Long-Term Immunological Alertness and Response to COVID-19 Vaccination-Conditions for Prevention in Early Palliative Oncological Care Patients.

Aside from the general population, the COVID-19 pandemic has also affected a group of patients in palliative oncology care. In this study, long-term immune responses against SARS-CoV-2 after vaccination were monitored in a cohort of patients in palliative oncology care. This non-randomized, prospective, and open-label pilot study recruited patients from the Palliative Oncology Program and included 147 patients, of which 80 were females (54.4%) and 67 males (45.6%). The overall evaluation included current health status, SARS-CoV-2 anti-S IgG titer, and neutralizing antibodies using the SARS-CoV-2 virus neutralization test (VNT). Anti-S IgG antibody analysis revealed high (H) antibody levels in 35.7% (n = 10) and very high (VH) levels in 39.3% (n = 11) of patients after the second vaccination dose. Similarly, after the third dose, H was found in 29.6% (n = 32) and VH in 55.5% (n = 60) of patients. High and very high anti-S IgG antibody levels were consistent with high VNT titers (>2560) and H antibody levels in 17.1% (n = 12) or VH in 82.9% (n = 58) of patients. Patients with two or more doses showed H and VH antibody levels at a median of 451 and 342 days after vaccination, respectively. In this clinical trial, patients showed high and very high levels of anti-S IgG antibodies over a longer period of time. These patients did not show reduced immunological responses to the COVID-19 vaccine challenge. We can assume that prevention through vaccination can reduce the risk of complications or death from COVID-19 in patients in early palliative oncology care.

Nasal Immunization Using Chitosan Nanoparticles with Glycoprotein B of Murine Cytomegalovirus.

The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.

The sensitivity and specificity of Abbott Panbio™ COVID 19 Ag Rapid test in the context of four SARS-CoV-2 variants.

Rapid antigen tests for the detection of SARS-CoV-2 are commonly used for the diagnosis of Covid-19. Previously published data showed a wide range of sensitivity and specificity of RATs, but these studies were performed on relatively small numbers of samples and using only limited numbers of virus variants. The aim of the study was to evaluate the main parameters of a commonly used RAT for 4 different virus variants in comparison with PCR. Material and methods: A set of 2874 samples obtained from Covid-19 patients were examined both by PCR and RAT. Two commercial PCR kits (Generi Biotech, Diana Biotechnologies) and one RAT - Abbott Panbio™ COVID 19 Ag Rapid - were compared for their sensitivity and specificity in samples positive for one of the four different SARS-CoV-2 variants - B.1.258 (n = 496), Alpha (n = 645), Delta/Delta+ (n = 687), and Omicron (n = 1046). Results: The sensitivity of Panbio™ COVID19 Ag Rapid test varied from 80.0 % in Omicron to 88.92 % in Alpha variants. The specificities of the RAT for all variants reached above 93 %. Statistically significant differences were found between the results from RAT assay in select virus variants. In addition, significantly higher sensitivity (p < 0.05) was detected in samples with higher viral loads than in those with lower. Conclusion: Despite the different sensitivity and specificity of Panbio™ COVID19 Ag Rapid test (Abbott ®) for different SARS-CoV-2 variants, this test sensitivity was proven to be always above the 80 % suggested by WHO, which makes it suitable for common use, regardless of the virus variability.

Multicentric evaluation of sensitivity of eight commercial anti-SARS-CoV-2 antibody assays and their correlation to virus neutralization titers in seropositive subjects.

