Compassionate Treatment Research Articles

Metapopulation model of phage therapy of an acute Pseudomonas aeruginosa lung infection.

Phage therapy is increasingly employed as a compassionate treatment for severe infections caused by multidrug-resistant (MDR) bacteria. However, the mixed outcomes observed in larger clinical studies highlight a gap in understanding when phage therapy succeeds or fails. Previous research from our team, using in vivo experiments and single-compartment mathematical models, demonstrated the synergistic clearance of acute P. aeruginosa pneumonia by phage and neutrophils despite the emergence of phage-resistant bacteria. In fact, the lung environment is highly structured, prompting the question of whether immunophage synergy explains the curative treatment of P. aeruginosa when incorporating realistic physical connectivity. To address this, we developed a metapopulation network model mimicking the lung branching structure to assess phage therapy efficacy for MDR P. aeruginosa pneumonia. The model predicts the synergistic elimination of P. aeruginosa by phage and neutrophils but emphasizes potential challenges in spatially structured environments, suggesting that higher innate immune levels may be required for successful bacterial clearance. Model simulations reveal a spatial pattern in pathogen clearance where P. aeruginosa are cleared faster at distal nodes of the bronchial tree than in primary nodes. Interestingly, image analysis of infected mice reveals a concordant and statistically significant pattern: infection intensity clears in the bottom before the top of the lungs. The combined use of modeling and image analysis supports the application of phage therapy for acute P. aeruginosa pneumonia while emphasizing potential challenges to curative success in spatially structured in vivo environments, including impaired innate immune responses and reduced phage efficacy.

Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate.

Multimodal temporal therapy orchestrated to leverage immunotherapy, tumor-targeted chemotherapy, and natural killer (NK) cell therapy may provide an opportunity to induce immunogenic cell death for tumor response and increased survival in patients with recurrent cancer. The interleukin-15 (IL-15) superagonist N-803, an enhancer of NK cells, CD4 + T cells, cytotoxic CD8 + T cells, and memory T-cell activity, combined with off-the-shelf PD-L1-targeted high-affinity NK (PD-L1 t-haNK) cells represent novel immunotherapies designed to overcome an immunosuppressive tumor microenvironment (TME). The epidermal growth factor receptor-targeted antibody-nanocell conjugate E-EDV-D682 provides tumor-targeted chemotherapy in the form of its anthracycline metabolite PNU159682 (nemorubicin) cargo and is currently being studied in combination with immunomodulatory EDVs delivering the adjuvant α-galactosyl ceramide (GC). Here, we report the compassionate use treatment of this combination in a patient with recurrent, metastatic pancreatic cancer (mPC) after 3 lines of therapy. Under the initial single-patient Investigational New Drug (spIND) protocol, the patient received N-803, PD-L1 t-haNK cells, and the albumin doxorubicin conjugate aldoxorubicin for ~27 months. The patient's disease became stable on this regimen, and a transient complete response was observed by ~14 months of therapy. Due to progression, a second spIND protocol was designed whereby the patient received E-EDV-D682 plus EDV-GC for more than 24 months, which resulted in stable disease and the patient's continued survival at the time this report was written. The patient's extended survival despite the dire prognosis associated with recurrent mPC points to the merits of this temporal combination regimen in overcoming immuno-chemo resistance with enhanced immune activity required for tumor response and extended survival.

Case Study On the Landmark Ruling On Jallikattu- A Critical Analysis Contemplating the Deviation from Ecocentric Approach

The case "Animal Welfare Board of India vs. A. Nagaraja & Ors," which was determined on May 7, 2014 and Animal Welfare Board of India & Ors vs Union Of India & Anr decided on May 18, 2023, dealt with the practice of Jallikattu. Jallikattu is a traditional event in Tamil Nadu and Maharashtra that involves bulls. This activity, in which individuals attempt to seize money fastened to the horns of a bull, has developed into a pastime that inflicts considerable suffering and injury to the animals. The Supreme Court of India determined that the utilization of bulls in activities such as Jallikattu and bullock cart racing amounted to cruelty, therefore infringing upon the animals' entitlements under Article 21 of the Indian Constitution, which ensures the right to life and freedom. The court's ruling underscored the need of ethical treatment of animals, in accordance with current perspectives on animal welfare. The verdict aimed to prohibit these activities in order to prevent the physical and psychological torment of bulls utilized for human amusement during cultural festivities. This ruling represented a noteworthy advancement in acknowledging and safeguarding animal rights in India, but also considering the need to prevent animal abuse and ensure public safety, while taking into account traditional customs. The case exemplified the convergence of law, culture, and animal ethics, establishing a precedent for the compassionate treatment of animals within the legal framework of the country.

