Overview of pharmacotherapy targeting COVID-19 disease based on ACE-2: current challenges and future directions.

The new Severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) triggered the pandemic of COVID-19, which is currently still ongoing. In 2021 a worldwide vaccine campaign was launched, and in parallel the lines of research are continuing to target the most effective drug therapies for the treatment of COVID-19 disease. SARS-CoV­2 enters host cells via glycoprotein angiotensin-converting enzyme 2 (ACE-2), which plays a major role in renin-angiotensin system interactions and undergoes changes in expression during metabolic and viral diseases, including COVID-19. It seems that the severe lung damage that occurs in several cases of COVID-19 disease may be connected to a deregulated expression of ACE­2. In this manuscript we focus on the line of research that studies the pharmacological modification of ACE­2 expression, a promising weapon to counter the severe harms caused by COVID-19.

[Primary tuberculosis of the cavum: An unusual diagnosis]. / Tuberculose primitive du cavum : un diagnostic peu commun.

Primary tuberculosis of the cavum is a rare entity. It can occur at any age, especially between the second and ninth decade. We report the case of a 17-years-old patient with nasal obstruction and left laterocervical adenomegaly. A cervico-facial CT scan showed a suspicious looking tumor process of the nasopharynx. Histological analysis of the biopsies taken showed chronic granulomatous inflammation with necrosis and the absence of tuberculosis lesions in the usual sites, especially the lungs, led to the diagnosis of primary tuberculosis of the cavum. There was a good evolution on antituberculosis drugs. This unusual location can be a source of difficulties and delay in diagnosis, especially because of the clinical presentation, which suggests a nasopharyngeal tumour. In developing countries, where this disease remains relatively endemic, cross-sectional imaging techniques and histopathological analysis are of great interest for the management of patients.

[Web search data as health data? : Geographic differences, temporal trends, and topics of interest from internet search engine analyses in Germany]. / Websearch-Daten als Gesundheitsdaten? : Geografische Unterschiede, zeitliche Trends und Interessenschwerpunkte von Internetsuchmaschinenanfragen in Deutschland.

BACKGROUND: Limited timely, cost-effective, and regional availability of healthcare data is considered one of the limiting factors for timely analyses in the field of health services research and thus for healthcare delivery to the general population. Thus, Internet search engine analyses are coming into focus in this context. OBJECTIVES: What contribution can data on the volume of Internet searches for various diseases make to the health care of the German population? Where is the potential and where are the limitations? METHODS: A review of the current literature and a selective overview of Internet search engine analyses of dermatological, allergological, and infectious diseases published in the last 4 years in Germany were performed. RESULTS: By analyzing web search data, temporal developments such as seasonality, months with the highest interest, and geographical differences can be mapped at the national, state (Bundesländer), and city level and major points of interest (e.g., skin cancer of the eye or anal itching) regarding a certain health topic can be identified. In addition, some studies were able to show correlations between search volume and external factors (e.g., temperature, care structure) and to registered cases (e.g., skin cancer, Lyme disease). CONCLUSION: Web search data, given the limitations noted, are able to directly provide spatiotemporal mapping regarding the needs of the Internet-using population. They are particularly useful in situations where traditional health data are limited or unavailable.

New reporter zebrafish line unveils heterogeneity among lymphatic endothelial cells during development.

BACKGROUND: In zebrafish, lymphatic endothelial cells (LECs) originate from multiple/several distinct progenitor populations and generate organ-specific lymphatic vasculatures. Cell fate and tissue specificities were determined using a combination of genetically engineered transgenic lines in which the promoter of a LEC-specific gene drives expression of a fluorescent reporter protein. RESULTS: We established a novel zebrafish transgenic line expressing eGFP under the control of part of the zebrafish batf3 promoter (Basic Leucine Zipper ATF-Like Transcription Factor 3). Spatiotemporal examination of Tg(batf3MIN:eGFP) transgenic fish revealed a typical lymphatic expression pattern, which does not perfectly recapitulate the expression pattern of existing LEC transgenic lines. eGFP+ cells constitute a heterogeneous endothelial cell population, which expressed LEC and/or blood endothelial cells (BEC) markers in different tissues. In addition, we characterize the renal eGFP+ cell as a population of interest to study kidney diseases and regeneration. CONCLUSION: Our Tg(batf3MIN:eGFP) reporter zebrafish line provides a useful system to study LEC populations, of which heterogeneity depends on origin of progenitors, tissue environment and physiological conditions. We further developed a novel fish-adapted tissue clearing method, which allows deep imaging and 3D-visualization of vascular and lymphatic networks in the whole organism.