Diagnosis of SARS-CoV-2 virus is mainly based on direct detection. Determination of specific antibodies has been used mostly for epidemiological reasons. However, select immunoassays showed good correlation to plaque reduction virus neutralization test (PRNT) in smaller patient cohorts, which suggests their potential as predictors of virus neutralization titer. A total of 3,699 samples from Covid-19 patients were included in the multicentric study performed in the Czech Republic. Anti-SARS-CoV-2 antibody levels were evaluated by 8 commercial antibody assays. Simultaneously, PRNT evaluations were performed with the SARS-CoV-2 B.1.258 variant. All immunoassays showed an overall high true positive diagnostic value ranging from 79.17 to 98.04%. Several commercial EIA methods showed highly positive correlation between the assay results and PRNT levels, e.g., Liaison CoV-2 TrimericS IgG DiaSorin (Spearman r = 0.8833; Architect SASRS-CoV-2 IgG Abbott (r = 0.7298); NovaLisa SARS-CoV-2 IgG NovaTec (r = 0.7103) and Anti-SARS-CoV-2 ELISA IgG Euroimmun (r = 0.7094). While this correlation was less positive for other assays, those, conversely, presented higher true positive values. For most immunoassays, the positive percent agreement of the results was ≥ 95% in sera exhibiting PRNT levels of 1:80 and higher. The assays tested have shown variable correlation to PRNT. Those possessing high positive predictive values serve well as qualitative tests, while others can be utilised as quantitative tests highly predictive of neutralization antibody levels.

Comparison of adverse reactions of spiramycin versus pyrimethamine/sulfadiazine treatment of toxoplasmosis in pregnancy: is spiramycin really the drug of choice for unproven infection of the fetus?

BACKGROUND: Therapeutic regimens for the treatment of toxoplasmosis are not standardized. Treatment strategy mainly at the end of the second and the beginning of the third trimester, especially in cases of negative prenatal diagnosis, is the least uniform. In some situations, the choice of treatment may be ambiguous, and adverse drug reactions of the therapy should be taken into consideration. METHODS: Adverse drug reactions of anti-toxoplasma therapy with spiramycin (n = 77) versus pyrimethamine/sulfadiazine (n = 35) were compared in 112 pregnant women. RESULTS: Up to 36.6% of women reported adverse reactions to the treatment overall (n = 41). Out of those 38.9% (n = 30) were treated with spiramycin and 31.4% (n = 11) with pyrimethamine/sulfadiazine. Toxic allergic reactions were the only indication for discontinuation of treatment in 8.9% of patients (n = 10), where 9.1% (n = 7) were reported in spiramycin and 8.6% (n = 3) in pyrimethamine/sulfadiazine cohort. Neurotoxic complications (acral paraesthesia) were significantly more frequent during the therapy with spiramycine in 19.5% (n = 15) compared to no cases in pyrimethamine/sulfadiazine group (p = .003). Other adverse drug reactions, such as gastrointestinal discomfort, nephrotoxicity, vaginal discomfort were reported, but the differences between the cohorts were not significant. CONCLUSIONS: The superiority of one of the therapeutic regimens was not statistically demonstrated, since the differences in overall toxicity or incidence of toxic allergic reactions between the cohorts were not confirmed (p = .53 and p = 1.00, respectively). However, although the isolated neurotoxicity of spiramycin was the only significant adverse reaction demonstrated in this study, pyrimethamine/sulfadiazine therapy should be preferred, because it is known to be more effective and with limited adverse reactions.

A Rare Case of Osteomyelitis of an Ankle Caused by Mycobacterium chelonae.

Mycobacterium chelonae, a rapidly growing nontuberculous mycobacterium, is usually described as a causative agent of soft tissue infections (postsurgical, posttraumatic, posttransplantation, postinjection, catheter infection, etc.), but only rarely as a cause of osteomyelitis. The authors describe a case report of a 72-year-old man with osteomyelitis of the talus. Initially, the infection was assessed as a soft tissue infection, without any osteolytic changes on the X-ray. After cultivation with subsequent targeted molecular typing of the rpoB gene, M. chelonae was identified from the affected tissue. The bone involvement was subsequently detected on MRI and confirmed histologically with findings of the granulomatous tissue and acid-fast bacilli. The patient was initially treated intravenously with a combination of tigecycline, amikacin, and moxifloxacin for 4 weeks, after which the oral combination of doxycycline and moxifloxacin continued. Identification of the infecting pathogen using molecular typing thus helped to establish the correct diagnosis and represents a rarely described case of osteomyelitis caused by M. chelonae.

