[Chronic rhinosinusitis with nasal polyposis : A retrospective analysis of therapeutic approaches in 463 patients]. / Chronische Rhinosinusitis mit Polyposis nasi : Retrospektive Analyse des therapeutischen Vorgehens bei 463 Patienten.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease, the treatment of which has undergone significant changes in recent years. In addition to surgical approaches, topical and systemic steroids, and adaptive acetylsalicylic acid (ASA) desensitization, three specific antibodies have complemented the therapeutic portfolio since 2019. METHODS: A retrospective evaluation of all patients who presented as outpatients for the first time due to CRSwNP in 2007 and 2008 (collective A) and 2017 and 2018 (collective B) was performed, up to and including June 2023. RESULTS: The clinical courses of 463 patients (mean age 49.1 years, range 5-82 years; 65.9% male) were included in the analysis. Conservative treatment with nasal corticosteroids started before initial presentation was more frequent in collective B (collective A 43.9% vs. collective B 72.2%). In 278 of the 463 patients (60%; A: 62%, B: 58%), at least one operation on the nasal sinuses had been performed after initial presentation; in 101 of these patients (36.3%) recurrent polyposis (within mean follow-up of 2.4 years) required further treatment. The indication for ASA provocation/desensitization was applied less frequently in collective B, also due to a high discontinuation rate (at least 38%) of the maintenance therapy. Of the total cohort, 16 patients (3.5%; A: n = 8, B: n = 8) were meanwhile switched to antibody therapy at recurrence. CONCLUSION: A step-by-step guideline-orientated approach is recommended in the treatment of CRSwNP. Systemic antibodies as an add-on to nasal corticosteroids are a relatively new therapeutic option for treatment-refractory CRSwNP, which reduces the indication for ASA desensitization, which is associated with a relatively high incidence of side effects and poor compliance.

[Chronic rhinosinusitis with nasal polyps-extension of dupilumab treatment intervals]. / Chronische Rhinosinusitis mit nasalen Polypen ­ Verlängerung der Dupilumab-Therapieintervalle.

BACKGROUND: In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300 mg every 2 weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24 weeks, reducing the dose of dupilumab to once every 4 weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended. METHODS: The course of 29 patients with severe CRSwNP, type­2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300 mg, the dupilumab interval had been prolonged individually, initially up to 4 weeks, thereafter up to 6 weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany). RESULTS: All patients showed an excellent improvement within the first 3 months. The dupilumab application interval was extended to 4 weeks after 7-31 months (median 13 months) and to 6 weeks (n = 9) after 17-35 months (median 23 months). No recurrent polyps or symptoms were subsequently observed. CONCLUSION: In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to 4 and potentially 6 weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential.

Continuous investigation of the nasal cycle over 48 hours.

BACKGROUND: Previous results on the nasal cycle refer to measurements over up to 24h. The long-term rhinoflowmetry (LRFM) allows continuous observations over a longer period. The aim of the study was to observe the nasal cycle for the first time over 48h under everyday conditions. METHODOLOGY: The LRFM was continuously applied to 30 rhinologically healthy subjects (20 female, 10 male) over 48h. The different types of nasal cycle were classified as follows: "classic", "in concert", "one-sided", "no-cycle" and "mixed". The focus of this study was on the results over the entire 48 hours. The comparison of the two consecutive days was also made. RESULTS: A nasal cycle could be detected in 100% of the subjects over 48h. With 97%, the mixed type most commonly occurred as a combination of classical and in concert components. In all subjects, classical cycle components could be detected at least once. The no-cycle type was not observed. In the awake state, the mixed type dominated (80%), as a combination of classical and in concert parts. In the sleep state, the classical type was the most common type (97%). The average phase duration was 206 ± 83 minutes. CONCLUSIONS: In the very first continuous 48-hour study on the nasal cycle, 100% of the subjects presented a nasal cycle. The LRFM method is the only one that offers the possibility to perform continuous measurements over a longer period during daily routine. The results of previous single-stage examination methods should thus be questioned.