(116) SUBJECTIVE AND GENITAL SEXUAL RESPONSE IN FEMALE BREAST CANCER SURVIVORS: RESULTS FROM A PSYCHOPHYSIOLOGY STUDY

Abstract Introduction Sexual dysfunction is a prevalent concern affecting more than 70% of female breast cancer survivors, casting a substantial shadow on their quality of life. Beyond the physical impact of cancer and its treatments, the emotional and psychological toll of sexual dysfunction introduces additional challenges, amplifying stress levels and undermining overall well-being. Acknowledging the profound implications of sexual dysfunction in this group and the absence of therapies, there is an urgent need to delve deeper into the intricacies of its manifestations. Objective This study aimed to gather preliminary data on psychophysiological aspects of sexual function in premenopausal breast cancer patients undergoing antihormonal therapy and compare them with a healthy control group. Exploring sexual arousal in breast cancer patients may unveil potential targets for innovative treatment strategies to address sexual dysfunction in this population. Methods Participants were prescreened during a telephone interview. We included 40 premenopausal breast cancer survivors with an age range of 29 to 57 years (M = 43.5, SD = 6.36) on current hormonal treatment and 20 healthy controls with an age range of 22 to 35 (M = 27.55, SD = 3.19). Physiological measures (VPA and HRV), subjective sexual arousal (SSA) and self-reported orgasm were assessed in response to audiovisual stimuli and vibrotactile clitoral stimulation sexual stimuli in breast cancer survivors and healthy controls. Self-reported measures like the Female Sexual Function Index (FSFI), the Sexual Self-Esteem Inventory (SSEI) und the PROMIS29 were incorporated. Data were analyzed using 2-level mixed effect models. Results No significant differences in VPA scores were observed between healthy controls and breast cancer survivors. Both groups exhibited a greater genital response to clitoral vibrator use than to visual stimuli. Group differences emerged in SSA and HRV, with higher SSA and lower HRV being detected. Breast cancer survivors climaxed less frequently than healthy controls and had significantly lower self-reported sexual function. Conclusions Physiological measures of arousal in breast cancer survivors were comparable to healthy controls and only subjective arousal differed. This finding indicates that subjective arousal should be further explored as the focus of intervention and treatment methods for breast cancer patients experiencing sexual dysfunction. Our findings underscore the importance of tailored strategies that resonate with individual narratives, acknowledging the emotional intricacies of post-cancer sexual well-being. This study not only contributes to scientific knowledge but also calls for a compassionate and personalized treatment paradigm, enriching the landscape of survivorship care. Disclosure Yes, this is sponsored by industry/sponsor: WOW Tech GmbH Clarification: No industry support in study design or execution.

Effect of sodium thiosulfate anhydrous on cisplatin-induced ototoxicity in pediatric cancers: Turkish compassionate use treatment protocol—Updated results.

e15075 Background: Cisplatin induced ototoxicity (CIO), with permanent hearing loss is observed in >60% pediatric patients in Turkey. PEDMARK (Sodium Thiosulfate anhydrous) reduced the risk of CIO cases with non-metastatic solid tumors observed in Phase 3 studies (SIOPEL 6 & COG ACCL0431). We aimed to evaluate the investigational product PEDMARK provided for pediatric cases via a National Compassionate Use Treatment Protocol (CUP) in Turkey. Methods: Patients (1 month to <18 years) with a localized, nonmetastatic solid tumor, standard-risk hepatoblastoma (HBB), nasopharyngeal carcinoma (NPC) and medulloblastoma MB whose treatment plans were including cisplatin were eligible. PEDMARK was administered intravenously 6 hours after each cisplatin dose infusion. Adverse events, demography, pre and post- hearing were recorded from 21OCT2019-21SEPT2022. Results: The CUP enrolled 12 patients, 8 HBB, 3 NPC and 1 MB in 3 years, from 6 academic institutions. HBB patients' median age was 1year (3mos-3 yrs). All pts had newly diagnosed HBB PRETEXT 3 (n = 5) with a median baseline AFP OF 54.000. 3 NPC age 13-17 yrs, MB 6yrs of age. All patients had Brock Grade 0 on hearing tests prior to treatment Patients received a median 0f 6 cycles (range 4-6) of cisplatin and PEDMARK. Patients with hearing tests available post-treatment (n=11), all maintained Brock Grade 0. At a median of 0.8mos post-treatment, CR were observed in all patients except one HBB with progressive disease. All CRs wer sustained 18.8 mos. AEs in 2 patients were Grade 1-2 nausea/vomiting, no Grade >3 AEs were reported. Conclusions: PEDMARK was well tolerated, provided via a Turkish CUP to reduce the CIO in pediatric patients with nonmetastatic solid tumors. No hearing loss was observed/ detected post-treatment and the tumor outcomes were consistent with the Phase 3 studies. This is very encouraging.