Intra-amniotic inflammation and birth weight in pregnancies with preterm labor with intact membranes: A retrospective cohort study.

Objective: To assess the association between newborn birth weight and the presence of intra-amniotic infection, presence of sterile intra-amniotic inflammation, and absence of intra-amniotic inflammation in pregnancies with preterm labor with intact membranes. Methods: A total of 69 pregnancies with preterm labor with intact membranes between gestational ages 22 + 0 and 34 + 6 weeks who delivered within seven days of admission were included in this retrospective cohort study. Transabdominal amniocentesis to determine the presence of microorganisms and/or their nucleic acids in amniotic fluid (through culturing and molecular biology methods) and intra-amniotic inflammation (according to amniotic fluid interleukin-6 concentrations) were performed as part of standard clinical management. The participants were further divided into three subgroups: intra-amniotic infection (presence of microorganisms and/or nucleic acids along with intra-amniotic inflammation), sterile intra-amniotic inflammation (intra-amniotic inflammation alone), and without intra-amniotic inflammation. Birth weights of newborns were expressed as percentiles derived from the INTERGROWTH-21st standards for (i) estimated fetal weight and (ii) newborn birth weight. Results: No difference in birth weights, expressed as percentiles derived from the standard for estimated fetal weight, was found among the women with intra-amniotic infection, with sterile intra-amniotic inflammation, and without intra-amniotic inflammation (with infection, median 29; with sterile inflammation, median 54; without inflammation, median 53; p = 0.06). Differences among the subgroups were identified in the birth weight rates, expressed as percentiles derived from the standard for estimated fetal weight, which were less than the 10th percentile (with infection: 20%, with inflammation: 13%, without inflammation: 0%; p = 0.04) and 25th percentile (with infection: 47%, with inflammation: 31%, without inflammation: 9%; p = 0.01). No differences among the subgroups were observed when percentiles of birth weight were derived from the birth weight standard. Conclusions: The presence of intra-amniotic inflammatory complications in pregnancies with preterm labor with intact membranes prior to the gestational age of 35 weeks was associated with a higher rate of newborns with birth weight less than the 10th and 25th percentile, when percentiles of birth weight were derived from the standard for estimated fetal weight.

Dual Infection of an Open Fracture Caused by Mycobacterium setense and Clostridium celerecrescens.

Infections caused by Mycobacterium setense or Clostridium celerecrescens are extremely rare. In this report, for the first time a dual infection with these two pathogens is described. An 18-year-old female suffered multiple injuries, including an open comminuted fracture of the right humeral diaphysis after falling from a fifth-floor balcony in January 2019. Five months after the accident, a fistula appeared in the scar, reaching the bone tissue. M. setense and C. celerecrescens were cultured from sinus swabs and subsequently from perioperative samples. The patient was initially treated with a combination of intravenous antibiotics (ATBs): imipenem, amikacin, and ciprofloxacin. One month after the fracture fixation with a titanium nail, C. celerecrescens was again detected; therefore, metronidazole was added to the therapy. A triple combination of oral (PO) ATBs (trimethoprim-sulfamethoxazole, moxifloxacin, and metronidazole) followed, 8 weeks after the initial intravenous therapy. C. celerecrescens was cultured again two times, most recently in November 2019, when surgical debridement was supplemented by the topical administration of cancellous bone impregnated with vancomycin. Signs of bone healing were found at follow-ups and ATB treatment was finished in March 2020 after a total of 9 months of therapy. To this day, there have been no signs of reinfection. This case thus illustrates the need for a combination of systemic and individualized local therapy in the treatment of complicated cases of dual infections with rare pathogens.

