fourteen patients had late chronic infection.<br /><strong>Conclusion<br /></strong> This study suggests that a synovial fluid aspiration should be performed in patients with persistent inflammation<br />symptoms with or without radiographic signs of loosening. Moreover, it recommends the use of different serum and synovial tests for periprosthetic joint infection (PJI) diagnosis.</p>

Long-Term Efficacy and Safety of Obecabtagene Autoleucel (obe-cel) in Adult Patients (pts) with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia ([R/R B-ALL]; Pooled Analysis from ALLCAR19 and FELIX Phase Ib Studies) or Other B-cell Malignancies (ALLCAR19 Extension Study)

Background: Obe-cel is an autologous CD19 chimeric antigen receptor (CAR) T cell product designed to reduce toxicity and improve persistence through a fast off-rate CD19 binding domain. The clinical activity of obe-cel has been explored in adults with R/R B-ALL in a Phase I study (ALLCAR19, NCT02935257; Roddie C et al. J Clin Oncol 2021) and a Phase Ib/II study (FELIX, NCT04404660; Roddie C et al. J Clin Oncol 2023;41[16 Suppl]:7000). Additionally, obe-cel has been tested in pts with R/R B-cell chronic lymphocytic leukemia (B-CLL) and R/R B-cell non-Hodgkin lymphoma (B-NHL) (ALLCAR19 extension; Roddie C et al. Blood 2022;140[1 Suppl]:7452-3). Pts from the ALLCAR19 and FELIX Phase Ib studies are in long-term follow up (≥22 mos), and the ALLCAR19 extension has been recruiting for 3 years. We report an analysis of long-term efficacy and safety data from the ALLCAR19 and FELIX Phase Ib studies, as well as data from the ALLCAR19 extension. Methods: ALLCAR19 is a multicenter, non-randomized, open-label Phase I study in pts aged ≥16 years with B-cell malignancies. ALLCAR19 initially recruited pts with R/R B-ALL but was then amended (extension study) to also include pts with R/R B-CLL and R/R B-NHL. FELIX is a global, single-arm Phase Ib/II study enrolling pts aged ≥18 years with R/R B-ALL.Study designs have been presented previously. Obe-cel was administered as a split dose in pts with B-ALL (target dose 410 × 10 6 CAR T cells) and pts with CLL (target dose 230 × 10 6 CAR T cells), and as a single infusion in pts with B-NHL (target dose 200 × 10 6 CAR T cells); the pt populations in the two studies were similar. Pts with B-ALL from the ALLCAR19 and FELIX Phase Ib studies are being followed long term for disease progression and survival. For this analysis, data in pts with B-ALL from the ALLCAR19 and FELIX Phase Ib studies were pooled. Data in pts with CLL or B-NHL are presented from the ALLCAR19 extension study. Results: Outcomes in pts with R/R B-ALL: Data in pts with B-ALL were pooled (20 pts from ALLCAR19 [data cut-off Jun 26, 2023] and 16 from FELIX Phase Ib [data cut-off Mar 16, 2023]). The median age of the pooled cohort was 41.5 (range 18 to 74) years and pts had received a median of 3 (range 2 to 6) prior lines of treatment. Twenty-nine of the 36 pts (81%) achieved complete remission (CR)/CR with incomplete hematologic recovery post obe-cel infusions, per investigator assessment. The event-free survival rate was 64% at 6 mos and 49% at 12 mos. With a median follow up of 43 (range 19 to 62) mos, 13/36 pts (36%) remain in remission (8 from ALLCAR19; 5 from FELIX Phase Ib). Among these 13 ongoing responders, 2 (15%) had consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ten of the 11 ongoing responders (91%) who did not receive allo-HSCT still had detectable CAR T cells at the last follow up. All ongoing remissions were measurable residual disease negative at last available assessment. The estimated 2-, 3- and 4-year overall survival rates were 44%, 39% and 39%, respectively. Outcomes in pts with R/R B-CLL/B-NHL: The extension phase of the ALLCAR19 study enrolled 35 pts with B-CLL or B-NHL, of which 26 (B-CLL n=5; B-NHL n=21) received obe-cel (data cut-off Jun 26, 2023). The median age of this combined cohort was 61 (range 39 to 79) years and pts had received a median of 3 (range 2 to 8) prior lines of treatment. At a median follow up of 24 mos, the overall response rate for this cohort was 92% (n=24), and 58% of responders (n=14) were alive without disease progression at last follow up. Late toxicity: Of the 11 long-term R/R B-ALL responders who had not received consolidation allo-HSCT, 10 have ongoing B-cell aplasia. Of the 14 ongoing responders in the R/R B-CLL/B-NHL cohort, 12 have ongoing B-cell aplasia (<20 B cells/µl). Of note, ongoing B-cell aplasia did not correlate with an increased risk of late serious infection. No other long-term toxicity ascribed to obe-cel was reported. Conclusions: The combined analysis of data from the ALLCAR19 and FELIX Phase Ib studies shows long-term efficacy and safety of obe-cel in pts with R/R B-ALL, with approximately one-third of pts still in remission without consolidative allo-HSCT after a median follow up of >3 years. Durable responses of >2 years were also seen in pts with R/R B-CLL and R/R B-NHL.B-cell aplasia was commonly found in long-term follow up of obe-cel recipients, but without a corresponding rise in serious late infections. Obe-cel can effect durable long-term remissions in B-cell malignancies.

