Viola Neudecker1#, Jose F. Perez-Zoghbi1# and Ansgar M. Brambrink1*

Department of Anesthesiology, Columbia University Medical Center, New York, NY 10032, USA.;

The concern about anesthesia-induced developmental neurotoxicity (AIDN) in infants and young children arises from animal studies indicating potential long-term neurobehavioral impairments following early-in-life anesthesia exposure. While initial clinical studies provided ambiguous results, recent prospective assessments in children indicate associations between early-in-life anesthesia exposure and later behavioral alterations. Ethical constraints and confounding factors in clinical studies pose challenges in establishing a direct causal link and in investigating its mechanisms. This commentary on a recent study in non-human primates (NHPs) focuses on exploring the role of neuroinflammation and alterations in brain functional connectivity in the behavioral impairments following early-in-life anesthesia exposure. In juvenile NHPs, chronic astrogliosis in the amygdala correlates with alterations in functional connectivity between this area with other regions of the brain and with the behavioral impairments, suggesting a potential mechanism for AIDN. Despite acknowledging the study's limitations, these findings emphasize the need for further research with larger cohorts to confirm these associations and to establish a causal link between the neuroinflammation and the behavioral alterations associated with early-in-life anesthesia exposure.

DOI: 10.29245/2578-3009/2024/2.1255 View / Download Pdf

Tiaman Diarra1, Joseph Okeibunor2*, Bailo Diallo2, Nkechi Onyeneho3, Barry Rodrigue2, Michel N’da Konan Yao2, Zabulon Yoti2, Soce Fall2

1Independent Consultant, Mali

2World Health Organization, Switzerland

3University of Nigeria, Nsukka

While treating a disease, patients or their relatives make decisions to pursue different therapeutic options, and various stages are involved in searching for a cure. This paper explored the pattern of health-seeking in the Democratic Republic of Congo (DRC) during the 10th Ebola virus disease (EVD) outbreak. Eight hundred randomly selected adults were surveyed using a questionnaire. Qualitative data were also collected through in-depth interviews with 17 community leaders and 20 focus group discussions with community members. The results showed that modern healthcare facilities are not usually considered the first option for treatment. The therapeutic journey generally begins with the patients, who treat themselves based on the information they know about the disease and the resources they have at their disposal. However, if the disease is not cured through self-medication, then patients or their relatives will visit a pharmacy. Patients request medication they know to be effective in treating the disease, and relatives can also assist in obtaining medication in the case of immobile patients. Pharmacies commonly sell the medication to patients or their relatives without a medical prescription.

DOI: 10.29245/2578-3009/2023/S3.1101 View / Download Pdf

Tiaman Diarra1, Joseph Okeibunor2*, Bailo Diallo2, Nkechi Onyeneho3, Barry Rodrigue2, Michel N’da Konan Yao2, Zabulon Yoti2, Mamoudou Harouna Djingarey4, Soce Fall2, Abdou Salam Gueye2

1Independent Consultant, Mali

2World Health Organization, Switzerland

3University of Nigeria, Nsukka

This paper examines the impact of insecurity on the management of the Ebola virus disease epidemic in the Democratic Republic of the Congo provinces of North Kivu and Ituri. In these provinces, insecurity has been one of the biggest obstacles in the response to the Ebola outbreak. When the epidemic began, these provinces were already insecure—creating unfavorable circumstances for implementing epidemic response activities. While the ninth epidemic in the Equateur province was brought under control in record time, the same was not true for the tenth epidemic in North Kivu and Ituri. Since the epidemic began, teams were organized to address all aspects of the response. These response teams conducted extensive fieldwork, including epidemiological surveillance, risk communication and community involvement, infection prevention and control, vaccination, dignified and safe burials, care at transit centers and Ebola treatment centers, and medical and psychosocial care for the recovered. They faced confrontational reactions from the communities, which jeopardized their security. The insecure state of the provinces led to the destruction and damage of infrastructure, including healthcare facilities, which affected the ability of rescue teams to access people needing care as well as the resources they needed to care for the ill. Worse yet, the insecurity took other forms, including threatening and kidnapping members of the response teams, lodging protests against the response activities in towns or health zones, committing violence against teams responsible for safe and dignified burials, instigating altercations between community members and members of the response team, and encouraging general resistance by the population. This level of insecurity interrupted or even halted response activities in some areas—sometimes for more than two weeks, decreasing the efficiency of the response teams, particularly in monitoring contacts due to the inability to access certain communities. Additionally, certain acts of protest, such as community members handling bodies as a demonstration of their opposition to safe and dignified burials, likely intensified disease spread. However, the involvement of community leaders, at least, made dialogue and negotiation possible between the response teams and community members, as such efforts led to communities contributing to the security of personnel involved in the fight against the Ebola epidemic in North Kivu and Ituri provinces.

