Infection Research Articles

Immune Response to SARS-CoV-2 in Vaccine-naive Pregnant Women: Assessment of IgG and IgA Antibody Profile at Delivery and 42 Days Postpartum.

This prospective cohort study assessed the SARS-CoV-2 IgG and IgA Ab profiles at delivery and 42 d postpartum in unvaccinated SARS-CoV-2-positive pregnant women and determined the association with the timing and the clinical course of the infection. A total of 387 vaccine-naive women with confirmed SARS-CoV-2 infection during pregnancy were included. IgG and IgA Abs were detected in maternal blood at delivery and 42 d postpartum using ELISA kits. The relationships between Ab detection and value and clinical features, including the timing of the infection, were analyzed using univariate and multivariate logistic and linear regression models. The mean gestational age at infection was 31 4/7 wk of pregnancy. Symptoms of SARS-CoV-2 infection were present in 88.1% of women. IgG and IgA Abs were detected in 45.7 and 58.9% at delivery, respectively, increasing to 72.7 and 76.8% at 42 d postpartum. Detection of IgG and IgA Abs in maternal blood at delivery was independently associated with symptomatic infection (adjusted odds ratio [OR] 3.13, 95% confidence interval (CI): 1.47-6.69 and adjusted OR 3.62, 95% CI: 1.8-7.26, respectively), but not with the time from positive swab to delivery or gestational age at positive swab. Detection of Abs at 42 d postpartum was also strongly associated with the detection of Abs at delivery (OR 29.97, 95% CI: 10.11-88.82 for IgG and OR 13.09, 95% CI: 6.37-26.9 for IgA). Vaccine-naive pregnant women exhibit a significant and durable immune response to SARS-CoV-2, which is more pronounced in symptomatic women but independent of gestational age at diagnosis or the diagnosis-to-delivery interval.

Development and Preliminary Validation of a Central Venous Access Device-Associated Skin Impairment Classification Tool Using Modified Delphi and Clinimetric Methods.

An evidence and consensus-based instrument is needed to classify central venous access device-associated skin impairments. The aim of this study was to design and evaluate the central venous access device-associated skin impairment classification tool. A two-phase modified Delphi study. This two-phase study consisted of a literature review, followed by the development and validation of a classification instrument, by experts in the fields of central venous access devices and wound management (Phase 1). The instrument was tested (Phase 2) using 38 clinical photographs of a range of relevant skin impairments by the same expert panel. The expert panel consisted of registered nurses who were clinical researchers (n = 4) and clinical experts (n = 3) with an average of 24 years of nursing and research experience and 11 years of experience in wound management. Measures to assess preliminary content validity and inter-rater reliability were used. The instrument consists of five overarching aetiological classifications, including contact dermatitis, mechanical injury, infection, pressure injury and complex clinical presentation, with 14 associated subcategory diagnoses (e.g., allergic dermatitis, skin tear and local infection), with definitions and signs and symptoms. High agreement was achieved for preliminary scale content validity and item content validity (I-CVI = 1). Inter-rater reliability of aetiologies was high. The overall inter-rater reliability of individual definitions and signs and symptoms had excellent agreement. The development and preliminary validation of this classification tool provide a common language to guide the classification and assessment of central venous access device-associated skin impairment. The comprehensive and validated classification tool will promote accurate identification of central venous access device-associated skin impairment by establishing a common language for healthcare providers. The availability of this tool can reduce clinical uncertainty, instances of misdiagnosis and the potential for mismanagement. Consequently, it will play a pivotal role in guiding clinical decision-making, ultimately enhancing the quality of treatment and improving patient outcomes. The Guidance on Conducting and Reporting Delphi Studies (CREDES) was adhered to. No patient or public contribution.