Evidence of a conserved mammalian immunosuppression mechanism in Lutzomyia longipalpis upon infection with Leishmania.

Sand flies (Diptera: Phlebotominae) belonging to the Lutzomyia genus transmit Leishmania infantum parasites. To understand the complex interaction between the vector and the parasite, we have been investigating the sand fly immune responses during the Leishmania infection. Our previous studies showed that genes involved in the IMD, Toll, and Jak-STAT immunity pathways are regulated upon Leishmania and bacterial challenges. Nevertheless, the parasite can thrive in the vectors' gut, indicating the existence of mechanisms capable of modulating the vector defenses, as was already seen in mammalian Leishmania infections. In this study, we investigated the expression of Lutzomyia longipalpis genes involved in regulating the Toll pathway under parasitic infection. Leishmania infantum infection upregulated the expression of two L. longipalpis genes coding for the putative repressors cactus and protein tyrosine phosphatase SHP. These findings suggest that the parasite can modulate the vectors' immune response. In mammalian infections, the Leishmania surface glycoprotein GP63 is one of the inducers of host immune depression, and one of the known effectors is SHP. In L. longipalpis we found a similar effect: a genetically modified strain of Leishmania amazonensis over-expressing the metalloprotease GP63 induced a higher expression of the sand fly SHP indicating that the L. longipalpis SHP and parasite GP63 increased expressions are connected. Immuno-stained microscopy of L. longipalpis LL5 embryonic cells cultured with Leishmania strains or parasite conditioned medium showed cells internalization of parasite GP63. A similar internalization of GP63 was observed in the sand fly gut tissue after feeding on parasites, parasite exosomes, or parasite conditioned medium, indicating that GP63 can travel through cells in vitro or in vivo. When the sand fly SHP gene was silenced by RNAi and females infected by L. infantum, parasite loads decreased in the early phase of infection as expected, although no significant differences were seen in late infections of the stomodeal valve. Our findings show the possible role of a pathway repressor involved in regulating the L. longipalpis immune response during Leishmania infections inside the insect. In addition, they point out a conserved immunosuppressive effect of GP63 between mammals and sand flies in the early stage of parasite infection.

Poor Hematopoietic Reserve at the Time of CD19 CAR T-Cell Infusion Is Associated with Long Term B-Cell Aplasia