DOI: 10.29245/2578-3009/2023/S3.1102 View / Download Pdf

Nkechi G. Onyeneho1*, Ngozi Idemili Aronu1, Ijeoma Igwe1, Joseph Okeibunor2, Tieman Diarra3, Julienne Ngoudougou Anoko2, Mamoudou Harouna Djingarey4, Zabulon Yoti2, Dick Chamla, Abdou Salam Gueye

1University of Nigeria, Nsukka

2World Health Organization, Switzerland

3Independent Consultant, Mali

4Independent Public Health Expert, Niger

Although an outbreak of the Ebola virus disease affects an entire population, women are more susceptible to the virus than men. Throughout the outbreaks of the Ebola virus disease in Central and West Africa, women have been impacted more significantly. Generally, over half of those who become ill are women. The situation is the same in terms of mortality. Further, the outcomes of the epidemic negatively affect women socially, as many become the heads of households following the loss of their spouses, which burdens them with new responsibilities. Women’s access to health services is also lowered, as the epidemic usually leads to fewer healthcare workers, impacting gynecological assistance. Consequently, women are more exposed to health problems, particularly during pregnancy. Several factors contribute to the greater exposure of women to the Ebola virus disease during an epidemic. First, female healthcare workers are at the frontline of the fight against the virus. Second, women’s duties in the domestic context increase their exposure to contamination, as they look after children and care for sick household members. Finally, women are responsible for several community duties such as public tasks and rituals. In the case of rituals, women undertake tasks such as undressing, washing, and dressing the deceased. Likewise, they engage in agricultural work and grocery shopping locally, as well as at cross-border markets. They also manage domestic chores such as fetching water in public places. Additionally, women have less access to information on the disease and its prevention and are thus more vulnerable. However, women’s vulnerability is less visible, since information on the epidemic and response is not gender specific. This is true for the number of suspected cases, confirmed cases, vaccinated people, alerts, contacts, contacts followed up, and screened travelers. It is therefore crucial to highlight the importance of gender in the response to the Ebola virus disease epidemic, as women are the primary victims.

DOI: 10.29245/2578-3009/2023/S3.1103 View / Download Pdf

Nkechi G. Onyeneho1*, Ngozi Idemili Aronu1, Ijeoma Igwe1, Joseph Okeibunor2, Tieman Diarra3, Bailo Diallo2, Bairo Hamadou2, Barry Rodrigue2, Mamoudou Harouna Djingarey4, Zabulon Yoti2, Michel N’da Konan Yao2, Soce Fall2, Dick Chamla2, Abdou Salam Gueye2