Green synthesis of polyethylene glycol coated, ciprofloxacin loaded CuO nanoparticles and its antibacterial activity against Staphylococcus aureus

Antibacterial resistance requires an advanced strategy to increase the efficacy of current therapeutics in addition to the synthesis of new generations of antibiotics. In this study, copper oxide nanoparticles (CuO-NPs) were green synthesized using Moringa oleifera root extract. CuO-NPs fabricated into a form of aspartic acid-ciprofloxacin-polyethylene glycol coated copper oxide-nanotherapeutics (CIP-PEG-CuO) to improve the antibacterial activity of NPs and the efficacy of the drug with controlled cytotoxicity. These NPs were charachterized by Fourier transform infrared spectroscopy (FTIR), x-rays diffraction spectroscopy (XRD), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Antibacterial screening and bacterial chemotaxis investigations demonstrated that CIP-PEG-CuO NPs show enhanced antibacterial potential against Gram-positive and Gram-negative clinically isolated pathogenic bacterial strains as compared to CuO-NPs. In ex-vivo cytotoxicity CIP-PEG-CuO-nano-formulates revealed 88% viability of Baby Hamster Kidney 21 cell lines and 90% RBCs remained intact with nano-formulations during hemolysis assay. An in-vivo studies on animal models show that Staphylococcus aureus were eradicated by this newly developed formulate from the infected skin and showed wound-healing properties. By using specially designed nanoparticles that are engineered to precisely transport antimicrobial agents, these efficient nano-drug delivery systems can target localized infections, ensure targeted delivery, enhance efficacy through increased drug penetration through physical barriers, and reduce systemic side effects for more effective treatment.

Comparison of Infection Rate Between Sterile and Nonsterile Gloves During Mohs Micrographic Surgery: An Updated Systematic Review and Meta-Analysis.

Mohs micrographic surgery (MMS) is a well-established technique for the removal of various types of skin cancers. While sterile gloves (SG) are commonly used in skin surgeries such as MMS, additional understanding of their effectiveness compared to nonsterile gloves (NSG) in preventing local infection is required. We aimed to perform an updated systematic review and meta-analysis comparing the use of SG with NSG for local infection rate post-MMS and point out cost discrepancies between these 2 scenarios. We searched MEDLINE, Embase, and Cochrane for studies published up to August 2023 comparing the use of SG with NSG during MMS that reported the outcome of wound infection. A total of 4 studies with 10,644 MMS were included, of which 7512 (70.6%) were performed with SG and 3132 (29.4%) were done with NSG. In the SG group, 232 out of 7512 cases (3.1%) developed infection compared to 64 out of 3132 (2.0%) in the NSG group [odds ratio (OR) 1.14; 95% confidence interval (CI) 0.85-1.52; P = .39; I2 = 0%]. Therefore, the post-MMS infection rates were not significantly different between SG and NSG groups, including in the excision (OR 0.92; 95% CI 0.48-1.79; P = .81; I2 = 0%) and reconstruction (OR 1.17; 95% CI 0.85-1.60; P = .34; I2 = 0%) subanalysis. Regarding the mean cost of the gloves, the NSG pair was $0.24, approximately 10% of the price of the SG pair ($2.27). The results support that, compared to SG, NSG are equally effective in preventing infections during MMS while offering significant cost savings without compromising patient outcomes.Protocol registration: PROSPERO, CRD42023458525.

The [99mTc]Tc-HMPAO-labelled white blood cell SPECT/CT as a novel criterion for infective endocarditis diagnosis