Background: On-target off-tumor toxicities of anti-CD19 CAR T-cell therapy include B-cell aplasia and hypogammaglobulinemia. Long term B-cell aplasia is hypothesized to represent functional CAR T-cell engraftment (Melenhorst, Nature 2022), while peripheral blood B-cell recovery represents the loss of functional CAR-T cells against target over time. Patients with large B-cell lymphoma (LBCL) who are clinical responders have a 50-70% chance of B-cell recovery in the first year, with the remainder experiencing longer term B-cell aplasia (Logue, Haematologica 2021). Here, we sought to identify factors associated with long term B-cell aplasia using a cohort of responding patients who received CAR T-cell therapy for LBCL. Methods:This retrospective cohort study included 57 patients with LBCL treated with CD19-targeted CAR T-cell therapy between June 2016 and August 2020 at Moffitt Cancer Center who exhibited complete or partial response at six months after CAR T-cell infusion. Patients were treated with with axicabtagene ciloleucel (axi-cel; n=50) or tisagenlecleucel (tisa-cel; n=7), either as standard-of-care therapy (n=47) or as part of a previously published clinical trial (n=10; NCT02348216, NCT03391466, NCT03153462). Peripheral blood B-cells were measured by flow cytometry using CD19 expression as part of routine clinical care at baseline and periodically after infusion. Prolonged B-cell aplasia was defined as a CD19+ B cell count comprising less than 1% of peripheral blood mononuclear cells during a minimum of two separate time points beyond 6 months of follow-up. Patients were defined as having B cell recovery if >1% B-cells were observed in peripheral blood at any time after CAR T-cell infusion. Results: At a median follow up of 33 months (95% CI: 28.7, 37.3 months), 29 (51%) patients had persistent B-cell aplasia and 28 (49%) had recovery of peripheral B-cell counts. Median B-cell count at 12 months in the recovery group was 84/µL (IQR 2.5-197) compared to 0/µL (IQR 0-1) in the aplasia group. Patients with long-term B-cell aplasia had lower CD4 T-cell counts prior to CAR T-cell infusion [median 200/µL (IQR 136-278) vs. 330/µL (IQR 224-451); P= 0.008] and over time compared to patients with B-cell recovery (Fig. A). Patients with long-term B cell aplasia also had lower pre-infusion absolute neutrophil counts (2.3K/µL (IQR 1.4-4.15) vs. 3.5K/µL (IQR 2.8-4.2); P<0.001) and higher baseline CAR-HEMATOTOX scores [2 (IQR 1-3.25) vs 1 (IQR 0-1)], consistent with poor baseline hematopoietic reserve (Rejeski, Blood 2021). While disease-related mortality did not significantly differ between groups, non-relapse mortality was markedly higher in patients with long-term B-cell aplasia due to infection: all 8 patient deaths in the aplasia group were due to infections occurring beyond day 30 post-infusion, with 6 of the 8 deaths due to COVID-19. However, no patients in the B-cell recovery group died of late infection (Fig. B). Conclusions: Long term B-cell aplasia is hypothesized to represent ongoing CAR T-cell activity against normal B-cells. However, our results demonstrate that B-cell aplasia is associated with low baseline hematopoietic reserve and subsequent poor immune reconstitution of multiple lineages including B-cells, T-cells, and myeloid cells. Further studies are warranted to assess whether poor immune reconstitution and B-cell aplasia are related to long term CAR T-cell activity or other processes. These patients are at higher risk for non-relapse mortality from infection, and mitigation strategies are needed.

An insight into outbreak of atypical mycobacterial infection following percutaneous nephrolithotomy - Role of cleaning and sterilization techniques inspected

Background: Atypical wound infections following minimal access surgery continue to affect smooth recovery. Percutaneous nephrolithotomy (PCNL) for renal stones involves various small-sized nephroscopes and accessories. Improper cleaning and disinfection of which may result in bacterial biofilms formation and infections. Aims and Objectives: We inspected an outbreak of atypical wound infection after PCNL to find the responsible factor. Materials and Methods: This retrospective observational study had three groups based on cleaning and sterilization methods. In group A, manual cleaning of instruments was done followed by high-level disinfection using glutaraldehyde 2% solution with 20 min submersion. In group B, manual cleaning was supplemented with multienzyme cleaning with 10 min submersion but disinfection method was same as in group A. In group C, manual and enzyme cleaning was combined with ethylene oxide (ETO) sterilization. The outcome was assessed as wound infection occurrence at 1-month follow-up. Results: The study had 81 participants with 61 male and 20 females. The mean age was 36±16 years. Group A, B, and C had 32, 24, and 25 participants, respectively. Pre-operative parameters were comparable among the groups. Late wound infection (at 1-month follow-up) occurred in 11 cases from group A, but none from others (P=0.004). Culture-revealed atypical mycobacterial growth in four cases, while Staphylococcus in another. Rests were sterile. Six patients were relieved after clarithromycin course for 1–5 months. Three patients needed scar excision. Conclusion: Manual cleaning with high-level disinfection is not adequate against atypical mycobacterial infections. A combination of enzymatic cleaning and high-level disinfection with glutaraldehyde or ETO sterilization effectively minimizes these infections.