Mycobacterioses Induced by Mycobacterium abscessus: Case Studies Indicating the Importance of Molecular Analysis for the Identification of Antibiotic Resistance.

Mycobacterioses are less frequently occurring but serious diseases. In recent years, at a global level, the incidence of mycobacterioses induced by the rapidly growing species Mycobacterium abscessus (M. a.), which is considered to be the most resistant to antibiotics and most difficult to treat, has been on the rise. Correct identification to the level of the subspecies (M. a. abscessus, M. a. massiliense, and M. a. bolletii) and determination of its sensitivity to macrolides, which are the basis of combination therapy, are of principal importance for the management of the disease. We describe five cases of mycobacterioses caused by M. a., where the sequencing of select genes was performed to identify the individual subspecies and antibiotic resistance. The analysis of the rpoB gene showed two isolates each of M. a. abscessus and M. a. massiliense and one isolate of M. a. bolletii. The complete (full length) erm(41) gene responsible for the development of inducible resistance to macrolides was demonstrated in both M. a. abscessus and M. a. bolletii isolates. A partially deleted and non-functional erm(41) gene was demonstrated in M. a. massiliense isolates. The subsequent sequencing of the full length erm(41) gene products showed, however, the mutation (T28→C) in both isolates of M. a. abscessus, causing a loss of the function and preserved sensitivity to macrolides. The antibiotic sensitivity testing confirmed that both the isolates of M. a. abscessus and M. a. massiliense were sensitive to clarithromycin even after prolonged 14-day incubation. The inducible resistance to clarithromycin was maintained only in M. a. bolletii. Thus, the sequence analysis of the erm(41) gene can reliably identify the preservation of sensitivity to macrolides and serve as an important tool in the establishment of therapeutic regimens in cases of infections with M. abscessus.

Prevalence and Load of Cervical Ureaplasma Species With Respect to Intra-amniotic Complications in Women With Preterm Prelabor Rupture of Membranes Before 34 weeks.

Objectives: To determine the prevalence and load of Ureaplasma spp. DNA in the cervical fluid of women with singleton pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to intra-amniotic infection, sterile intra-amniotic inflammation, and colonization of the amniotic fluid. Methods: A total of 217 women with PPROM between gestational ages 24 + 0 and 33 + 6 weeks were included in this study. Paired amniotic and cervical fluid samples were collected at the time of admission via transabdominal amniocentesis and using a Dacron polyester swab, respectively. Microbial invasion of the amniotic cavity was diagnosed using a combination of culture and molecular biology methods. Intra-amniotic inflammation was determined based on the concentration of interleukin-6 in the amniotic fluid. Based on the presence or absence of these conditions, the women were stratified into the following subgroups: intra-amniotic infection (with both), sterile intra-amniotic inflammation (with inflammation only), colonization (with microorganisms only), and negative amniotic fluid (without either). The Ureaplasma spp. DNA load in the cervical fluid was assessed using PCR. Results: Ureaplasma spp. DNA in the cervical fluid was found in 61% (133/217) of the women. Women with negative amniotic had similar prevalence of Ureaplasma spp. DNA in cervical fluid (55%) to those with sterile intra-amniotic inflammation (54%) but lower than those with intra-amniotic infection (73%) and colonization (86%; p < 0.0001). Women with negative amniotic fluid had a lower load of Ureaplasma spp. DNA in their cervical fluid (median: 4.7 × 103 copies of DNA/ml) than those with intra-amniotic infection (median: 2.8 × 105 copies DNA/ml), sterile intra-amniotic inflammation (median: 5.3 × 104 copies DNA/ml), and colonization (median: 1.2 × 105 copies DNA/mL; p < 0.0001). Conclusion: In conclusion, in PPROM at <34 weeks, the presence of intra-amniotic infection, sterile intra-amniotic inflammation, or colonization of the amniotic fluid was associated with a higher prevalence and/or load of Ureaplasma spp. DNA in the cervical fluid than the absence of intra-amniotic complications.