The community health worker experience and perception toward mental illness: A multi-settings cross-sectional study in Indonesia.

The experiences and perceptions of Community Health Workers toward mental illness are vital for tailoring interventions, reducing stigma, improving access to services, and fostering community engagement in mental health initiatives. This study investigates the experiences of community health worker and their perception of mental illness. A multi-settings cross-sectional study was conducted among 487 Community Health Workers. Their experience and perception toward mental illness were studied with questionnaires, which examined their general perception, religious-related perception, cause, treatment, and expectation for mental treatment. Most participants concurred that serving as a community health worker enhances their communication abilities (90.4%), strengthens connections with community health center staff (84.8%), boosts self-confidence (84.6%), and refines their capacity to identify signs of mental disorders (77%). Most notably, they consider their fellow community health workers essential to their extended family. Furthermore, a notable proportion associates' mental illness with religious elements, with 19.5% believing it can result from a lack of religious worship and a minority attributing it to witchcraft or black magic (3.5%). In terms of treatment, 14.2% think Ruqyah can cure mental illness, 6.4% believe in treatment by religious scholars, and a similar percentage (6.4%) think no medication or treatment is necessary for mental problems. Participants overwhelmingly recognize the positive impact of serving as community health workers, citing improvements in communication, relationships with health center staff, self-confidence, and mental disorder identification. The strong bond among community health workers, likened to an extended family, emphasizes their collective importance. Additionally, the majority advocates for compassionate treatment of individuals with mental illness. These findings underscore the complex interplay of professional, communal, and cultural elements in addressing community mental health.

Virtue Ethics as Animal Ethics in Philosophy of the Islamic World

Abstract Virtue ethics may seem to be a less useful paradigm for ethical thinking than utilitarianism and deontology, insofar as it seems rather vacuous to be told to act as a virtuous person would act. But the topic considered here shows that this need not be true. Since virtue ethicists (and virtuous persons, according to this ethical approach) value the features that make human lives (more) excellent, they also value the features that make other lives (more) excellent, by way of the virtues of mercy, generosity, and justice. And this is true whether or not the lives in question are human or animal. To put it another way, a good agent will be one who shows goodness towards beings who are capable of having good lives. While that phrasing again sounds close to tautologous, it becomes substantive when we spell out which beings have such a capacity, and in what ways things can go well or badly for them. Virtue ethicists from the Islamic world were especially well placed to do that, since they also inherited from Aristotle (d. 322 BCE) a teleological conception of nature. In light of this, it comes to seem almost inevitable that philosophers in this tradition would endorse compassionate treatment of animals. In cases where they fail to do so, the failure is bound up with a tendency to downgrade the value of practical virtue as a whole. Rigorously intellectualist ascetics are unlikely to show much interest in the welfare of animals, being disinterested even in their own animal souls.

Rapid Bench to Bedside Therapeutic Bacteriophage Production.

It has been over 100years since bacteriophages (phages) were used as a human therapeutic. Since then, phage production has dramatically evolved. Current phage preparations have fewer adverse effects due to their low bacterial toxin content. As a result, therapeutic phages have become a predominant class of new antimicrobials and are being widely used for compassionate treatment of multidrug-resistant (MDR) infections. We describe herein a protocol for the production and ultrapurification of phages. By this technique, it is possible for a lab experienced with the process to produce >109 plaque-forming units (PFU) per mL of Gram-negative phages that meet FDA endotoxins limits for intravenous infusions in as little as 48hours. We provide illustrations of the process and tips on how to safely remove bacterial toxins from phage lysates. Although dependent on the phage strain, the approach described can rapidly generate and purify phages for a variety of applications.