DRG2 in macrophages is crucial for initial inflammatory response and protection against Listeria monocytogenes infection

Innate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection. Both whole-body DRG2 knockout (KO) mice and macrophage-specific DRG2 KO mice had low levels of IL-6 during early infection and increased susceptibility to L. monocytogenes infection. Following an initial impaired inflammatory response of macrophages upon i.p. L. monocytogenes infection, DRG2−/− mice showed delayed recruitment of neutrophils and monocytes into the peritoneal cavity, which led to elevated bacterial burden, inflammatory cytokine production at a late infection time point, and liver micro-abscesses. DRG2 deficiency decreased the transcriptional activity of NF-κB and impaired the inflammatory response of both bone marrow-derived and peritoneal macrophages upon L. monocytogenes stimulation. Our findings reveal that DRG2 in macrophages is critical for the initial inflammatory response and protection against L. monocytogenes infection.

Nodule-specific Cu+ -chaperone NCC1 is required for symbiotic nitrogen fixation in Medicago truncatula root nodules.

Cu+ -chaperones are a diverse group of proteins that allocate Cu+ ions to specific copper proteins, creating different copper pools targeted to specific physiological processes. Symbiotic nitrogen fixation carried out in legume root nodules indirectly requires relatively large amounts of copper, for example for energy delivery via respiration, for which targeted copper deliver systems would be required. MtNCC1 is a nodule-specific Cu+ -chaperone encoded in the Medicago truncatula genome, with a N-terminus Atx1-like domain that can bind Cu+ with picomolar affinities. MtNCC1 is able to interact with nodule-specific Cu+ -importer MtCOPT1. MtNCC1 is expressed primarily from the late infection zone to the early fixation zone and is located in the cytosol, associated with plasma and symbiosome membranes, and within nuclei. Consistent with its key role in nitrogen fixation, ncc1 mutants have a severe reduction in nitrogenase activity and a 50% reduction in copper-dependent cytochrome c oxidase activity. A subset of the copper proteome is also affected in the ncc1 mutant nodules. Many of these proteins can be pulled down when using a Cu+ -loaded N-terminal MtNCC1 moiety as a bait, indicating a role in nodule copper homeostasis and in copper-dependent physiological processes. Overall, these data suggest a pleiotropic role of MtNCC1 in copper delivery for symbiotic nitrogen fixation.

Dynamic hip screw versus proximal femoral nail in the treatment of intertrochanteric fracture of femur

Background: As the elderly population grows, the number of hip fractures continues to increase. This study aims to compare the clinical outcomes of dyanamic hip screw and proximal femoral nail in the fixation of intertrochanteric fracture of femur. Methods: After obtaining approval of the ethics committee, a prospective study was conducted in the department of orthopedics, SKR Hospital, Pathankot from January 2021 till December 2022. Informed consent was taken from patients who fulfilled the inclusion/exclusion criteria and relevant clinical information was collected, including intra and post-operative details. Results: During the study period, 65 patients with intertrochanteric fracture were included in the study, of which 33 were treated with PFN and 32 with DHS. It was observed that 91% of the patients who underwent PFN had blood loss less than 100 ml, while 72% of the patients who had DHS had blood loss between 100-300 ml. Mobilization started on the first postoperative day in 67% of PFN patients while as compared to 13% of DHS patients (p value <0.01). Among late complications, there was one case of implant failure among PFN cases, while there were two cases of non-union, two cases of implant failure and one case of late infection among DHS group of patients. It was observed that 91% of PFN group patients had excellent outcomes, while outcome was excellent in 66% of DHS group patients. Conclusions: Our study showed that PFN is a superior method of osteosynthesis as compared to DHS in the treatment of intertrochanteric fractures.

Management of Human Bites in a Rural Kenyan Setting: A Plastic Surgeon's 8-Year Experience.