Clinical characteristics of colonization of the amniotic cavity in women with preterm prelabor rupture of membranes, a retrospective study.

To determine the main clinical characteristics of preterm prelabor rupture of membranes (PPROM) complicated by colonization of the amniotic cavity (microbial invasion of the amniotic cavity without intra-amniotic inflammation). A total of 302 women with PPROM were included. Transabdominal amniocentesis was performed and amniotic fluid was assessed. Based of microbial invasion of the amniotic cavity and intra-amniotic inflammation (interleukin-6 ≥ 3000 pg/mL), the women were divided into following groups: intra-amniotic infection, sterile intra-amniotic inflammation, colonization of the amniotic cavity, and negative amniotic fluid. Colonization was found in 11% (32/302) of the women. The most common bacteria identified in the amniotic fluid were Ureaplasma spp. with a lower burden than those with intra-amniotic infection (p = 0.03). The intensity of intra-amniotic inflammatory response measured by interleukin-6 was higher in women with colonization than in those with negative amniotic fluid (medians: 961 pg/mL vs. 616 pg/mL; p = 0.04). Women with colonization had higher rates of acute inflammatory placental lesions than those with negative amniotic fluid. In PPROM, colonization, caused mainly by microorganisms from the lower genital tract, might represent an early stage of microbial invasion of the amniotic cavity with a weak intra-amniotic inflammatory response.

Long-Term Antibody Response and Vaccination Efficacy in Patients with COVID-19: A Single Center One-Year Prospective Study from the Czech Republic.

BACKGROUND: The diagnosis of SARS-CoV-2 is almost exclusively performed by PCR or antigen detection. The detection of specific antibodies has not yet been considered in official diagnostic guidelines as major laboratory evidence for a case definition. The aim the present study is to analyze antibody responses in outpatient and inpatient cohorts of COVID-19 patients in the Czech Republic over a 12-month period, and assess the potential of antibodies as a diagnostic tool. METHODS: A total of 644 patients was enrolled in the prospective study. IgA, IgM and IgG antibody levels, as well as virus neutralization titers, were analyzed over a 12-month period. RESULTS: Our study showed low antibody positivity levels at the admission. However, at 2 weeks after infection, 98.75% and 95.00% of hospitalized patients were IgA and IgG positive, respectively. Even in the outpatient cohort characterized by milder disease courses, the IgG antibody response was still sustained at 9 and 12 months. The data show a high correlation between the IgG levels and virus neutralization titers (VNTs). Samples from later time-points showed positive antibody responses after vaccination in both cohorts characterized by high IgG levels and VNT over 1:640. The samples from unvaccinated persons indicated a relatively high level of reinfection at 6.87%. CONCLUSIONS: Our results show that the detection of antibodies against the SARS-CoV-2 shows an increasing sensitivity from week 2 after infection and remains highly positive over the 12-month period. The levels of IgG antibodies correlate significantly with the VNTs. This suggests that the serological data may be a valuable tool in the diagnosis of SARS-CoV-2 infection.

Francisella tularensis caused cervical lymphadenopathy in little children after a tick bite: Two case reports and a short literature review.

Although Francisella (F.) tularensis is a well-described and understood zoonotic pathogen, its importance in Central Europe is relatively minor and, as such, tularaemia may be missed in the differential diagnosis. The annual incidence of tularaemia in the Czech Republic is relatively stable with up to 100 reported cases per year, except in the epidemic years 1998 and 1999 with 225 and 222 reported cases, respectively. It is, however, higher in comparison with the neighbouring countries. The common route of transmission in Central Europe is handling infected animals. Tularaemia is not commonly recognized as a tick-borne disease. Here we report two rare cases of a tick bite-associated ulceroglandular form of tularaemia in 2.5-year-old and 6.5-year-old children presenting with cervical lymphadenopathy. The unusual and interesting features of those cases are the young age and relatively uncommon route of transmission suggesting possible changes in the epidemiology of tularaemia in the Czech Republic. Therefore, the infection with F. tularensis should be considered in the differential diagnosis after a tick bite even in infants.