[Typical emergencies in otorhinolaryngology-a monocentric analysis of the seasonal course]. / Typische Notfälle in der Hals-Nasen-Ohren-Heilkunde ­ eine monozentrische Evaluation über den jahreszeitlichen Verlauf.

BACKGROUND: The incidence of acute ear, nose, and throat (ENT) diagnoses is influenced by multiple parameters, for example meteorological and seasonal influences. By better understanding the triggering factors, prophylactic approaches can be developed. MATERIALS AND METHODS: A retrospective analysis was performed over 6 years of all patients who presented to the university hospital because of typical and minor ENT emergencies. The diagnoses impacted cerumen, acute otitis media, acute otitis externa, nasal bone fracture, epistaxis, acute tonsillitis, acute rhinosinusitis, and peritonsillar abscess were analyzed. RESULTS: A total of 32,968 cases were analyzed. Epistaxis was the most common of the investigated emergency diagnoses, accounting for 24.5% (8082 cases). Epistaxis, acute otitis media, and acute rhinosinusitis occurred significantly more frequently in the colder half of the year. There was no significant correlation of the incidence of nasal bone fracture with public holidays. Acute otitis externa correlated significantly with the local summer vacations. In calendar week 38, the fewest total emergency presentations occurred, whereas in calendar week 52, the most emergency presentations occurred. CONCLUSION: Seasonal and meteorological factors play a significant role in the pathogenesis of many emergency ENT diagnoses.

[Radicality of maxillary sinus surgery and size of the maxillary sinus ostium]. / Radikalität der Kieferhöhlenoperation und Größe des Kieferhöhlenfensters.

Until the 1990s, radical sinus surgery was considered a standard procedure for maxillary sinus diseases, but it is no longer favored due to the high morbidity. Today, functional endoscopic sinus surgery (FESS) is considered the gold standard in sinus surgery. Modifications of surgical approaches also allow access to regions of the maxillary sinus that were previously difficult to reach. Depending on anatomy and pathology, different methods for widening the maxillary ostium can be selected. In type I sinusotomy, the natural ostium is widened dorsally by a maximum of 1 cm. Sinusotomy type II involves widening the natural ostium up to a maximum diameter of 2 cm. In sinusotomy type III, the natural ostium is widened dorsally to the posterior wall of the maxillary sinus and caudally to the base of the inferior turbinate. Beside the prelacrimal approach, more invasive approaches are the medial maxillectomy, in which the dorsal part of the inferior turbinate and the adjacent medial wall of the maxillary sinus is resected, as well as its modifications "mega antrostomy" and "extended maxillary antrostomy." Correct selection of the size of the maxillary sinus window is prerequisite for successful treatment and long-term postoperative success. Isolated purulent maxillary sinusitis can usually be treated by a type I sinusotomy. Sinusotomy type II addresses nasal polyps with involvement of the mucosa of the ostium, recurrent stenosis after previous surgery, chronic maxillary sinusitis due to cystic fibrosis, and purulent maxillary sinusitis with involvement of other adjacent sinuses. Sinusotomy type III is required for choanal polyps with attachment to the floor of the maxillary sinus, for extensive polyposis and fungal sinusitis, and for inverted papilloma. Particularly for (recurrent) disease and extensive interventions in the maxillary sinus, medial maxillectomy or a modification thereof may be required.

[Oncoimmunology in old age]. / Onkoimmunologie im Alter.

Physiological aging processes of the immune system are associated with an increased susceptibility to infectious, autoimmune and tumor diseases. In accordance with the general demographic development the number of tumor patients in advanced age also increases. An end to this development is not yet foreseeable. In tumor treatment, immunotherapy with checkpoint inhibitors is becoming increasingly more important; however, only a few studies on the efficacy and side-effect profiles in older patients exist so far. In this review article the changes in the immune system in old age and the influence on carcinogenesis are discussed. In addition, the current state of research on the immunotherapy of patients in advanced age who suffer from head and neck cancer is presented.