Aims: Infective endocarditis (IE) poses a significant clinical challenge, necessitating nuanced diagnostic tools for early and accurate detection. The diagnostic role of the hybrid technique of single-photon emission tomography-computed tomography with technetium-99 m-hexamethylpropyleneamine oxime–labelled leukocytes ([99mTc]Tc-HMPAO-SPECT/CT) has evolved in recent years. This single-center study assessed whether the recent inclusion in the 2023 European Society of Cardiology modified diagnostic criteria of IE (2023 ESC) of infectious lesions detected with [99mTc]Tc-HMPAO-SPECT/CT affects their diagnostic performance.Methods and results: Between 2015 and 2019, we enrolled 205 consecutive adults with suspected IE. All participants underwent [99mTc]Tc-HMPAO-SPECT/CT scans (370–740 MBq). Scans were deemed positive in the presence of intracardiac abnormal tracer uptake and/or within the cardiac implantable electronic device. Patients were prospectively followed-up for 12 ± 10 months. Local device infection (LDI) or IE was diagnosed in 75 (36.6 %) patients, while 72 (35.1 %) [99mTc]Tc-HMPAO-SPECT/CT results returned positive. Moreover, extracardiac infectious foci were detected in 25 % of [99mTc]Tc-HMPAO-SPECT/CT scans. The inclusion of both intracardiac and extracardiac lesions detected with [99mTc]Tc-HMPAO-SPECT/CT yields significantly higher sensitivity (p = 0.003) and negative predictive value (NPV) (p = 0.009).Conclusion: The inclusion of [99mTc]Tc-HMPAO-SPECT/CT into the IE diagnostic work-up improves the appropriate classification of patients. For patients with IE, the extended inclusion of lesions detected with [99mTc]Tc-HMPAO-SPECT/CT in the ESC 2023 diagnostic criteria significantly improves sensitivity and NPV while reducing potential IE misdiagnoses. This pioneering imaging modality is poised to become an integral component of clinical practice, promising to advance IE diagnosis and management.

Genotypic and phenotypic characterisation of asymptomatic bacteriuria (ABU) isolates displaying bacterial interference against multi-drug resistant uropathogenic E. Coli

Escherichia coli can colonise the urogenital tract of individuals without causing symptoms of infection, in a condition referred to as asymptomatic bacteriuria (ABU). ABU isolates can protect the host against symptomatic urinary tract infections (UTIs) by bacterial interference against uropathogenic E. coli (UPEC). The aim of this study was to investigate the genotypic and phenotypic characteristics of five ABU isolates from midstream urine samples of adults. Comparative genomic and phenotypic analysis was conducted including an antibiotic resistance profile, pangenome analysis, and a putative virulence profile. Based on the genome analysis, the isolates consisted of one from phylogroup A, three from phylogroup B2, and one from phylogroup D. Two of the isolates, PUTS 58 and SK-106-1, were noted for their lack of antibiotic resistance and virulence genes compared to the prototypic ABU strain E. coli 83,972. This study provides insights into the genotypic and phenotypic profiles of uncharacterised ABU isolates, and how relevant fitness and virulence traits can impact their potential suitability for therapeutic bacterial interference.

Incidence of symptomatic Borrelia burgdorferi sensu lato infection in Romania, 2018−2023

BackgroundLyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. Although public health surveillance for LB has been conducted in Romania since 2007, the extent of under-detection of Bbsl infections by LB surveillance has not been estimated. We therefore estimated the under-detection of symptomatic Bbsl infections by LB surveillance to better understand the LB burden in Romania.MethodsThe number of incident symptomatic Bbsl infections were estimated from a seroprevalence study conducted in six counties (population 2.3 M) and estimates of the symptomatic proportion and duration of persistence of anti-Bbsl immunoglobulin G (IgG) antibodies. The number of incident symptomatic Bbsl infections were compared with the number of surveillance-reported LB cases to derive an under-detection multiplier, and then the under-detection multiplier was applied to LB surveillance data to estimate the incidence of symptomatic Bbsl infection from 2018 to 2023.ResultsWe estimate that there were 1968 individuals with incident symptomatic Bbsl infection in the six counties where the seroprevalence study was conducted in 2020, compared with the 187 surveillance-reported LB cases, resulting in an under-detection multiplier of 10.5 (i.e., for every surveillance-reported LB case, there were 10.5 symptomatic incident Bbsl infections). The incidence of symptomatic Bbsl infection in the six counties was 86.9/100,000 population in 2023, similar to the incidence in 2018−2020 (86.0) and higher than in 2021−2022 (40.3).ConclusionsThere is a higher incidence of symptomatic Bbsl infection than is reported through public health surveillance for LB in Romania. Additional efforts are needed to strengthen disease prevention and address the important public health problem of LB.Graphic

Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance.