Intra-amniotic infection and sterile intra-amniotic inflammation in women with preterm labor with intact membranes are associated with a higher rate of Ureaplasma species DNA presence in the cervical fluid.

OBJECTIVE: To determine the prevalence of Ureaplasma spp. DNA and its load in the cervical fluid in women with preterm labor with intact membranes (PTL) complicated by intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation) or sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation alone). METHODS: Overall, 115 women with singleton pregnancies complicated by PTL between gestational ages of 22 + 0 and 34 + 6 weeks were included in this study. Paired amniotic and cervical fluid samples were collected at the time of admission via transabdominal amniocentesis using a Dacron polyester swab. Microbial invasion of the amniotic cavity was diagnosed based on a combination of culture and molecular biology methods. Intra-amniotic inflammation was determined based on the concentration of interleukin-6 in the amniotic fluid. Bacterial and Ureaplasma spp. DNA loads were assessed in the cervical fluid using PCR. RESULTS: Intra-amniotic infection and sterile inflammation were identified in 14% (16/115) and 25% (29/115) of the women, respectively. Ureaplasma spp. DNA in the cervical fluid was identified in 51% (59/115) of women. The presence of Ureaplasma spp. DNA in the cervical fluid was higher in women with intra-amniotic infection (75% (12/16)) and sterile intra-amniotic inflammation (76% (22/29)) than in women without intra-amniotic inflammation (36% (25/70); p = .0002). Concurrent presence of Ureaplasma spp. and Mycoplasma hominis DNA was higher in women with intra-amniotic infection (42% (5/12)) than women with sterile intra-amniotic inflammation (7% (2/29)) and women without intra-amniotic inflammation (7% (5/70); p = .001). There were no differences in the load of Ureaplasma spp. DNA in the cervical fluid among women with intra-amniotic infection, sterile intra-amniotic inflammation, and those without intra-amniotic inflammation (median values; infection: 1.2 × 104 copies DNA/mL; sterile: 5.0 × 105 copies DNA/mL; without: 8.4 × 104 copies DNA/mL; p = .18). CONCLUSIONS: In PTL , both forms of intra-amniotic inflammation were associated with a higher prevalence of Ureaplasma spp. DNA in the cervical fluid. The presence of intra-amniotic infection was related to a higher rate of concurrent Ureaplasma spp. and M. hominis DNA in the cervical fluid.

Preterm prelabor rupture of membranes without microbial invasion of the amniotic cavity and intra-amniotic inflammation: a heterogeneous group with differences in adverse outcomes.