A hippocampus to prefrontal cortex neural pathway inhibits food motivation through glucagon-like peptide-1 signaling.

The hippocampus and the medial prefrontal cortex (mPFC) are traditionally associated with regulating memory and executive function, respectively. The contribution of these brain regions to food intake control, however, is poorly understood. The present study identifies a novel neural pathway through which monosynaptic glutamatergic ventral hippocampal field CA1 (vCA1) to mPFC connectivity inhibits food-motivated behaviors through vCA1 glucagon-like peptide-1 receptor (GLP-1R). Results demonstrate that vCA1-targeted RNA interference-mediated GLP-1R knockdown increases motivated operant responding for palatable food. Chemogenetic disconnection of monosynaptic glutamatergic vCA1 to mPFC projections using designer receptors exclusively activated by designer drugs (DREADDs)-mediated synaptic silencing ablates the food intake and body weight reduction following vCA1 GLP-1R activation. Neuropharmacological experiments further reveal that vCA1 GLP-1R activation reduces food intake and inhibits impulsive operant responding for palatable food via downstream communication to mPFC NMDA receptors. Overall these findings identify a novel neural pathway regulating higher-order cognitive aspects of feeding behavior.

Pharmacokinetic changes of antibiotic, antiviral, antituberculosis and antifungal agents during extracorporeal membrane oxygenation in critically ill adult patients.

WHAT IS KNOWN AND OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a life-saving system used for critically ill patients with cardiac and/or respiratory failure. The pharmacokinetics (PK) of drugs can change in patients undergoing ECMO, which can result in therapeutic failure or drug toxicity requiring further management of drug complications. In this review, we discussed changes in the PK of antibiotic, antiviral, antituberculosis and antifungal agents administered to adult patients on ECMO. These drugs are crucial for managing infections, which commonly occur during ECMO. METHODS: A literature search was conducted using the PubMed and EMBASE databases with the following keywords: "extracorporeal membrane oxygenation OR extracorporeal membrane oxygenations OR ECMO" and "PK OR pharmacokinetics OR pharmacokinetic*" and "anti infective* OR antibiotic* OR antiviral* OR antituberculosis OR antifungal*." RESULTS AND DISCUSSION: Generally, the volume of distribution (Vd) increases and drug clearance (CL) and elimination decrease during ECMO. Highly significant changes in drug PK can occur by interactions with the ECMO device itself, drug characteristics, pathological changes and patient characteristics. This may affect the blood concentrations of drugs, which influence the success of therapy. The PK of vancomycin, piperacillin-tazobactam, meropenem, azithromycin, amikacin and caspofungin did not change significantly in adult patients receiving ECMO. However, there were significant changes in the PK of imipenem, oseltamivir, rifampicin and voriconazole. The trough concentrations of imipenem were highly variable; oseltamivir had a decreased CL and increased Vd, and rifampicin concentrations were below therapeutic levels, even when a higher-than-standard dose was used in patients treated with ECMO. Additionally, voriconazole exhibited high mean peak concentrations during ECMO. WHAT IS NEW AND CONCLUSION: The impact of ECMO on PK varies among drugs in adult patients, and there is no consistent correlation between the effects observed in adult and infant studies. This review suggested that doses of imipenem, oseltamivir, rifampicin and voriconazole should be adjusted and therapeutic drug monitoring is needed when ECMO is used in adult patients. In the future, large PK trials in adults on ECMO are needed to provide optimal dosing guidelines. A PK/PD modelling approach will be useful for determining the precise impact of ECMO and other factors that contribute to PK changes for each drug. Finally, it is important to develop dosing guidelines based on PK/PD modelling studies that can be used in clinical practice.

Respiratory syncytial virus-associated hospitalizations over three consecutive seasons in children with congenital heart disease.