FRI069 Treatment With Mibavademab, A Novel Leptin Receptor Agonist, Is Associated With Improvement In Weight And Associated Comorbidities In Congenital Leptin Deficiency

Abstract Disclosure: E. Ozsu: None. L. Akin: None. M. Aydin: None. M. Berberoglu: None. D. Stein: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. O. Pagovich: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. B. Olenchock: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. S. Podgrabinska: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. C.A. Harris: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. J. Mendell: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. R. SinhaRoy: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. J. Altarejos: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. B. Akinci: Advisory Board Member; Self; Amryt Pharmaceuticals, Regeneron, Third Rock Ventures. Consulting Fee; Self; Third Rock ventures, Regeneron, Amryt Pharmaceuticals. Speaker; Self; Astra Zeneca, Lilly, MSD, Novartis, Novo Nordisk, Sanofi Aventis. E.A. Oral: Advisory Board Member; Self; Third Rock Ventures, Regeneron, Rejuveneate Bio. Consulting Fee; Self; Amryt Pharmaceuticals, Regeneron. Grant Recipient; Self; Regeneron, Novo Nordisk, GI Dynamics, Ionis Pharmaceuticals, Fractyl, Rhythm Pharmaceuticals. Other; Self; Amryt Pharmaceuticals. Background: Congenital leptin deficiency (CLD) is a form of extreme obesity caused by biallelic pathogenic variants in the leptin gene. Recombinant human leptin normalizes weight and neuroendocrine/metabolic abnormalities in CLD, however, daily dosing is required with a risk of immunogenicity. Mibavademab is an investigational human leptin receptor agonist monoclonal antibody. Case report: A Turkish male infant came to medical attention due to rapid weight gain at 2 months of age and work-up led to identification of homozygous variant in the leptin gene causing CLD. He was treated with Metreleptin for 11 months starting at age 2. When weight regain despite Metreleptin therapy was noted, neutralizing antibody (Nab) was found to be strongly positive. He continued to gain weight rapidly causing impaired mobility, and required nightly oxygen with BIPAP. He was hospitalized frequently with upper respiratory tract infections and needed ICU care four times during the 5th year of his life. At age 5 years and 9 months and body weight of 89.9 kg (BMI SD:5.7), the compassionate use application to use Mibavademab was approved by the local ethics board and the Ministry of Health. The patient received an intravenous loading dose of Mibavademab followed by weekly subcutaneous (SC) administration of Mibavademab. SC dose and diet intake were carefully adjusted based on drug levels, and intended vs. observed weight loss. Results: Weight reduction was first observed in the first week of treatment, which was rapid with an average velocity of 7.1 kg/month until month 7. Upon dose adjustment, velocity decreased to 3.1 kg/month. Weight stabilization was achieved at month 11 at a weight of 28.9 kg (BMI SD:1.0) while using Mibavademab every two weeks. Overall, drug levels were significantly higher than projected in the first 28 weeks and then brought to predicted stable levels upon dose adjustments. Despite the rapid weight loss, improved mobility and age-appropriate growth were observed. There were no signs of precocious puberty. Glucose tolerance, insulinemia, and liver parameters all improved favorably over treatment period and there were no safety signals. The patient discontinued BIPAP treatment and sleep assumed a normal pattern without hypoxia. Conclusions: Compassionate treatment with Mibavademab for up to 60 weeks was associated with improvements in body weight and metabolic parameters, and was well-tolerated in a young child with CLD and Nab against metreleptin. Substantial benefits in mobility, social engagement, and respiratory status were also noted without adverse events. Mibavademab represents a potential new therapeutic option for patients with CLD and this first experience will provide guidance for treatment of similar patients. Presentation: Friday, June 16, 2023

Molecular Mechanisms Involved in the Chemical Instability of ONC201 and Methods to Counter Its Degradation in Solution.