The treatment of human bites is a common issue facing healthcare practitioners in the developing countries of Sub-Saharan Africa where it has been noted as a growing public health concern. Generally, the desired outcomes from surgical management are healing, function, and aesthetics. We share our 8-year experience at Kapsowar Hospital in Kenya with the presentation, management, and outcome of human bites. We are uniquely situated to do so given the prevalence of human biting in our community and the full-time presence of a plastic surgeon at our institution. To the best of our knowledge, this study is the first to present human bite surgical management by a plastic surgeon certified by the American Board of Surgery working full-time on the African continent. A retrospective chart review was conducted on all patients who presented to the operating theater at Kapsowar Hospital with a human bite between 2013-2021. After identification of eligible patients, charts were reviewed assessing parameters including age, gender, timing from injury to presentation at hospital, localization of bite, severity of facial wounds using Lackmann's classification, surgical procedure(s), postoperative complications, surgical revisions, antibiotics administered, and circumstance of incident. Data were analyzed using SPSS 29.0.0.0. Forty-four patients were identified. Seventeen (38.6%) were female and 27 (61.4%) were male. Thirty-one patients had facial bites and 13 patients had bites to other parts of the body. Of facial bites, 70.3% resulted in amputation of the affected part while 29.7% were lacerations. Using Lackmann's classification for facial bite severity, IIIA bites (complete avulsion) were most common for both males (9) and females (7). Females comprised 68.4% of total lip bite victims. Bites to the extremity were associated with late presentation and infection. We report a salvage rate of 85.7% for infected digits. Compared with most other studies on human bites, our patient population presents with a higher rate of avulsive lip injuries, most commonly among women. Our postoperative infection rate is lower than many others reported in the literature. Satisfactory cosmetic outcome with low risk of infection can be achieved by following well-established principles of wound healing and tension-free closure.

Long-Term Neurodevelopmental Impairment among Very Preterm Infants with Sepsis, Meningitis, and Intraventricular Hemorrhage

Introduction: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. Methods: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. Results: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. Conclusion: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.

The first genomic characterization of a stable, hemin-dependent small colony variant strain of Staphylococcus epidermidis isolated from a prosthetic-joint infection

Phenotype switching from a wild type (WT) to a slow-growing subpopulation, referred to as small colony variants (SCVs), supports an infectious lifestyle of Staphylococcus epidermidis, the leading cause of medical device-related infections. Specific mechanisms underlying formation of SCVs and involved in the shaping of their pathogenic potential are of particular interest for stable strains as they have been only rarely cultured from clinical specimens. As the SCV phenotype stability implies the existence of genetic changes, the whole genome sequence of a stable, hemin-dependent S. epidermidis SCV strain (named 49SCV) involved in a late prosthetic joint infection was analyzed. The strain was isolated in a monoculture without a corresponding WT clone, therefore, its genome was compared against five reference S. epidermidis strains (ATCC12228, ATCC14990, NBRC113846, O47, and RP62A), both at the level of the genome structure and coding sequences. According to the Multilocus Sequence Typing analysis, the 49SCV strain represented the sequence type 2 (ST2) regarded as the most prominent infection-causing lineage with a worldwide dissemination. Genomic features unique to 49SCV included the absence of the Staphylococcal Cassette Chromosome (SCC), ~12 kb deletion with the loss of genes involved in the arginine deiminase pathway, and frameshift-generating mutations within the poly(A) and poly(T) homopolymeric tracts. Indels were identified in loci associated with adherence, metabolism, stress response, virulence, and cell wall synthesis. Of note, deletion in the poly(A) of the hemA gene has been considered a possible trigger factor for the phenotype transition and hemin auxotrophy in the strain. To our knowledge, the study represents the first genomic characterization of a clinical, stable and hemin-dependent S. epidermidis SCV strain. We propose that previously unreported indels in the homopolymeric tracts can constitute a background of the SCV phenotype due to a resulting truncation of the corresponding proteins and their possible biological dysfunction. Streamline of genetic content evidenced by the loss of the SCC and a large genomic deletion can represent a possible strategy associated both with the SCV phenotype and its adaptation to chronicity.