The purpose of this investigation was to analyze the burden of respiratory syncytial virus (RSV)-related hospitalizations in infants and children with congenital heart disease (CHD) over three consecutive RSV seasons. Retrospectively, all children with hemodynamically significant (HS-CHD) and not significant (HNS-CHD) CHD born between 2004 and 2008 at a tertiary care university hospital and identified by ICD-10 diagnoses were included. Data on RSV-related hospitalizations over the first three years of life covering at least three RSV seasons (November-April) were analyzed. The overall incidence of RSV-related hospitalization was 9.6 % (58/602), without a statistically significant difference between HS-CHD and HNS-CHD (7.3 % vs. 10.4 %; p = 0.258). Recommendation of palivizumab prophylaxis did not influence the RSV hospitalization rates between groups. Patients with HS-CHD and early surgery were significantly less often hospitalized due to RSV compared to those with delayed surgery (1.3 % vs. 14.3 %; p = 0.003). The median duration of hospitalization was 8.5 days (HS-CHD: 14 vs. HNS-CHD: 7 days; p = 0.003). Thirteen patients (22.4 %) were admitted to the intensive care unit (ICU), for a median of 10 days. The median age at admission was 2 months, with a significant difference between HS-CHD and HNS-CHD (6 vs. 2 months; p = 0.001). The majority (97 %) of RSV-related hospitalizations occurred before 12 months of age. Patients with HS-CHD had a significantly more severe course of RSV disease and were older at the time of hospitalization. Early surgery seemed to significantly reduce the risk of RSV hospitalization during the first RSV season.

High Resolution Strain Analysis Comparing Aorta and Abdominal Aortic Aneurysm with Real Time Three Dimensional Speckle Tracking Ultrasound.

OBJECTIVE/BACKGROUND: Ultrasound measurement of aortic diameter for aneurysm screening allows supervision of aneurysm growth. Additional biomechanical analysis of wall motion and aneurysm deformation can supply information about individual elastic properties and the pathological state of the aortic wall. Local aortic wall motion was analyzed through imaged aortic segments according to age and pathology. METHODS: Sixty-five patients were examined with a commercial four dimensional ultrasound system (4D-US). Three groups were defined: patients with normal aortic diameter and younger than 60 years of age (n = 21); those with normal aortic diameter and older than 60 years of age (n = 25); and those with infrarenal aortic aneurysm (n = 19). A diastolic reference shape of aortic wall segments was obtained and local and temporally resolved wall strain was determined. Indices characterizing the resulting wall strain distribution were determined. RESULTS: The analysis of biomechanical properties displayed increasing heterogeneous and dyssynchronous circumferential strain with increasing patient age. Young patients exhibited higher mean strain amplitude. The distribution of the spatial heterogeneity index and local strain ratio was inversely proportional to age. The maximum local strain amplitude was significantly higher in the young (0.26 ± 0.17) compared with the old (0.16 ± 0.07) or aneurysmal aorta (0.16 ± 0.10). Temporal dyssynchrony significantly differed between young (0.13 ± 0.10) and old (aneurysmal 0.31 ± 0.04, non-aneurysmal 0.29 ± 0.05), regardless of aortic diameter. The spatial heterogeneity index and local strain ratio differentiate non-aneurysmal and aneurysmal aorta, regardless of age. CONCLUSIONS: 4D-US strain imaging enables description of individual wall motion (kinematics) of the infrarenal aorta with high spatial and temporal resolution. Functional differences between young, old, and aneurysmal aorta can be described by mean (circumferential) strain amplitude, the spatial heterogeneity index, and the local strain ratio. Further investigation is required to refine this new perspective of patient individualized characterization of the pathological AAA wall and eventually to rupture risk stratification.

Periodontitis impacts quality of life in postmenopausal women.