Sporadic Creutzfeldt-Jakob Disease: A Retrospective Analysis of 104 Cases.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019. METHODS: A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations. RESULTS: In the 104 sCJD patients, pathological evidence of a spongiform change was found in 11 patients, while the remaining 93 patients were probable sCJD. The 104 patients included 57 males and 47 females, with the age of onset ranging from 29 to 82 (mean: 58, median: 60) years. The time from disease onset to death ranged from 1 to 36 months. Most of the patients died 7-12 months after the onset of sCJD. In most patients, rapidly progressive dementia appeared as the initial symptom, followed by cerebellar ataxia, visual disturbances, and neurobehavioral disorders. Most patients' DWI images showed symmetric or asymmetric hyperintensity in the cortex. In terms of EEGs, 38.2% of the patients had periodic sharp wave complexes. The sensitivity of 14-3-3 protein detection was 34.1%. The brain PET scans of 50 patients with sCJD presented 96% sensitivity for the diagnosis of sCJD. CONCLUSIONS: This study indicated that sCJD occurred at an early age in patients in China. The sensitivity of 14-3-3 protein detection was significantly low, but brain PET was highly sensitive in the diagnosis of sCJD.

Are infectious diseases and microbiology new fields for thermal therapy research?

Antimicrobial chemotherapy and surgery are classical methods for treating infectious diseases. However, there is a need for alternative methods to cure infections caused by antibiotic-resistant pathogens, recurrent or chronic infections, and unreachable local infections in which the use of drugs or surgery is anatomically and physically restricted. Several micro-organisms are known to be sensitive to mild hyperthermia, and this sensitivity is one of the potential benefits proposed for the host during an episode of fever. Additionally, some immunological or biophysical changes occur during hyperthermia. These changes may be useful for eliminating thermo-susceptible microbial pathogens using local heat therapy. There are several experimental studies proposing the use of hyperthermia to treat local infections. The infected organs or tissues may be heated up to a temperature that can inhibit invading microorganisms. Here, it is hypothesised that local heat therapy may become an alternative or adjuvant method for curing local infections. Here, we highlight the potential for local hyperthermia in the treatment of bacterial infections caused by thermo-susceptible pathogens in a systematic plan. If the proposed thermal-microbiology concepts and local thermal therapies can be adapted to clinical microbiology and infectiology, new medical fields, such as thermo-microbiology and thermo-infectiology, may be created in the future.

Evidence of non-linearity in the association of glycemic control with influenza/pneumonia mortality: a study of 19 000 adults from the US general population.

BACKGROUND: Diabetes is a major public health problem and thought to be a risk factor for infectious diseases, but pertinent epidemiological evidence is limited. This study aimed to analyse the associations of diabetes, disease duration and glycated haemoglobin levels (HbA1c) with infectious diseases mortality in the general population, including the investigation of potential non-linear relationships. METHODS: An observational, prospective study of 19 783 subjects included in the Third National Health and Nutrition Examination Survey, representing the adult non-institutionalized population of the United States of America, was conducted. The analysis was done by multiple Cox regression and restricted cubic spline modelling. RESULTS: Self-reported diabetes and diabetes duration were not significantly associated with the outcomes. However, there was evidence for a non-linear association of HbA1c with mortality from influenza, pneumonia or other acute lower respiratory infections. Spline regression suggested a roughly doubled risk of mortality beyond an HbA1c of 6.5% (48 mmol/mol) in reference to 5.2% (33 mmol/mol). CONCLUSIONS: Future studies on diabetes and infections should adequately address potential non-linearity, which may be necessary to better understand and characterize more precisely the relationship of diabetes with infectious diseases.

[Mycosis caused by Nannizzia incurvata in a traveler returning from Indonesia]. / Mykose durch Nannizzia incurvata bei einem Reiserückkehrer aus Indonesien.

Nannizzia incurvata is a geophilic dermatophyte that is rarely detected in Germany. We report on a 17-year-old traveler returning from Indonesia in whom Nannizzia incurvata was isolated as the causative agent of tinea corporis. Targeted, local antimycotic therapy and clinical follow-up was recommended. This report shows the importance of a detailed travel history and targeted mycological diagnostic workup.

Improving the Care of Severe, Open Fractures and Postoperative Infections of the Lower Extremities: Protocol for an Interdisciplinary Treatment Approach.