Structured approach for infected prosthesis

Endoprosthesis infections represent amajor challenge for doctors and patients. Due to the increase in endoprosthesis implantation because of the increasing life expectancy, an increase in endoprosthesis infections is to be expected. In addition to infection prophylaxis, methods of infection control become highly relevant, especially in the group of geriatric and multimorbid patients. The aim is to reduce the high 1‑year mortality from prosthesis infections through astructured algorithm. Prosthesis infections can basically be divided into early and late infections. According to the criteria of the International Consensus Meeting, alate infection is defined as the occurrence more than 30days after implantation. With respect to the planned approach, the (p)TNM classification offers an orientation. In the early postoperative interval the clinical appearance is crucial as in this phase neither laboratory parameters nor an analysis of synovial fluid show ahigh sensitivity. It is fundamental that, apart from patients with sepsis, environment diagnostics should be initiated. If alate infection is suspected, in addition to radiological diagnostics (X-ray, skeletal scintigraphy and if necessary, computed tomography, CT), laboratory (C-reactive protein, CRP, leukocytes, blood sedimentation, and if necessary, interleukin‑6, procalcitonin) and microbiological diagnostics (arthrocentesis with synovial analysis and microbiology) are indicated; however, in addition to the arthrocentesis result, the clinical appearance is crucial in cases where an exclusion cannot be confirmed by laboratory parameters. If an infection is confirmed, the treatment depends on the spectrum of pathogens, the soft tissue situation and the comorbidities, including amultistage procedure with temporary explantation and, if necessary, implantation of an antibiotic-containing spacer is necessary. Aprosthesis preservation using the debridement, antibiotics and implant retention (DAIR) regimen is only appropriate in an acute infection situation. Basically, radical surgical debridement should be carried out to reduce the pathogen load and treatment of apossible biofilm formation for both early and late infections. The subsequent antibiotic treatment (short or long interval) should be coordinated with the infectious disease specialists. Astructured approach for prosthesis infections oriented to an evidence-based algorithm provides asufficient possibility of healing. An interdisciplinary approach involving cooperation between orthopedic and infectious disease specialists has proven to be beneficial. Surgical treatment with the aim of reducing the bacterial load by removing the biofilm with subsequent antibiotic treatment is of intrinsic importance.

Daily turnover of active giant virus infection during algal blooms revealed by single-cell transcriptomics.

Giant viruses infect many unicellular eukaryotes, including algae that form massive oceanic blooms. Despite the major impact of viruses on the marine ecosystem, the ability to quantify and assess active viral infection in nature remains a major challenge. We applied single-cell RNA sequencing, to profile virus and host transcriptomes of 12,000 single algal cells from a coccolithophore bloom. Viral infection was detected already at early exponential bloom phase, negatively correlating with the bloom intensity. A consistent percent of infected coccolithophores displayed the early phase of viral replication for several consecutive days, indicating a daily turnover and continuous virocell-associated metabolite production, potentially affecting the surrounding microbiome. Linking single-cell infection state to host physiology revealed that infected cells remained calcified even in the late infection stage. These findings stress the importance of studying host-virus dynamics in natural populations, at single-cell resolution, to better understand virus life cycle and its impact on microbial food webs.

Septic Arthritis of Neonates: A Rare Case Report

Neonatal septic arthritis is a rare condition which may present as an orthopedic emergency. The sequalae may be devastating in untreated cases. The presentation of neonatal septic arthritis could lead to multitude of differential diagnosis which consequentially delays the final diagnosis. It is very crucial to make an early diagnosis in such cases and commence prompt or timely appropriate management to prevent serious complications. Worldwide incidence in the neonatal age group is 0.3 per 1000 live births, although higher incidence of 0.6 per 1000 live birth has been reported in India, [1,2]. Older children are affected more than the younger age group and the hip joint is most commonly affected because of its unique anatomy and blood supply. The Pathogenic bacteria most commonly found to be responsible for septic arthritis are staphylococcus aureus, haemophilus influenza and streptococcus agalactiae (GBS). We are reporting a rare case of septic arthritis in the shoulder joint to a neonate caused by GBS bacteria, presenting as a late onset infection.

Early detection of Phytophthora infestans in potato plants using hyperspectral imaging, local comparison and a convolutional neural network

An important primary inoculum source of Phytophthora infestans are latent infected seed potatoes. To remove those inoculum sources, it is necessary to detect these plants before symptom expression. Often, when a human can detect it by eye, sporulation has occurred and secondary spread might have commenced. Moreover, it is not feasible to check all potato plants by manual labour. It is possible to detect a P. infestans infection early, using hyperspectral imaging, however, models trained on the spectral information only, do not generalize, because the spectrum is very much dependent on the local conditions like soil humidity. A method is developed to detect P. infestans early by comparing spectra from infected plants with the spectra of healthy plants that have grown under similar conditions, i.e., in the same plant row, and creating an image that quantifies deviations. On those images in turn a convolutional neural network is trained, which is able to detect infections on plants grown in another field or a year later in a similar manner but under different conditions. The method has been tested in the field in a dry year with little potato late blight infection. In this experiment it has not been possible to detect the infection using hyperspectral imaging.