1University of Nigeria, Nsukka

2World Health Organization, Switzerland

3Independent Consultant, Mali

4Independent Public Health Expert, Niger

Denial and rumors are two major obstacles impairing the implementation of activities in response to the Ebola virus disease (EVD) epidemic. This study investigated the roles of denial and rumors, among other challenges, in complicating the response to the EVD outbreak in the North Kivu and Ituri provinces of the Democratic Republic of the Congo. A total of 800 randomly selected respondents were surveyed using a structured questionnaire. In-depth interviews were conducted with 17 community religious and opinion leaders, as well as Ebola survivors. Furthermore, 20 focus group discussions were conducted with adult and youth male and female participants, and health care workers. The results revealed that the existence of the disease is widely denied by many, including political leaders, village chiefs, neighborhood chiefs, street chiefs, avenue chiefs, and members of the general population. These individuals generally consider the EVD to be the result of a misbehavior or a curse; consequently, the general population, including community members, teachers, and even health care professionals, refuse to comply with the authorities’ strategies to fight the epidemic. Rumors are another obstacle in response efforts. Rumors pertaining to the denial of the existence of the EVD, as well as the epidemic, Ebola treatment centers, hospitals, vaccines, and safe and dignified burials have been identified. Rumors about the EVD and the response, spread by clerics, traditional therapists, men, and women, including healthcare professionals in focus group discussions, portrayed the EVD as an invention, as if the virus had been created. The response to the EVD has been marked by these two constraints, which have often hindered the involvement of community members in the fight against the disease.

DOI: 10.29245/2578-3009/2023/S3.1104 View / Download Pdf

Joseph Okeibunor1*, Tieman Diarra2, Nkechi Onyeneho3, Bailo Diallo1, Michel N’da Konan Yao1, Mamoudou Harouna Djingarey4, Zabulon Yoti1, Soce Fall3, Dick Chamla1, Abdou Salam Gueye1

1World Health Organization, Switzerland

2Independent Consultant, Mali

3University of Nigeria, Nsukka

4Independent Public Health Expert, Niger

We explored issues around the integration of survivors in communities and the implications of the Ebola Virus Disease (EVD) response in the Democratic Republic of Congo (DRC). We conducted a survey with 800 randomly selected respondents using a structured questionnaire. Respondents were persons aged 18 years and above. Focus group discussions (FGDs) and in-depth interviews (IDIs) were employed to obtain contextual data on the issues. Community leaders, health workers, and response pillar leads engaged in IDIs, while community members were involved in FGDs. The results revealed that the survivors suffered stigmatization and, upon return to the communities, were avoided by the community members due to fear of contamination. Some thought that the survivors should be supported in adjusting to the community, while some recommended engaging the survivors in EVD response activities.

DOI: 10.29245/2578-3009/2023/S3.1105 View / Download Pdf

Nkechi G. Onyeneho1*, Ngozi Idemili Aronu1, Ijeoma Igwe1, Joseph Okeibunor2, Tieman Diarra3, Bailo Diallo2, Bairo Hamadou2, Barry Rodrigue2, Mamoudou Harouna Djingarey4, Zabulon Yoti2, Michel N’da Konan Yao2, Soce Fall2

1University of Nigeria, Nsukka

2World Health Organization, Switzerland

3Independent Consultant, Mali

4Independent Public Health Expert, Niger

Treatment centers (TCs) are the only locations designed to care for people with Ebola virus disease (EVD) symptoms. These people and their families are held at a TC as soon as they arrive at an Ebola treatment center (ETC); however, some people escape from TCs. This paper explored alternative care platforms for symptomatic people in the fight against the EVD outbreak in the Democratic Republic of Congo. Eight hundred randomly selected adults aged 18 years and above were surveyed with a uniform set of structured questionnaires. In-depth interviews were conducted with 20 community/opinion leaders, while focus group discussions were held with community members who were not involved in the questionnaire study. Our findings demonstrated that people who were suspected of having EVD preferred to be treated discreetly and at home, and were more willing to be tested at home than at a TC. People were afraid of being stigmatized if the TC exposed their admittance to the general public. This article proposes an alternative to the TCs. We suggest a temporary containment facility within the community, such as a room in the suspected person’s home. However, this requires negotiation between the response team and community members, with the latter having a significant responsibility in caring for their symptomatic relatives. The place or room for domestic temporary isolation should be chosen discreetly and placed far from the view of others. Community members will, thus, bear more responsibility for what happens while the patient is in isolation. The temporary containment area will assist in decentralizing the treatment of those with EVD symptoms. Its implementation will contribute to greater accountability of community members in the fight against EVD.