Enterovirus-D68 (EV68) has emerged as a global health concern over the last decade with severe symptomatic infections resulting in long-lasting neurological deficits and death. Unfortunately, there are currently no FDA-approved antiviral drugs for EV68 or any other non-polio enterovirus. One particularly attractive class of potential drugs are small molecules inhibitors, which can target the conserved active site of EV68-3C protease. For other viral proteases, we have demonstrated that the emergence of drug resistance can be minimized by designing inhibitors that leverage the evolutionary constraints of substrate specificity. However, the structural characterization of EV68-3C protease bound to its substrates has been lacking. Here, we have determined the substrate specificity of EV68-3C protease through molecular modeling, molecular dynamics (MD) simulations, and co-crystal structures. Molecular models enabled us to successfully characterize the conserved hydrogen-bond networks between EV68-3C protease and the peptides corresponding to the viral cleavage sites. In addition, co-crystal structures we determined have revealed substrate-induced conformational changes of the protease which involved new interactions, primarily surrounding the S1 pocket. We calculated the substrate envelope, the three-dimensional consensus volume occupied by the substrates within the active site. With the elucidation of the EV68-3C protease substrate envelope, we evaluated how 3C protease inhibitors, AG7088 and SG-85, fit within the active site to predict potential resistance mutations.

Congenital cytomegalovirus and pulmonary hypertension.

Lung involvement in children with congenital cytomegalovirus infection has been scarcely described. We describe three new cases of persistent pulmonary hypertension in children with congenital cytomegalovirus and review the other seven cases reported in the literature since 1988. All children had a symptomatic infection, including severe central nervous system or visceral findings. Morbidity and mortality were high. Persistent pulmonary hypertension may be a rare complication in severely symptomatic congenital cytomegalovirus infants. It is important to screen for congenital cytomegalovirus in cases of idiopathic refractory persistent pulmonary hypertension. Intensive treatment should be undertaken to treat this potentially rare lung involvement in combination with antiviral treatment.

Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection.

Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed. Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir. Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL-1 of ganciclovir was calculated. The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.

Cat Scratch Disease in Pediatrics: Who Has Systemic Involvement?

Bartonella henselae is the agent responsible for cat scratch disease (CSD). Although lymphadenopathy is typically the defining symptom, some patients develop potentially severe systemic compromise. It is unknown why some patients progress to systemic disease. The objective of this study was to describe the clinical, epidemiologic and laboratory characteristics of children with CSD and to analyze the differences between systemic versus localized infections. Patients were identified by a retrospective review of medical records at a tertiary pediatric care hospital in Buenos Aires, Argentina, from January 2012 to July 2021. A CSD case was defined as any patient who presented compatible clinical findings with a positive serologic test (IgG >1/64 or IgM immunofluorescence) for B. henselae. A total of 197 patients were identified, with a median age of 8 years (range: 1-17.4 years). The most frequent clinical symptoms were fever and lymphadenopathy. Systemic involvement was present in 34.5% (n = 68) of patients and the most common presentation was splenic abscess (n = 51), followed by liver abscess (n = 23), chorioretinitis (n = 9), osteomyelitis (n = 5) and pneumonitis (n = 3). Patients with invasive disease more frequently presented with fever (79.4% vs. 50.3%) (P<0.001) and had higher C-reactive protein levels (24.9 vs. 6.7 mg/L) (P<0.001). Antibiotic therapy was administered to 95.9% (n = 187) of patients and most with systemic disease (77%) used combination treatment. Most patients recovered fully, and there were no reported deaths. CSD must be considered a potential cause of lymphadenopathy. Patients with fever and elevated C-reactive protein should be evaluated to rule out systemic compromise.

Salivary glands - a new site of Helicobacter pylori occurrence.