Glioblastoma is one of the most common and aggressive forms of brain tumor, a rare disease for which there is a great need for innovative therapies. ONC201, a new drug substance, has been used in a compassionate treatment program where the choice of dosage form and regimen have yet to be justified. The prior knowledge needed to anticipate ONC201 stability problems has recently been partially addressed, by (i) showing that ONC201 is sensitive to light and oxidation and (ii) identifying the molecular structures of the main degradation products formed. The aim of the work presented here was to improve our understanding of the degradation pathways of ONC201 using data from ab initio calculations and experimental work to supplement the structural information we already published. The C-H bonds located αto the amine of the tetrahydropyridine group and those located alpha to the imine function of the dihydroimidazole group exhibit the lowest bond dissociation energies (BDEs) within the ONC201 molecule. Moreover, these values drop well below 90 kcal.mol-1 when ONC201 is in an excited state (S1; T1). The structures of the photoproducts we had previously identified are consistent with these data, showing that they would have resulted from radical processes following the abstraction of alpha hydrogens. Concerning ONC201's sensitivity to oxidation, the structures of the oxidation products matched the critical points revealed through mapped electrostatic potential (MEP) and average local ionization energy (ALIE). The data obtained from ab initio calculations and experimental work showed that the reactivity of ONC201 to light and oxidation conditions is highly dependent on pH. While an acidic environment (pH < 6) contributes to making ONC201 quantitatively more stable in solution in the face of oxidation and photo-oxidation, it nevertheless seems that certain chemical groups in the molecule are more exposed to nucleophilic attacks, which explains the variation observed in the profile of degradation products formed in the presence of certain antioxidants tested. This information is crucial to better understand the stability results in the presence of antioxidant agents and to determine the right conditions for them to act.

From industrialised to mindful medicine: including the politics of need and trust in child psychiatry

SUMMARYDiagnostic systems are not conducive to compassionate health-bringing psychiatric treatment. The systems were built around the fallacy that the politics of biomedicine could be reliably applied to the emergent properties of human psychological suffering and enable diagnosis-specific treatment packages. The resulting industrialised medicine, which reified people, failed to facilitate the compassion needed for healing. This article outlines an approach to psychiatric practice that involves understanding children's suffering and vulnerabilities in terms of their attachment strategies and adaptation to their context and takes a mindful approach to developing compassionate collaborative treatment goals (intelligent kindness). A shift towards mindful psychiatric medicine would encourage politicians to serve the people by addressing the contexts associated with human suffering and what makes people vulnerable, especially social inequalities. Healthy societies in which the psychiatric dis-ease of the population is adequately addressed will not be built with limited biomedical understanding of dis-ease.

Wealth of Knowledge and Passion: Patient Perspectives on Vaginal Estrogen as Expressed on Reddit

To qualitatively analyze the knowledge, attitudes, and beliefs of women regarding genitourinary syndrome of menopause (GSM) and vaginal estrogen therapy as expressed on Reddit, a public, anonymous internet forum for discussion and information sharing. "r/menopause," a Subreddit with >30,000 subscribers, was queried for "vaginal estrogen" to collect postings related to vaginal estrogen in October 2022. Posts were analyzed qualitatively by 2 independent researchers. The principles of grounded theory were applied, and preliminary themes were generated. These themes were used to derive emergent concepts. Sixty-seven unique posts with 1101 responses were analyzed. Qualitative analysis revealed 5 preliminary themes: (1) questions regarding medication usage, (2) medication side effects, (3) medication alternatives, (4) frustration with the medical system, and (5) seeking validation for symptoms and experiences. Three emergent concepts were derived: (1) women experience bothersome side effects from menopause, and they desire compassionate and effective medical treatment; (2) women are engaged and active participants in their health and health care decisions; and (3) women perceive that their concerns are not taken seriously and seek validation for their medical conditions. Peri- and post-menopausal women have many questions and concerns about the condition of GSM and vaginal estrogen as treatment. They also have a broad range of frustrations including access to health care and questions about the usage of vaginal estrogen. By better understanding patient perspectives, physicians can better meet women's needs and improve care for GSM.

Navigating Early Alzheimer's Diagnosis: A Comprehensive Review of Diagnostic Innovations.