BACKGROUND: Patients with open fractures often experience complications during their injury. The treatments incur high costs. Interdisciplinary cooperation between different medical disciplines may improve treatment outcomes. Such cooperation has not yet been envisaged in the German health care system. OBJECTIVE: The aim of the study is to improve the treatment of fractures with open soft tissue damage or postoperative complications in terms of duration and sustainability in a region in northwest Germany. Largely standardized diagnostics and therapy are intended to optimize processes in hospitals. In addition, a reduction in the duration of treatment and treatment costs is to be achieved. METHODS: Using a digital platform, physicians from 31 hospitals present patient cases to an interdisciplinary group of experts from the fields of plastic surgery, infectiology, hygiene, and others. The group of experts from the environment of the University Hospital Münster promptly makes a joint treatment recommendation for the individual case. The plan is to examine 3300 patients with open fractures or surgical complications. As consortium partners, there are also 3 statutory health insurance companies. The extent to which the therapy recommendations are effective and contribute to cost reduction in the health care system will be empirically investigated in a stepped-wedge cluster-randomized design. In addition, medical and nonmedical professional groups involved in the project will be asked about their work in the project (in total, 248 clinic employees). The primary outcome is the complication rate of open fractures or the occurrence of postoperative complications. As secondary outcomes, the number of antibiotics administered, limb function, and quality of life will be assessed. The health economic evaluation refers to the costs of health services and absenteeism. For the work-related evaluation, workload, work engagement, work-related resources, readiness for technology, and ergonomic aspects of the new telemedical technology will be collected. In addition, clinic employees will give their assessments of the success of the project in a structured telephone interview based on scaled and open-ended questions. RESULTS: The project started in June 2022; data collection started in April 2023. As of mid-June 2024, data from 425 patients had been included. In total, 146 members of staff had taken part in the questionnaire survey and 15 had taken part in the interviews. CONCLUSIONS: Standardized treatment pathways in the standard care of patients with open fractures and postoperative infections will be established to reduce complications, improve chances of recovery, and reduce costs. Unnecessary and redundant treatment steps will be avoided through standardized diagnostics and therapy. The interdisciplinary treatment perspective allows for a more individualized therapy. In the medium term, outpatient or inpatient treatment centers specialized in the patient group could be set up where the new diagnostic and therapeutic pathways could be competently applied. TRIAL REGISTRATION: German Clinical Trials Register DRKS00031308; https://drks.de/search/de/trial/DRKS00031308. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57820.

Ulcerating vulvar lesions revealing a rare female case of monkeypox in Switzerland.

The human monkeypox virus is a zoonotic orthopoxvirus initially discovered in Africa that causes a disease similar to smallpox with less severe symptoms. Since May 2022, the virus is being transmitted from human to human at an increasing rate outside of Africa. Although monkeypox infection was endemic in Africa, it had sporadic surges in recent years. This has led the World Health Organization to declare its highest alert level on July 25, 2022. In Switzerland only, 456 individuals have been diagnosed with monkeypox infection from May 19, 2022, to August 29, 2022. To date, >99% of patients with monkeypox infection are men, in particular those who have sex with other men. Clinical cases of women with monkeypox infection are still very rare but will more likely be seen. With this case, we have highlighted the fact that this zoonosis is also starting to spread among women. We have presented the case of a female patient living in Switzerland who presented to our gynecologic emergency department for painful vulvar lesions after an episode of upper respiratory tract infection. The monkeypox infection was confirmed with a real-time polymerase chain reaction analysis at the University Hospital of Geneva, a center of reference for monkeypox in Switzerland. Shortly after, the patient developed generalized and typical lesions on the whole body.

Possible association of urinary incontinence with post-COVID-19: a report of three cases.

INTRODUCTION: The disorder denominated urinary incontinence (UI) has been diagnosed amongst 25-45% of women worldwide. Muscle weakness is one of the more notable symptoms, which is exhibited in the acute form of coronavirus disease 2019 (COVID-19) that compromises the respiratory musculature. Accordingly, this report aims to delineate three cases in women with UI possibly associated with post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE REPORTS: Three elderly Brazilian women expressed UI symptomology post-COVID-19 recovery. In the investigation reports, there was no documented acute impairment or hospitalization post-COVID-19. Nevertheless, some form of UI derived from muscle weakness was detected and treated by physiotherapy in these patients. The patient 1 (P1) was classified as mixed urinary incontinence (MUI) based on the presented symptomology during the filling phase and urinary leakage on exertion. Intravaginal probing suggested neural integrity. The P2 and P3 were classified as stress urinary incontinence (SUI), related to increased abdominal pressure. In all the three cases, there were benefits from physical therapy treatment. CONCLUSIONS: This case report is relevant in improving our understanding and lead to future research about the possibility of clinical variations as UI after infection by SARS COV 2 contributing to greater awareness in the diagnostic workup and allowing for earlier treatment and management. It is concluded that the surveillance of the distinct symptomologies associated with the SARS-CoV-2 infection is fundamental, because there is no adequate corroboratory evidence in the scientific literature, for the cases of pelvic floor muscles weakness that causes UI.

Impact of a clinical pharmacist's intervention on pneumococcal vaccination in a population of at- risk hospitalized patients: The IP-VAC study.