The role of Helicobacter pylori (Hp) in the pathological processes of the gastric mucosa is well understood. Decreasing trend in successful eradication of HP from the stomach was observed in last years. This lack of succes is mainly caused by increasing ATB resistance. Nevertheless other possible causes of this phenomenon are being explored. Thus, many studies have focused on the search for extragastric reservoirs as potential sources of persistence or reinfection after successful Hp eradication. The pathological potential of Hp at these localities has also been studied. Our study aimed to determine the presence of Hp inside the salivary glands ductal system through its detection from sialolites. Subsequently, we tried to prove the possible ability of Hp to penetrate the salivary gland parenchyma by detecting Hp from the tissue of salivary tumors. Concrements and salivary tumor tissue samples were collected using sialendoscopy or standard surgery, and Hp detection and genotyping were performed through PCR. Hp was detected in 68.3% of the sialopathy samples. VacA S1AM1 was the most common genotype. CagA-positive genotype represented only 34% of the total number of positive samples. Our findings of Hp positivity in concrements provide compelling evidence of Hp presence in the ductal system of salivary glands. Confirmation of Hp presence in tumor tissue suggests its potential ability to infiltrate the gland's parenchyma. Further research is needed to confirm Hp's ability to cause local infection, as well as the possible causal association between Hp presence in the studied region, sialolithiasis, and salivary gland tumors.

Facial Artery Perforator Flap for Perioral and Perinasal Oncologic Defect Reconstruction: Surgical Technique and Postoperative Outcomes.

Facial artery perforator (FAP) flap is a versatile and reliable one-step facial reconstruction technique. However, its full potential remains underutilized due to a lack of clear guidelines and rigorous technique requirements. This study report the use of FAP flaps in our centre for the management of perioral and nasal oncologic defects, focusing on surgical technique performed and post-operative management. We conducted a retrospective review of all patients who underwent reconstruction with a perioral or perinasal FAP flap only following tumor resection over a 4-year period (n = 29). Parameters measured included flap survival, complication rates, surgical technique performed, and the need for touch-up procedures. Patients were grouped based on age, defect size, and location and outcomes were compared across these groups. The mean histological tumor defect area was 331 mm2. During at least 6 months of follow-up, no local recurrence was observed. Twenty-seven (93.1%) flaps survived completely. Major postsurgical complications occurred in seven (23.8%) patients, including complete flap necrosis (1), partial flap necrosis (1), flap collapse (1), venous congestion (1), wound dehiscence (1), and local infection (2). A higher complication rate was associated with nose tip defects (80.0% vs. 12.5%, p = 0.007). Touch-up procedures were more frequently required for reconstructions involving the nasal sidewall and dorsum (53.8% vs. 13.3%, p = 0.04). Based on our experience, the FAP flap is highly effective for the reconstruction of the upper lip, nasolabial fold, and certain oncologic nasal defects. However, specific defect locations, such as the nose tip, may be associated with higher complication rates, necessitating careful patient selection and surgical planning.

Are important predictors of adverse outcome in children with symptomatic congenital cytomegalovirus infection overlooked in clinical settings?

Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations. This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years. Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes. Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late.

The Surfactant Properties of Clindamycin as a Useful Adjunct for Removing Ruptured Silicone Implants.

Silicone gel removal after breast implant rupture is a difficult task. Silicone is hydrophobic and thus cannot be irrigated effectively with saline. Attempts at mechanical removal with sponges are often partially successful. Incomplete removal results in persistent silicone contamination with possible local inflammation, infection, and silicone granulomata. In this partially quantitative investigation, we assess the de-adhesion ability of different clindamycin formulations against known surfactant controls when combined with silicone gel. To demonstrate surfactant properties in vitro, clindamycin phosphate, clindamycin hydrochloride, and a known surfactant, sodium dodecyl sulfate (SDS), were compared. An amount of 170 g of silicone gel placed in a dry glass container exhibited strong adherence to the container walls. In separate trials, clindamycin phosphate (300 mg in 100 mL), clindamycin HCl (300 mg in 100 mL), and SDS (1 g in 100 mL) solutions with normal saline were added to the silicone aggregate, and de-adhesion properties were compared. All solutions aided in the de-adhesion of the sticky silicone from glass substrate. The SDS had the strongest effect, followed by clindamycin phosphate and then clindamycin HCl. The observed interactions suggested that all of the solutions behaved as ionic surfactant coating the silicone with negative charges via adsorption. However, the phosphate anionic formulation was associated with a greater surfactant effect than HCl. Clindamycin acts as a surfactant to aid in the clinical removal of ruptured silicone gel. Clindamycin phosphate seems to have a stronger effect than clindamycin HCl, likely related to the negative charges on the phosphate groups.