OBJECTIVE: The absence of microbial invasion of the amniotic cavity and intra-amniotic inflammation at the time of hospital admission is the most common condition associated with preterm prelabor rupture of membranes (PPROM). Although the intensity of intra-amniotic inflammatory response does not exceed the threshold for the diagnosis of intra-amniotic inflammation in this subgroup of PPROM, whether there could be differences in outcomes concerning the intensity of intra-amniotic inflammatory response remains unclear. Therefore, the main aims of this study on PPROM without microbial invasion of the amniotic cavity and intra-amniotic inflammation were (i) to characterize the association between the intensity of intra-amniotic inflammatory response, measured according to amniotic fluid interleukin (IL)-6 concentrations, and the presence of acute histological chorioamnionitis and acute inflammation in the amnion; (ii) to characterize the association between the intensity of intra-amniotic inflammatory response and fetal inflammatory response, and (iii) to describe the short-term morbidity of infants based on the intensity of intra-amniotic inflammatory response. METHODS: This retrospective study included 131 women with singleton pregnancies with PPROM without microbial invasion of the amniotic cavity and intra-amniotic inflammation between gestational ages of 24 + 0 and 36 + 6 weeks and who had delivered within 72 h of membrane rupture. Microbial invasion of the amniotic cavity was assessed based on a combination of cultivation and non-cultivation methods. Intra-amniotic inflammation was characterized based on the amniotic fluid IL-6 concentration. In addition, a histopathological assessment of the placenta was performed. Fetal inflammatory response syndrome was characterized according to IL-6 concentration in the umbilical cord blood of >11 pg/mL. Based on the quartiles of IL-6 concentrations in the amniotic fluid, these women were divided into four subgroups (from the lowest to the highest IL-6 concentrations). RESULTS: IL-6 concentrations in amniotic fluid were higher in women with acute histological chorioamnionitis (median: 819 pg/mL vs. 520 pg/mL; p = .003) and with acute inflammation of the amnion (median: 1116 pg/mL vs. 533 pg/mL; p = .0002) than in women without these complications. The rates of acute histological chorioamnionitis and acute inflammation of the amnion were the highest in the subgroup with IL-6 concentrations above the 75th percentile in amniotic fluid (chorioamnionitis, p = .02; amnion, p = .0002). No differences in IL-6 concentrations in amniotic fluid were identified between women with and without a fetal inflammatory response syndrome (p = .40). The rate of fetal inflammatory response syndrome did not vary among the amniotic fluid IL-6 quartile subgroups of women. Moreover, no differences were noted in short-term neonatal outcomes among the amniotic fluid IL-6 quartile subgroups. CONCLUSION: A higher intensity of the intra-amniotic inflammatory response, measured by amniotic fluid IL-6 concentrations, is associated with a higher rate of acute inflammatory lesions in the placenta in the subset of PPROM pregnancies without microbial invasion of the amniotic cavity and intra-amniotic inflammation.

Strong Antimicrobial and Healing Effects of Beta-Acids from Hops in Methicillin-Resistant Staphylococcus aureus-Infected External Wounds In Vivo.

Staphylococcus (S.) aureus is an important causative agent of wound infections with increasing incidence in the past decades. Specifically, the emergence of methicillin-resistant S. aureus (MRSA) causes serious problems, especially in nosocomial infections. Therefore, there is an urgent need to develop of alternative or supportive antimicrobial therapeutic modalities to meet these challenges. Purified compounds from hops have previously shown promising antimicrobial effects against MRSA isolates in vitro. In this study, purified beta-acids from hops were tested for their potential antimicrobial and healing properties using a porcine model of wounds infected by MRSA. The results show highly significant antimicrobial effects of the active substance in both the powder and Ambiderman-based application forms compared to both no-treatment control and treatment with Framycoin. Moreover, the macroscopic evaluation of the wounds during the treatment using the standardized Wound Healing Continuum indicated positive effects of the beta-acids on the overall wound healing. This is further supported by the microscopic data, which showed a clear improvement of the inflammatory parameters in the wounds treated by beta-acids. Thus, using the porcine model, we demonstrate significant therapeutic effects of hops compounds in the management of wounds infected by MRSA. Beta-acids from hops, therefore, represent a suitable candidate for the treatment of non-responsive nosocomial tissue infections by MRSA.

Strong Antimicrobial Effects of Xanthohumol and Beta-Acids from Hops against Clostridioides difficile Infection In Vivo.

Clostridioides (C.) difficile is an important causative pathogen of nosocomial gastrointestinal infections in humans with an increasing incidence, morbidity, and mortality. The available treatment options against this pathogen are limited. The standard antibiotics are expensive, can promote emerging resistance, and the recurrence rate of the infection is high. Therefore, there is an urgent need for new approaches to meet these challenges. One of the possible treatment alternatives is to use compounds available in commonly used plants. In this study, purified extracts isolated from hops-alpha and beta acids and xanthohumol-were tested in vivo for their inhibitory effect against C. difficile. A rat model of the peroral intestinal infection by C. difficile has been developed. The results show that both xanthohumol and beta acids from hops exert a notable antimicrobial effect in the C. difficile infection. The xanthohumol application showed the most pronounced antimicrobial effect together with an improvement of local inflammatory signs in the large intestine. Thus, the hops compounds represent promising antimicrobial agents for the treatment of intestinal infections caused by C. difficile.