The hunt for early Alzheimer's disease detection has created cutting-edge diagnostic instruments with enormous promise. This article examines the many facets of these developments, focusing on how they have revolutionised diagnosis and patient outcomes. These tools make it possible to detect tiny brain changes even before they give birth to clinical symptoms by combining cutting-edge biomarkers, neuroimaging methods, and machine-learning algorithms. A significant opportunity for therapies that can slow the course of the disease exists during this early detection stage. Additionally, these cutting-edge techniques improve diagnostic precision, objectivity, and accessibility. Liquid biopsies and blood-based biomarkers provide non-invasive alternatives, filling accessibility gaps in diagnosis. While issues with standardisation, ethics, and data integration continue, collaboration within research, clinical practice, and policy realms fuels positive developments. As technology advances, the way towards better Alzheimer's diagnosis becomes more evident, giving patients and families dealing with this difficult illness fresh hope. The synergy between scientific advancement and compassionate treatment is crucial for improving Alzheimer's disease diagnosis, as this paper emphasises.

Use of Multiple Doses of Intravenous Infusion of Umbilical Cord-Mesenchymal Stem Cells for the Treatment of Adult Patients with Severe COVID-19-Related Acute Respiratory Distress Syndrome: Literature Review.

Acute respiratory distress syndrome (ARDS) is a critical complication in severe COVID-19 patients. The intravenous infusion (IVF) of umbilical cord- (UC-) mesenchymal stem cells (MSCs), validated to substantially reduce the release of several inflammatory cytokines in vivo, was also shown to exhibit benefits in improving hypoxemia among severe COVID-19 patients. A single dose of IVF-UC-MSCs therapy for severe COVID-19 patients was shown to alleviate the initial ARDS severity, but have 50%-67% case-fatality rates. In Taiwan, few adult patients with severe COVID-19-induced ARDS receiving compassionate adjuvant treatment consisting of either a single dose (1-10 × 106 cells/kg body weight (kg BW)) or three doses (5 × 106 cells/kg BW in each dose) of IVF-UC-MSCs had good outcomes. However, the optimal dosage and rounds of IVF-UC-MSCs administration for the treatment of severe COVID-19 patients with ARDS are undetermined. We reviewed the 2020-2022 PubMed literature database concerning the clinical efficacy of IVF-UC-MSCs among severe COVID-19 patients. The data of COVID-19 case series in the PubMed literature revealed a notable heterogeneity in the therapeutic dosage (a single dose: 1-10 × 106 cells/kg BW; and three doses: 50-200 × 106 cells/kg BW in each dose) and the post-ARDS days of IVF-UC-MSCs administration (a single dose: 1-12; and multiple doses: 5-14) for the treatment of severe COVID-19-associated ARDS. The survival rates among these severe COVID-19 patients ranged from 50% to 76%. However, an overall rate of 93.1% of significant improvement in hypoxemia was observed for the COVID-19 survivors receiving IVF-UC-MSCs at the initial ARDS stage. According to our analysis, the ideal treatment dosage of IVF-UC-MSCs for severe COVID-19-induced ARDS is likely 5 × 106 cells/kg BW for three cycles within 5 days of ARDS onset in severe COVID-19 patients.

Summary of the conference "Phages and phage therapy: from Félix d'Hérelle to 2.0 phages"

As part of the 25th edition of the Francophone Virology Days, Pr. Frédéric Laurent held the conference "Phages and phage therapy: from Félix d'Hérelle to 2.0 phages". Frédéric Laurent detailed the history of phages: from their discovery and their first use in early 1920s, through their abandonment in Western world in the 1940s in favor of antibiotics, then their reappearance in recent years within the context of the emergence of multi-resistant bacterial strains. Throughout this presentation, Pr.Laurent also detailed general functioning of phages, their chain of bioproduction and quality control, the progress to be made in the compassionate treatment of patients in therapeutic failures.

Safety and Efficacy of Ceftaroline in Neonates With Staphylococcal Late-onset Sepsis: A Case Series Analysis.

Treatment of late-onset neonatal staphylococcal sepsis is sometimes challenging with feared side effects of vancomycin, increasing minimal inhibitory concentrations and questions about catheter management. In case of failure, ceftaroline was administered as a compassionate treatment in 16 infants (gestational age of less than 32 weeks and less than 28 postnatal days), whose first-line treatment failed. We report 11 successes and no severe adverse drug reactions. Larger data are required to confirm these encouraging results.