Feasibility and Effectiveness of Venoarterial Extracorporeal Membrane Oxygenation Plus Intra-Aortic Balloon Pump Assisted High-Risk Percutaneous Coronary Intervention in Complex Coronary Disease.

Mechanical circulatory support may facilitate high-risk percutaneous coronary intervention (PCI). This study aimed to assess the feasibility, safety and effectiveness of high-risk PCI under the support of venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with intra-aortic balloon pump (IABP). We enrolled patients who received VA-ECMO plus IABP-assisted PCI procedures at our center from April 2012 to June 2018. Major adverse cardiac events (MACEs) included all-cause death, myocardial infarction, and target vessel revascularization. A total of 10 patients were included, with a mean age of 71 years, EuroSCORE II of 19.9%, and SYNTAX score of 39.8. Procedural success was achieved in nine (90%) patients. The mean duration of ECMO support was 1.5 hours, and 2.6 stents were implanted per patient. Major complications included contrast-induced nephropathy needing hemodialysis in one (10%) patient, significant hemoglobin drop requiring blood transfusion in two (20%) patients, pulmonary infection in one (10%) patient, and local surgical incision infection in one (10%) patient. The accumulative mortality rates for the nine patients with procedural success were 0, 22.2%, and 44.4% at 1, 3, and 5 years follow-up, respectively. However, cardiac death occurred in only one (11.1%) patient. In addition, two patients received repeat PCI or coronary artery bypass grafting within two years following the index procedure. The overall incidence rates of MACEs were 11.1%, 44.4%, and 66.7% at 1, 3, and 5 years follow-up, respectively. VA-ECMO plus IABP-assisted high-risk PCI was feasible in patients with complex coronary disease, with a high procedural success rate and acceptable mid-term clinical outcomes.

Generation of singlet oxygen inside living cells: correlation between phosphorescence decay lifetime, localization and outcome of photodynamic action

Photodynamic therapy (PDT) is a promising alternative treatment for localized lesions and infections, utilizing reactive oxygen species (ROS) generated by photosensitizers (PS) upon light activation. Singlet oxygen (1O2) is a key ROS responsible for photodynamic damage. However, the effectiveness of PS in biological systems may not correlate with the efficiency of singlet oxygen generation in homogeneous solutions. This study investigated singlet oxygen generation and its decay in various cellular microenvironments using liposome and ARPE-19 cell models. Rose Bengal (RB), methylene blue (MB), and protoporphyrin IX (PpIX) were employed as selected PS. Lifetimes of singlet oxygen generated by the selected photosensitizers in different cellular compartments varied, indicating different quenching rates with singlet oxygen. RB, located near cell membranes, exhibited the highest phototoxicity and lipid/protein peroxidation, followed by PpIX, while MB showed minimal cytotoxicity in similar conditions. Singlet oxygen decay lifetimes provide insights into PS localization and potential phototoxicity, highlighting the importance of the lipid microenvironment in PDT efficacy, providing useful screening method prior to in vivo applications.Graphical abstract

Immune response in vaccinated healthcare workers with frequent COVID-19 infections is characterised by blunted IFNγ and IL-2 responses to SARS-CoV-2 variants