Heterogeneity of post-COVID impairment: interim analysis of a prospective study from Czechia.

We stratified post-COVID patients into four newly established clinical groups based on the presence or absence of at least one subjective respiratory symptom and at least one objective sign of pulmonary involvement. Nearly half of outpatients and one third of hospitalized post-COVID patients had objective signs of pulmonary involvement without accompanying subjective respiratory symptoms three months after diagnosis.

IgGFc-binding protein in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study.

To determine the IgGFc-binding protein (FcgammaBP) concentration in amniotic and cervical fluids in preterm prelabor rupture of membranes (PPROM) and preterm labor with intact membranes (PTL) and to assess the diagnostic indices of FcgammaBP to predict intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation). In this study, we included 170 and 79 women with PPROM and PTL, respectively. Paired cervical and amniotic fluid samples were obtained using a Dacron polyester swab and transabdominal amniocentesis, respectively. The FcgammaBP concentrations in the samples were assessed using an enzyme-linked immunosorbent assay. The presence of intra-amniotic infection was associated with elevated FcgammaBP concentrations in pregnancies with PPROM and PTL [PPROM-presence: 86 ng/mL vs. absence: 13 ng/mL, p < 0.0001, area under receiver operating characteristic curve (AUC) = 0.94; PTL-presence: 140 ng/mL vs. absence: 22 ng/mL, p < 0.0001, AUC = 0.86]. In cervical fluid, the concentrations of FcgammaBP were elevated in the presence of intra-amniotic infection in pregnancies with PPROM only (presence: 345 ng/mL vs. absence: 60 ng/mL, p < 0.0001, AUC = 0.93). FcgammaBP in amniotic fluid might be a marker of intra-amniotic infection in women with both PPROM and PTL However, in cervical fluid, it is only observed in women with PPROM.

The wide-spectrum antimicrobial effect of novel N-alkyl monoquaternary ammonium salts and their mixtures; the QSAR study against bacteria.

Quaternary ammonium salts (QASs) have been widely used for disinfection purposes because of their low price, high efficacy and low human toxicity for decades. However, precise mechanisms of action nor the powerful versatile agent against all antimicrobial species are known. In this study we have prepared 43 novel N-alkyl monoquaternary ammonium salts including 7 N,N-dialkyl monoquaternary ammonium salts differing bearing alkyl chain either of 12, 14 or 16 carbons. Together with 15 already published QASs we have studied the antimicrobial efficacy of all water-soluble compounds together with standard benzalkonium salts against Gram-positive (G+) and Gram-negative (G-) bacteria, anaerobic spore-forming Cl. difficile, yeasts, filamentous fungi and enveloped Varicella zoster virus (VZV). To address the mechanism of action, lipophilicity seems to be a key parameter which determines antimicrobial efficacy, however, exceptions are likely to occur and therefore QSAR analysis on the efficacy against G+ and G- bacteria was applied. We showed that antibacterial activity is higher when the molecule is larger, more lipophilic, less polar, and contains fewer oxygen atoms, fewer methyl groups bound to heteroatoms or fewer hydrogen atoms bound to polarized carbon atoms. In addition, from an application point of view, we have formulated mixtures, on the basis of obtained efficiency of individual compounds, in order to receive wide-spectrum agent. All formulated mixtures completely eradicated tested G+ and G- strains, including the multidrug-resistant P. aeruginosa as well as in case of yeasts. However, effect on A. fumigatus, Cl. difficile and VZV the exposition towards mixture resulted in significant reduction only. Finally, 3 out of 4 formulated mixtures were safer than reference commercial agent based on benzalkonium salts only in the skin irritation test using reconstructed human epidermidis.