DOI: 10.29245/2578-3009/2023/S3.1106 View / Download Pdf

Nkechi G. Onyeneho1*, Ngozi Idemili Aronu1, Ijeoma Igwe1, Joseph Okeibunor2, Tieman Diarra3, Julienne Ngoudougou Anoko2, Mamoudou Harouna Djingarey4, Zabulon Yoti2

1University of Nigeria, Nsukka

2World Health Organization

3Independent Consultant, Mali

4Independent Public Health Expert, Niger

Traditional healers co-exist with orthodox medicine, especially in cases with perceived supernatural causes and during outbreaks of infectious diseases like the Ebola virus disease (EVD) in the North Kivu and Ituri provinces in the Democratic Republic of the Congo (DRC). In this study, we examined the role and potential of involving traditional healers in the national response to the Ebola virus disease outbreak in the DRC. Seventeen community leaders and 20 traditional healers were interviewed. The traditional healers managed symptoms with herbs and were not inclined to refer cases to orthodox healthcare facilities because of their confidence in their ability to handle cases with supernatural causes. The community leaders attested to the acceptance of the traditional healers in the communities, which they attributed to the efficacy of traditional healing, its uncomplicated treatment process, cause of the prolonged cough, as well as cost and the need for secrecy. Traditional healers can be educated to promptly refer cases to Ebola treatment centers for timely diagnosis and appropriate treatment.

DOI: 10.29245/2578-3009/2023/S3.1108 View / Download Pdf

Tiaman Diarra1, Joseph Okeibunor2, Bailo Diallo2, Nkechi Onyeneho3, Barry Rodrigue2, Michel N’da Konan Yao2, Zabulon Yoti2, Soce Fall2

1Independent Consultant, Mali

2World Health Organization

3University of Nigeria, Nsukka

We reviewed the involvement of civil society organizations as well as other community level organizations and structures in the response to the Ebola Virus Disease (EVD) outbreak in the Democratic Republic of Congo. A total of 800 randomly selected adults were surveyed using a uniform set of structured questionnaires. An in-depth interview guide was employed to collect information from community members and religious leaders, while focus group discussions were held with community members. The results revealed some involvement of the different organizations in the communities in the response to the EVD outbreak. However, several challenges were encountered, namely security issues, poor awareness, and non-compliance to safety measures. The findings underscore that despite considerable experience over a long period with outbreaks in the DRC, people still need to be educated about the disease.

DOI: 10.29245/2578-3009/2023/S3.1109 View / Download Pdf

Tiaman Diarra1, Joseph Okeibunor2, Bailo Diallo2, Nkechi Onyeneho3, Bairo Hamadou2, Michel N’da Konan Yao2, Zabulon Yoti2, Soce Fall2

1Independent Consultant, Mali

2World Health Organization

3University of Nigeria, Nsukka

We investigated the involvement of community members in response to the Ebola Virus Disease (EVD) epidemic in the North Kivu and Ituri provinces of the Democratic Republic of Congo. This cross-sectional study, conducted using mixed methods of data collection, included a uniformly structured questionnaire survey, which was administered to 800 randomly selected adults (aged ≥ 18 years). Further, we used qualitative tools of inquiry—focus group discussions (FGD) and in-depth interviews (IDI)—to guide the context of the information collected in the survey. Community leaders, religious leaders, and Ebola survivors were interviewed using the IDI guide, while young men (≤ 30 years), young women (≤30 years), adult community males (<30 years), and adult community females (<30 years) were in separate FGD sessions. The results revealed that the urban area was the most affected by the epidemic (79.2%) compared to 20.8% in rural areas. The χ2 calculated was 18.183 (P<0.001). Community members exhibited varying degrees of involvement in response to the EVD epidemic in the two provinces. Community members were mostly engaged in information dissemination. However, they believe they could have contributed more if they had been fully engaged. These findings were derived from the qualitative data. The study contributes to evidence on how community involvement could help response to public health events globally, hence this study provides valuable insights for future public health interventions and response.