AIM: Interrelationships between traditional dental variables are becoming more evident in far-reaching aspects of life such as psychosocial interaction, self-esteem, overall health and even occupational performance. This study compares quality of life in postmenopausal women with chronic periodontitis with that of healthy postmenopausal women. METHOD: A total of 128 randomly recruited postmenopausal women received a comprehensive periodontal evaluation and completed the Utian Quality of Life Survey. The participants were divided into healthy and periodontitis groups based on comprehensive periodontal examination. Mean scores were calculated for each quality-of-life item, domain and the overall summary score. Periodontitis patients' quality-of-life outcomes were compared to those of healthy patients using the t-test with threshold of significance at p < 0.05. RESULTS: Quality-of-life scores in all fields measured were significantly poorer in the periodontitis patients compared to the healthy patients, occupational (25.74 ± 8.25 vs. 21.40 ± 9.19), health (26.46 ± 5.93 vs. 19.64 ± 10.24), emotional (21.04 ± 10.20 vs. 16.40 ± 10.84), sexual (9.23 ± 4.92 vs. 5.96 ± 5.20), and total score (82.48 ± 23.74 vs. 63.69 ± 26.61). CONCLUSION: This study has identified that postmenopausal women with chronic periodontitis report significantly poorer quality of life than healthy patients. Clinicians caring for postmenopausal women should be aware that periodontitis also impacts quality of life when making referral decisions for oral health care.

Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.

The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.

Effects of Exposure to Welding Fume on Lung Function: Results from the German WELDOX Study.

The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker's lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15% of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.

[Bradykinin-induced angioedema: Definition, pathogenesis, clinical presentation, diagnosis and therapy]. / Bradykinininduzierte Angioödeme: Definition, Pathogenese, Klinik, Diagnose und Therapie.

The incidence of bradykinin-induced angioedema is considerably lower than that of histamine-induced forms; however, the same is true for the clinician's knowledge of this condition. Bradykinin-induced angioedemas include hereditary angioedema (HAE), as well as acquired forms induced by drugs or antibody formation, e.g., during the course of oncologic disease. Drug-induced forms affect almost exclusively the head and neck region, and are thus important for the otorhinolaryngologist. Clear differentiation between histamine-induced angioedema (e. g., connected to allergy/urticaria) and bradykinin-induced angioedema is essential for selection of the specific treatment and may be lifesaving. Antihistamines and cortisone derivatives have no relevant effect in bradykinin induced-angioedema, whereas blood-derived C1 esterase inhibitor and bradykinin receptor 2 antagonists represent effective therapeutic options--both for acute and prophylactic treatment.

[Outpatient Surgery in German ENT in Teaching Hospitals--Economic Nonsense?]. / Ambulante Operationen in HNO-Ausbildungskliniken - ökonomischer (Un)sinn?

INTRODUCTION: There is an ever-increasing demand to increase efficiency and decrease costs in health care. This leads to an growing number of outpatient surgeries which are less cost effective. Especially in the setting of university teaching hospitals, this may lead to both an undersupply of qualified physicians, as well as to a worsening of clinical training of residents. In order to quantify a possible undersupply and estimate the expense of teaching residents, the time for medical procedures needs to be quantified and compared between board-certified physicians and residents. This was the aim of the current study. MATERIAL AND METHODS: All outpatient adenotomies of children with or without paracentesis or tympanic drainage insertion performed in 2012 in 2 ENT teaching hospitals were analyzed. The length of the surgical procedure as well as the level of training of the surgeon was analyzed. Operating times of residents in training were analyzed stratified by training level and then compared to operation times of board-certified ENT surgeons. RESULTS: 255 procedures were analyzed. Significant differences of the mean operation time could be identified depending on the level of training of residents compared to board-certified ENT surgeons for all investigated training levels. E. g. 1(st) year residents' surgeries required 2.4 times more time than those of board-certified ENT surgeons. CONCLUSION: Based on an analysis of outpatient ENT-surgical procedures it becomes apparent that due to the extended operating times of residents in training outpatient surgery is by far less cost-effective than by board-certified physicians. To cope with the demand of teaching residents for their clinical training, more resources are necessary in the setting of teaching hospitals.

Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

Retrospective genome-oriented analysis reveals low transmission rate of multidrug-resistant Pseudomonas aeruginosa from contaminated toilets at a bone marrow transplant unit.

BACKGROUND: Prevention of toilet-to-patient transmission of multidrug-resistant Pseudomonas aeruginosa (MDR PA) poses management-related challenges at many bone marrow transplant units (BMTUs). AIM: To conduct a longitudinal retrospective analysis of the toilet-to-patient transmission rate for MDR PA under existing infection control (IC) measures at a BMTU with persistent MDR PA toilet colonization. METHODS: The local IC bundle comprised: (1) patient education regarding IC; (2) routine patient screening; (3) toilet flushing volume of 9 L; (4) bromination of toilet water tanks, and (5) toilet decontamination using hydrogen peroxide. Toilet water was sampled periodically between 2016 and 2021 (minimum every three months: 26 intervals). Upon MDR PA detection, disinfection and re-sampling were repeated until ≤3 cfu/100 mL was reached. Whole-genome sequencing (WGS) was performed retrospectively on all available MDR PA isolates (90 out of 117 positive environmental samples, 10 out of 14 patients, including nine nosocomial). FINDINGS: WGS of patient isolates identified six sequence types (STs), with ST235/CT1352/FIM-1 and ST309/CT3049/no-carbapenemase being predominant (three isolates each). Environmental sampling consistently identified MDR PA ST235 (65.5% ST235/CT1352/FIM-1), showing low genetic diversity (difference of ≤29 alleles by core-genome multi-locus sequence typing (cgMLST)). This indicates that direct toilet-to-patient transmission was infrequent although MDR PA was widespread (detection on 79 occasions, detection in every toilet). Only three MDR PA patient isolates can be attributed to the ST235/CT1352/FIM-1 toilet MRD PA population over six years. CONCLUSION: Stringent targeted toilet disinfection can reduce the potential risk for MDR PA acquisition by patients.

Case report: Sustained complete remission with all-oral MEPED therapy in a patient with Hodgkin's disease developing resistance to pembrolizumab.

Targeted chemotherapy and immune checkpoint inhibitors (ICPi) have expanded the spectrum of therapies for patients with relapsed/refractory (r/r) Hodgkin's disease and significantly improved the proportion of patients with long-term disease control. However, there is no standardized therapeutic option in case of further progression. Recently, we demonstrated that therapy with MEPED (metronomic chemotherapy, everolimus, pioglitazone, etoricoxib, dexamethasone) is highly effective in patients with r/r Hodgkin's disease. The benefit after pre-treatment with ICPi has not been studied, yet. Here, we report a patient with progressive Hodgkin's disease on Pembrolizumab for the first time who achieved sustained complete remission (CR) after initiation of MEPED therapy. A 57-year-old patient was pre-treated with brentuximab vedotin for relapsed advanced Hodgkin's disease and had received Pembrolizumab for progression from November 2020 to July 2022. Due to further progression, MEPED therapy was started in August 2022 and continued until May 2023. It consisted of a strictly oral daily (28-day cycle) application of low-dose treosulfan 250 mg, everolimus 15 mg, pioglitazone 45 mg, etoricoxib 60 mg, and dexamethasone 0.5 mg. Treatment response was evaluated by F-18 FDG-PET/CT (PET/CT). CR was defined by a negative Deauville score (DS) of 1-3. Already 3 months after starting MEPED, a CR (DS: 3) was confirmed by PET/CT in November 2022. The next follow-up in May 2023 continued to show CR (DS: 3). The therapy was very well tolerated. No hematological or other organ toxicity was observed. However, in May 2023 the patient presented with leg edema and weight gain, most likely due to pioglitazone and the PET/CT revealed suspected everolimus-induced pneumonitis, so MEPED was discontinued and diuretic therapy and treatment with prednisolone was started with gradual dose reduction. This resulted in a rapid complete resolution of the symptoms. The next PET-CT in July 2023 continued to show CR (DS: 3) without evidence of pneumonitis. Currently, therapy with MEPED has not been resumed. In conclusion, we demonstrate for the first time that MEPED therapy is highly effective in a patient with Hodgkin's disease who has been refractory to ICPi. Sustained CR was achieved over 11 months after initiation of MEPED therapy. Further studies on a larger patient cohort should be performed.