Investigating infectious outcomes in adult patients undergoing solid organ transplantation: A retrospective single-center experience, Paris, France.

This study described the demographic characteristics, clinical presentation, treatment, and outcomes of solid organ transplant recipients who were admitted to our center for infection. It also determined factors associated with a poor outcome, and compares early and late period infections. In this retrospective observational study, conducted at a tertiary care center in France between October 2017 and March 2019, infectious outcomes of patients with solid organ transplant where studied. A total of 104 patients were included with 158 hospitalizations for infection. Among these 104 patients, 71 (68%) were men. The median age was 59 years old. The most common symptoms on admission were fever (66%) and chills (31%). Lower respiratory tract infections were the most common diagnosis (71/158 hospitalizations). Urinary tract infections were frequently seen in kidney transplant recipients (25/60 hospitalizations). One or more infectious agents were isolated for 113 hospitalizations (72%): 70 bacteria, 36 viruses and 10 fungi, with predominance of gram-negative bacilli (53 cases) of which 13 were multidrug-resistant. The most frequently used antibiotics were third generation cephalosporins (40 cases), followed by piperacillin-tazobactam (26 cases). We note that 25 infections (16%) occurred during the first 6 months (early post-transplant period). Patients admitted during the early post-transplant period were more often on immunosuppressive treatment with prednisone (25/25 VS 106/133) (p = 0.01), mycophenolic acid (22/25 VS 86/133) (p = 0.03), presented for an urinary tract infection (10/25 VS 25/133) (p = 0.04) or a bacterial infection (17/25 VS 53/133) (p = 0.01). Patients with later infection had more comorbidities (57/83 VS 9/21) (p = 0.03), cancer (19/83 VS 0/21) (p = 0.04) or were on treatment with everolimus (46/133 VS 0/25) (p = 0.001). During 31 hospitalizations (20%), patients presented with a serious infection requiring intensive care (n = 26; 16%) or leading to death (n = 7; 4%). Bacteremia, pulmonary and cardiac complications were the main risk factors associated with poor outcome. Infections pose a significant challenge in the care of solid organ transplant patients, particularly those with comorbidities and intensive immunosuppression. This underscores the crucial importance of continuous surveillance and epidemiologic monitoring within this patient population.

Signature of cardiac alterations in early and late chronic infections with Trypanosoma cruzi in mice.

Chagas disease by Trypanosoma cruzi (T. cruzi) infection is a leading cause of myocarditis worldwide. Chagas cardiomyopathy is presented with a wide variety of conduction abnormalities including arrhythmias, first- and second-degree atrioventricular blockade, left ventricular systolic dysfunction and some cases heart failure leading to the death. Currently, there are no effective treatments available against advanced Chagas disease. With the advance in the development of novel therapies, it is important to utilize an animal model that can effectively replicate the diverse stages of Chagas disease, including chronic asymptomatic and symptomatic infection, that are akin to those observed in humans. Therefore, to characterize the cardiac alterations during the evolution of the infection, we evaluated the progression of cardiomyopathy caused by T. cruzi H1 infection in both BALB/c and ICR mouse models by performing electrocardiogram (ECG) studies in unanesthetized mice every month until 210 days post-infection (dpi). In the late chronic phase of infection, we also performed echocardiogram (ECHO) studies to further assess cardiac function. In conclusion, we demonstrated that ICR mice were more susceptible to cardiac alterations compared to BALB/c mice and both mouse strains are suitable experimental models to study chronic T. cruzi infection and novel treatments.