DOI: 10.29245/2578-3009/2023/S3.1110 View / Download Pdf

Ijeoma Igwe1, Nkechi Onyeneho1, Joseph C Okeibunor2, Michel N’da Konan Yao2, Tieman Diarra3, Mamoudou Harouna Djingarey4, Soce Fall2, Abdou Salam Gueye2

1University of Nigeria Nsukka

2World Health Organization

3Independent Consultant, Mali

4Independent Scientist, Niger

Perceptions and rumors about vaccinations can contribute to vaccine hesitancy. This study aimed to examine perceptions and rumors about the Ebola vaccine during the 10th Ebola Virus Disease outbreak in the Ituri and North Kivu provinces of the Democratic Republic of Congo. Eight hundred randomly selected respondents were surveyed with a uniform structured questionnaire. Further, we collected qualitative data through focus group discussions and using in-depth interview guides. Results revealed several misperceptions and rumors about the vaccine, which led to some level of vaccine hesitancy and refusal among the people. The acceptance rate of the vaccine was 67.3% (below the 80% threshold needed to create herd immunity in the population). More of the urban population (31.3%) than the rural population (10.4%) accepted the vaccine. Refusals were largely due to fear that the vaccine could activate other diseases in the body and could even kill. Some feared that it was a conspiracy of the government to reduce the population in the study area through forced fertility control and death, among other such concerns. In conclusion, these rumors increased mistrust, which challenged the efforts of the government and its partners to safeguard the health of the people.

DOI: 10.29245/2578-3009/2023/S3.1111 View / Download Pdf

Nkechi Onyeneho1, Joseph Okeibunor2, Ijeoma Igwe1, Ngozi Idemili Aronu1, Bailo Diallo2, Tiaman Diarra3, Barry Rodrigue2, Michel N’da Konan Yao2, Mamoudou HAROUNA DJINGAREY4, Soce Fall2

1University of Nigeria, Nsukka

2World Health Organization

3Independent Consultant, Mali

4Independent Public Health Expert, Niger

We explored the perceptions and representations of diseases in the North Kivu and Ituri provinces of the Democratic Republic of Congo to identify perceived obstacles regarding responses to the country’s Ebola virus disease (EVD) outbreak using a mix-methods approach. We surveyed a representative sample including 800 adults aged 18 years and older, held in-depth interviews with 17 community leaders, and conducted 10 focus group discussions with community members (using same-sex interviewers/discussion leaders). The results revealed the existence of several health conditions among members of the two communities. Locals consider nearly 80 of these ailments as untreatable by orthodox medicines and methods, even when symptoms are similar to EVD. Creating awareness must be considered a critical goal of community education to further educate these populations about EVD and other health problems and their respective treatments.

DOI: 10.29245/2578-3009/2023/S3.1112 View / Download Pdf

Tieman Diarra1, Nkechi Onyeneho2, Joseph Okeibunor3*, Bailo Dialloa3, Michel N’da Konan Yao3, Mamoudou Harouna Djingarey4, Soce Fall3, Dick Chamla, Abdou Salam Gueye

1Independent Consultant, Mali

2University of Nigeria, Nsukka

3World Health Organization, Switzerland

4Independent Public Health Expert, Niger

Healthcare service providers are crucial for effective responses to disease outbreaks. However, their performance is dependent on the level of system inputs, people’s perception of the system, and their willingness to use health services. This study investigated the functionality of health services and healthcare providers in the Democratic Republic of Congo during the tenth Ebola virus disease outbreak. It employed qualitative methods, including 24 in-depth interviews of healthcare providers and community leaders, and 12 focus-group discussions with community members. The responses showed that the staff did not desert the health centers and remained at their jobs. Throughout this research, only one case of abandonment of duty by a nurse was reported. The healthcare system thus played a major role in responding to the COVID-19 pandemic. However, the healthcare service providers faced several challenges. Suggestions are made to enhance the contributions of healthcare service and its providers to health emergencies in the future.