Aspergillus PCR-based investigation of fresh tissue and effusion samples in patients with suspected invasive Aspergillosis enhances diagnostic capabilities.

Although it is a severe complication in immunocompromised patients, diagnosing invasive fungal disease (IFD), especially invasive aspergillosis (IA), remains difficult. In certain clinical scenarios, examining tissue samples for identification of the infectious organism becomes important. As culture-based methods rarely yield results, the performance of an Aspergillus-specific nested PCR in fresh tissue or pleural effusion samples was evaluated. Fresh tissue (n = 59) and effusion (n = 47) specimens from 79 immunocompromised patients were subjected to an Aspergillus-specific PCR assay. Twenty-six patients had proven (n = 20) or probable (n = 6) IFD, according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, while the remaining patients were classified as having either possible IFD (n = 30) or no IFD (n = 23). IA was identified as the underlying IFD in 21/26 proven/probable cases. PCR positivity was observed for 18/21 proven/probable and 6 possible IA cases; cases classified as no IA did not show positive signals. Patients with proven IFD (n = 5) with cultures positive for non-Aspergillus molds also had negative Aspergillus PCR results. Aspergillus PCR performance analysis yielded sensitivity and specificity values of 86% (95% confidence interval [CI], 65% to 95%) and 100% (95% CI, 86% to 100%), respectively, thus leading to a diagnostic odds ratio of >200. In this analysis, good diagnostic performance of the PCR assay for detection of IA was observed for tissue samples, while effusion samples showed lower sensitivity rates. PCR testing represents a complementary tool; a positive PCR result strengthens the likelihood of IA, whereas IA seems unlikely in cases with negative results but findings could indicate non-Aspergillus IFD. Thus, PCR testing of these specimens enhances the diagnostic capabilities.

Prevalence of, and factors associated with, alcohol use disorder among young adults (aged 15-24 years) living with HIV/AIDS in low-income and middle-income countries: protocol for a systematic review.

INTRODUCTION: Alcohol use is a global driver of HIV infection and disease progression, mediated through risky behaviour and poor antiretroviral adherence. Most studies about the burden of alcohol use among people living with HIV (PLWH)/AIDS have been done in adult populations, but less is known about young people with HIV, especially in low-income and middle-income countries (LMICs), despite the high level of alcohol use in these settings. The aim of this review is to collate evidence on the prevalence of, and factors associated with, alcohol use disorder (AUD) among young adults (aged 15-24 years) living with HIV/AIDS in LMICs. METHODS AND ANALYSIS: Two experienced librarians will conduct an independent article search in PubMed, PsycINFO, Embase and Web of Science databases, using relevant Medical Subject Headings terms and Boolean operators ('AND', 'OR'). We will include English-language articles that were published in peer-reviewed journals from 1 January 2000, to 25 July 2022, that documented the prevalence of AUD among young people (15-24 years) living with HIV in LMICs. We shall exclude systematic review articles and qualitative studies. Two independent reviewers will screen the articles for eligibility and data will be extracted onto a preset Excel spreadsheet. Data analysis will be done using Stata V.14.0. Heterogeneity will be assessed by use of the I2 statistic and data will be pooled in meta-analyses where appropriate. Publication bias will be assessed using the funnel plot. ETHICS AND DISSEMINATION: Ethical approval is not needed as this systematic review will be based on published studies. Findings from this study will be disseminated via submission for publication in a peer-reviewed journal, at conference presentations, and made available to health professionals, scientists and policy makers. Our data set can be made available on request. REGISTRATION DETAILS: PROSPERO, CRD42022308955.