Periprosthetic infection after total hip arthroplasty in polytrauma victims

Infectious complications during endoprosthesis of large joints are one of the urgent medical and socio-economic problems of modern orthopedics and traumatology. The purpose of the study was to improve the results of treatment of periprosthetic infection in patients after total hip arthroplasty as a result of polytrauma by determining the features of the course and diagnosing it in this category of patients. To carry out the study, a retrospective analysis of 87 cases of periprosthetic infection was conducted in patients undergoing inpatient treatment at the Kyiv City Clinical Hospital of Emergency Medical Care for the period 2012–2020 and divided into observation and control groups. Іn the first group, acute postoperative periprosthetic infection (up to 4 weeks) was detected in 33 victims, which was 71.7% of the group. In the second group, this type of periprosthetic infection was detected in 23 victims, which was 56.1% of the group. Late chronic infection (from 4 weeks to 1 year) among the victims of the first group was found in 10 patients, which was 21.7% of the group. In the second group, there were 11 patients with late periprosthetic infection, which was 24.4% of the group. All patients participating in the study were divided into observation and control groups. Periprosthetic infection after total hip arthroplasty in polytrauma victims develops more often in the early stages, up to 4 weeks. In addition to gram-positive cocci, the causes of periprosthetic infection are often gram-negative enterobacteria, which indicates the prevalence of the endogenous route of infection in this category of patients. Among the etiological factors of periprosthetic infection after total hip arthroplasty in polytrauma victims, Acinetobacter spp. is quite often found, which is a consequence of long-term use of invasive methods of treatment and monitoring performed on the patient during the treatment of traumatic injuries. Keywords: large joints, arthroplasty, microorganisms, complications, multiple trauma.

A comparative transcriptome analysis of how shrimp endure and adapt to long-term symbiosis with Enterocytozoon hepatopenaei infection

Enterocytozoon hepatopenaei (EHP) is a prevalent microsporidian pathogen responsible for hepatopancreatic microsporidiosis (HPM) in Litopenaeus vannamei. This infection not only leads to slowed growth in shrimp abut aslo inflicts substantial economic losses in the global aquaculture industry. However, the molecular mechanisms by which EHP influences the host during various infection stages remain unclear. This study employed comparative transcriptomics to examine the effects of EHP infection on Litopenaeus vannamei between early and late stage of infection groups. Utilizing transcriptomic approaches, we identified differentially expressed genes (DEGs) with notable biological significance through the COG, GO, KEGG, GSEA, and Mufzz time-series methodologies. The results reveal that EHP infection considerably influences host gene expression, with marked differences between early and late infection across distinct timeframes. Key processes such as detoxification, cell apoptosis, and lipid metabolism are pivotal during host-parasite interactions. Hexokinase and phosphatidic acid phosphatase emerge as key factors enabling invasion and sustained effects. Cytochrome P450 and glucose-6-phosphate dehydrogenase could facilitate infection progression. EHP significantly impacts growth, especially through ecdysteroids and 17β-estradiol dehydrogenase. By delineating stage-specific effects, we gain insights into interaction between EHP and Litopenaeus vannamei, showing how intracellular pathogens reprogram host defenses into mechanisms enabling long-term persistence. This study provides a deeper understanding of host-pathogen dynamics, emphasizing the interplay between detoxification, metabolism, immunity, apoptosis and growth regulation over the course of long-term symbiosis.

Ten Year Outcomes of Contemporary Total Hip Arthroplasty in Adolescent and Young Adult Patients are Favorable

BackgroundThe purpose of this study was to assess 10-year patient-reported outcome measures, complications, polyethylene wear-rates, and implant survivorships in patients ≤30 years of age treated with contemporary total hip arthroplasty (THA). MethodsWe retrospectively assessed 121 patients (144 hips) who underwent THA at age ≤30 years (mean 23 [range, 11 to 30]) at an average follow-up duration of 10.7 years (range, 8 to 17). Highly-crosslinked polyethylene acetabular liners were used in all cases. Femoral heads were ceramic (74%) or cobalt-chrome (26%). There were 52 hips (36%) that had previous surgery and 31 hips (22%) were in patients who had associated major systemic comorbidities. We analyzed the modified Harris Hip scores, University of California Los Angeles Activity Scores, major complications, polyethylene wear-rates, and implant survivorships. ResultsAt final follow-up, the average modified Harris Hip scores improved from 47 (±15.1) to 81 (±19.5) with an average 34-point improvement. The University of California Los Angeles scores improved from 4.0 (±2.3) to 6.0 (±2.4). The major complication rate was 5.6%. There were 6 hips (4.2%) that were revised. Indications for revision included instability (3, 2.1%), late infection (1, 0.7%), liner dissociation (1, 0.7%), and acetabular loosening (1, 0.7%). Mean linear (0.0438 mm/y) and volumetric (29.07 mm3/y) wear rates were low. No periprosthetic osteolysis was detected in any hip. Survivorship free from revision for any reason was 97.2, 95.8, and 95.8% at 5, 10, and 15 years. ConclusionsContemporary THA in patients ≤30 years of age is associated with marked clinical improvements at 10-year follow-up and encouraging survivorship estimates at 15 years.