OBJECTIVES: The aim of this study was to evaluate the impact of clinical pharmacist intervention on compliance with pneumococcal vaccination (PV) recommendations in hospitalized patients. METHODS: This was a prospective, single-center, before-and-after study conducted in 2019-2020. Patients had to be over 18 years of age, at risk of pneumococcal infection, and with no PV. No changes were made in the observational phase. During the interventional phase, the clinical pharmacist discussed a prescription for preventive PV and a mention in the discharge letter. A pharmaceutical consultation sensitized the patient to the interest of PV. The clinical pharmacist ensured that a complete vaccination protocol would be carried out by the retail pharmacist within 3 months of hospitalization. RESULTS: One hundred and sixty-seven (167) patients were included. In the observational phase, 2.3% of patients received a complete vaccination protocol after discharge from primary care. The rate increased to 63.8% after the clinical pharmacist's intervention (p < 0.001). Vaccines were prescribed by hospital physicians in 97.5% of cases, while 40% of discharge letters included the indication for PV. CONCLUSION: The clinical pharmacist's intervention led to delivery of a complete PV protocol after discharge for over half the patients. This study demonstrated the feasibility of a pharmaceutical intervention to promote PV in hospital activities.

Drug Delivery Systems for the Oral Administration of Antimicrobial Peptides: Promising Tools to Treat Infectious Diseases.

Antimicrobial peptides (AMPs) have a great potential to face the global expansion of antimicrobial resistance (AMR) associated to the development of multidrug-resistant (MDR) pathogens. AMPs are usually composed of 10-50 amino acids with a broad structural diversity and present a range of antimicrobial activities. Unfortunately, even if the oral route is the most convenient one, currently approved therapeutic AMPs are mostly administrated by the intravenous route. Thus, the development of novel drug delivery systems (DDSs) represents a promising opportunity to protect AMPs from chemical and enzymatic degradation through the gastrointestinal tract and to increase intestinal permeability leading to high bioavailability. In this review, the classification and properties as well as mechanisms of the AMPs used in infectiology are first described. Then, the different pharmaceutical forms existing in the market for oral administration are presented. Finally, the formulation technologies, including microparticle- and nanoparticle-based DDSs, used to improve the oral bioavailability of AMPs are reviewed.

The First Study Evaluating Effectiveness and Safety of the Endoscopic Sleeve Gastroplasty in HIV Patients.

The authors evaluated, retrospectively, the endoscopic sleeve gastroplasty impact in seven HIV patients, regarding effectiveness and safety outcomes. The mean baseline body mass index (BMI) was 33.76 kg/m2. The mean baseline CD4+ cell count was 690.43 cells/mm3, and the baseline viral load was undetectable. After 6 months, absolute weight loss, percentage of excess weight loss, percentage total weight loss, and BMI reduction were 20.2 ± 2.6 kg, 85.5 ± 11.1%, 21.3 ± 2.4%, and 7.1 ± 0.8 kg/m2, respectively. No patients presented severe adverse events. After 6 months, the viral load remained undetectable and the mean CD4+ cell count was 710.57 cells/mm3. The endoscopic sleeve gastroplasty is an effective and safe procedure to perform in obese HIV patients.

Corticotroph adenoma and pituitary fungal infection: a rare association.

SUMMARY: Pituitary infections, particularly with fungus, are rare disorders that usually occur in immunocompromised patients. Cushing's syndrome predisposes patients to infectious diseases due to their immunosuppression status. We report the case of a 55-year-old woman, working as a poultry farmer, who developed intense headache, palpebral ptosis, anisocoria, prostration and psychomotor agitation 9 months after initial diabetes mellitus diagnosis. Cranioencephalic CT scan showed a pituitary lesion with bleeding, suggesting pituitary apoplexy. Patient underwent transsphenoidal surgery and the neuropathologic study indicated a corticotroph adenoma with apoplexy and fungal infection. Patient had no preoperative Cushing's syndrome diagnosis. She was evaluated by a multidisciplinary team who decided not to administer anti-fungal treatment. The reported case shows a rare association between a corticotroph adenoma and a pituitary fungal infection. The possible contributing factors were hypercortisolism, uncontrolled diabetes and professional activity. Transsphenoidal surgery is advocated in these infections; however, anti-fungal therapy is still controversial. LEARNING POINTS: Pituitary infections are rare disorders caused by bacterial, viral, fungal and parasitic infections. Pituitary fungal infections usually occur in immunocompromised patients. Cushing's syndrome, as immunosuppression factor, predisposes patients to infectious diseases, including fungal infections. Diagnosis of pituitary fungal infection is often achieved during histopathological investigation. Treatment with systemic anti-fungal drugs is controversial. Endocrine evaluation is recommended at the time of initial presentation of pituitary manifestations.