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. Despite widespread vaccination, some HCWs develop frequent symptomatic infection. We hypothesised that HCWs with frequent symptomatic COVID-19 have impaired T and B cell mediated immunity to SARS-CoV-2.Vaccinated HCWs with no prior COVID infection (n = 9), asymptomatic recent infection (n = 10), and frequent recent infection (n = 15) were recruited from a longitudinal HCW cohort study. Whole blood stimulation with SARS-CoV-2 variants (Wuhan, B.1.617, BA.2, BA.2.75, BA.4/5, XBB.1.5, BQ.1.1) was performed, with IFNγ and IL-2 responses, total IgG produced, and anti-Spike antibody neutralising capacity measured.Frequent infections had similar IFNγ and IL-2 responses to the never infected group, with significantly higher responses in the asymptomatic group. The frequent cohort had higher IgG responses to Delta and BA.4/5 and higher neutralising capacity against Omicron variants. An immune signature of blunted IL-2 and IFNγ in frequent infections may identify HCWs at increased risk of further infection.

The oculomotor cistern and pituitary adenomas: anatomical and clinical study.

The oculomotor cistern (OMC) is a meningeal cuff filled with CSF that contains the oculomotor nerve (cranial nerve [CN] III) at the level of the lateral wall of the cavernous sinus. Only a few studies have investigated the involvement of the OMC by pituitary adenomas (pituitary neuroendocrine tumors [PitNETs]), mainly with relatively small case series. The aim of this study was to perform a histomorphological description of the OMC and systematically analyze its involvement by PitNETs from radiological, clinical, and surgical perspectives. Ten hemisellae from formalin-fixed specimens were studied with 3-µm sections. Digital image analysis software was used for morphological and quantitative assessments. Clinical, radiological, surgical, and histological data of patients undergoing endoscopic transsphenoidal surgery for PitNETs at the University of Brescia, Italy, between 2014 and 2021 were recorded. OMC involvement was graded as not compressed, compressed, and invaded. The same surgical team operated on all patients. The OMC had an elliptical shape with an average area of 3.1 mm2 and a length of 5.5 mm. No cisternal points of weakness were recognized in the histomorphological study. Of 315 patients, 246 had complete data: apoplexy and CN III palsy were documented in 6.9% and 8.5%, respectively. OMC compression and invasion were recorded in 106 (43.1%) and 23 (9.3%) patients. Significant associations between OMC involvement and PitNET dimensions (p < 0.001), Knosp grade (p < 0.001), preoperative oculomotor palsy (p < 0.001), Ki-67 percentage (p = 0.009), and recurrence/progression of residual tumor (p = 0.008) were found. A new postoperative CN III palsy was evident in 2%: transient in 4 cases, and persistent in 1 patient treated for a recurrent PitNET who experienced a local infection complication. Preoperative CN III palsy improved in 10 cases. Significant OMC involvement by PitNETs might be underrecognized, but it can be treated using the endoscopic transsphenoidal approach, and it affects patient outcomes.

Efficacy of Calcium Sulfate Antibiotic Carriers in the Treatment of Severe Infections of the Temporal Bone

Objective: To study the additional use of topical antibiotic-loaded calcium sulfate pellets in difficult-to-treat cases of temporal bone infections. Patients: Four patients with advanced and pretreated temporal bone disease. Intervention: Application of topical antibiotic-loaded calcium sulfate pellets following surgical debridement in infections of the temporal bone. Main Outcome Measures: Reinfection- and revision-free follow-up analysis and assessment of audiometric data. Results: A total of 4 patients were included (3 females and 1 male, mean age of 29.5 years [SD 19.8]). All patients (4/4) had a revision-free follow-up during a mean of 24.5 (SD, 6.19) months. Reinfections (n = 3) were observed in 2 patients (2/4) occurring 1 and 15, as well as 8 months after surgery. Reinfections could be successfully treated using topically and/or orally applied antibiotic therapy. No change in air-conducted pure-tone average was observed after treatment (mean change 1.3 dB; P = 0.99). Conclusion: Local application of antibiotic-loaded calcium sulfate pellets in combination with surgical debridement represents an effective treatment for local infection control in difficult-to-treat cases of temporal bone infections.