Socio-Psychological Challenges of Women Having Polycystic Ovary Syndrome (PCOS)

PCOS can have a substantial socio-psychological influence on women's lives, along with its clinical symptoms.This qualitative phenomenological investigation observed the emotions, body image, societal stigma, interactions, and coping techniques of women with PCOS. In-depth interviews with a varied group of women highlighted several major themes, including the difficult emotional journey, challenges with a perception of oneself and body image, loneliness or ostracism, and the value of support and connection networks. The study's findings have crucial consequences for healthcare practitioners, politicians, and people with PCOS. Understanding the particular issues that these women encounter allows healthcare practitioners to deliver more comprehensive and compassionate treatment. Policymakers may also create legislation to benefit women experiencing PCOS and decrease the prejudice associated with the disorder.Lastly, women with PCOS may utilize the study's findings in order to comprehend their own circumstances and develop solutions to manage the difficulties they confront.

Held back by limited experience, training, and therapeutic confidence: self-perceptions of Czech mental health professionals about addressing paraphilic-related concerns

A body of literature shows that a considerable proportion of mental health and social work professionals who are approached by help-seeking people with paraphilic interests find themselves unprepared to respond to these individuals adequately. In the Czech Republic, the professionals’ self-perceptions about addressing various paraphilic-related themes and concerns remain largely unexplored. The objective of the present study was to fill this knowledge gap by conducting an anonymous online survey among mental health and social work practitioners expected to have professional experience with help-seeking people presenting with paraphilic interests and related themes. The focus of the study was on two broad areas of paraphilic interest: attraction to minors and sexual non-consent and violence against adults. The survey results in 61 practitioners suggested limited self-perceived capacity to address paraphilic-related interests and concerns, which involved navigating relationships with significant others, mitigating anxiety and depression, and enhancing intimate functioning, rather than handling paraphilic interests per se. Insufficient paraphilic-related professional experience and training were named among the major self-perceived obstacles to efficient help provision. Through identification of current gaps in professionals’ engagement with this stigmatized, hard-to-reach, at-risk population we hope to foster the development of competent, client-oriented, and compassionate counselling and treatment services in the Czech Republic.

Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy.

The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined with different chemotherapy regimens is being investigated in various clinical settings. We conducted a retrospective clinical chart review of 25 patients with relapsed/refractory neuroblastoma who had failed ≥1 second-line therapy and received compassionate use treatment with dinutuximab beta long-term infusion combined with the induction chemotherapy regimens N5 (cisplatin, etoposide, vindesine) and N6 (vincristine, dacarbazine, ifosfamide, doxorubicin) recommended by the German Pediatric Oncology and Hematology Group [GPOH] guidelines. The treatment did not result in any unexpected severe toxicities or in any major treatment delays. Grade 3/4 pain was reported by 4/25 patients in cycle 1, decreasing to 0/9 patients in cycles 3 and 4. The median follow-up was 0.6 years. The best response in this group was 48% (12/25 patients), which included three patients with minor responses. At 1 year, the estimated event-free survival was 27% (95% confidence interval [CI] 8-47) and overall survival was 44% (95% CI 24-65). Combining long-term infusion of dinutuximab beta with N5 and N6 chemotherapy demonstrated an acceptable safety profile and encouraging objective response rates in heavily pretreated patients with high-risk neuroblastoma, warranting further evaluation in clinical trials.

Hunting Tourism in Mexico from the Perspective of Philosophical Posthumanism

Abstract Historically, humanism has relied on the idea that human beings enjoy a superior ontological position to other beings. This has legitimized the exploitation and killing of nonhuman animals, regarded as means to attain human ends, as instruments or resources for human use and benefit—environmental, social, economic, or recreational. With the emergence of philosophical posthumanism in its association with anti-speciesism—which ontologically places humans and other animals in an equal position as sentient beings—the dominant discourses that try to justify hunting tourism in Mexico lose their ethical standpoint, as do the speciesist and anthropocentric arguments for the commodification of nonhuman animals for recreational purposes. Exploring the interconnections among animal exploitation, philosophical posthumanism, anti-speciesism, and hunting tourism allows delving into the ethical implications of these practices, looking for alternative perspectives, and advocating a more compassionate and respectful treatment of nonhuman beings.