DOI: 10.29245/2578-3009/2023/S3.1107 View / Download Pdf

Aria Elahi1, Parker Alan Maddox2, Hassan Khuram3, Joshua Lewis4, Rahim Hirani4*

1The Robert Larner, MD College of Medicine at The University of Vermont

2Sidney Kimmel Medical College at Thomas Jefferson University, PA, United States

3Drexel University College of Medicine, PA, United States

4New York Medical College School of Medicine, Valhalla NY, United States

The medical response to monkeypox(mpox) is a key demonstration of how COVID-19 remodeled the global response to viruses in the medical field. As a result of the 2019 pandemic, the 2022 mpox outbreak was met with mass production of vaccines, widely available PCR testing, and increased public health and research efforts. Easy access to vaccines such as the ACAM2000 and the JYNNEOS vaccines bolstered prevention while antivirals alleviated symptoms and shortened viral duration in at-risk patients. Various methods of detection have been developed for mpox over a short period with PCR currently being used in an attempt to isolate specific strains of the virus. In this brief review, we discuss its classical presentation, and detection and treatment strategies adapted to mitigate this public health risk.

DOI: 10.29245/2578-3009/2023/1.1246 View / Download Pdf

Deborah J.W. Lee1, Tar-Choon Aw1,2,3*

1Department of Laboratory Medicine, Changi General Hospital, Singapore

2Clinical Senior Lecturer (Medicine), National University of Singapore (NUS) Yong Loo Lin School of Medicine, Singapore

3Clinical Professor (Pathology), Duke-NUS Graduate School of Medicine, Singapore

Heart failure is a major clinical problem affecting 64 million people worldwide with a 5-year mortality rate of around 50%. Patients present to the emergency department with inability to breathe properly. Heart failure is an important condition not to be missed as accurate and early diagnosis or exclusion is crucial for timely intervention. Conventionally heart failure was regarded as congestion consequent to fluid accumulation. Currently heart failure is viewed as a complex heterogeneous entity encompassing severity (clinical versus sub-clinical), onset (acute versus chronic), vascular compartment involved (intra- versus extra-vascular), besides fluid accumulation (cardiopulmonary versus generalized). There is a myriad of biomarkers that reflect different parts of heart failure pathophysiology. However, only natriuretic peptides remain as the “gold standard” against which other biomarkers are compared. This review provides a current update on the utility of natriuretic peptides in clinical practice. We will provide a brief overview of natriuretic peptides, the assays, their clinical use in heart failure, some caveats for their use (age, chronic kidney disease, obesity, heart failure with preserved ejection fraction) and highlight some emerging applications.

DOI: 10.29245/2578-3009/2023/1.1245 View / Download Pdf

Ada Alice Dona1,2#, James F Sanchez1#, Joycelynne M Palmer3, Timothy W. Synold4, Flavia Chiuppesi5, Sandra Thomas2, Enrico Caserta1,2, Mahmoud Singer1,2, Theophilus Tandoh1,2, Arnab Chowdhury3, Amrita Krishnan1, Michael Rosenzweig1, Don J Diamond5, Steven Rosen1*, Flavia Pichiorri1,2*, Sanjeet Dadwal6*

1Judy and Bernard Briskin Center for Multiple Myeloma Research, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA

2Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, CA

3Department of Computational and Quantitative Sciences, Beckman Research Institute, City of Hope, Duarte, CA

4Department of Cancer Biology, City of Hope, Duarte, CA

5Department of Experimental Therapeutics, City of Hope, Duarte, CA

6Department of Medicine, Division of Infectious Disease, City of Hope, Duarte, CA USA

#These authors contributed equally to this work.

Background: Vaccines for SARS-CoV-2 have been considerably effective in reducing rates of infection and severe COVID-19. However, many patients, especially those who are immunocompromised due to cancer or other factors, as well as individuals who are unable to receive vaccines or are in resource-poor countries, will continue to be at risk for COVID-19. We describe clinical, therapeutic, and immunologic correlatives in two patients with cancer and severe COVID-19 who were treated with leflunomide after failing to respond to standard-of-care comprising remdesivir and dexamethasone. Both patients had breast cancer and were on therapy for the malignancy.

Methods: The protocol is designed with the primary objective to assess the safety and tolerability of leflunomide in treating severe COVID-19 in patients with cancer. Leflunomide dosing consisted of a loading dose of 100 mg daily for the first three days, followed by daily dosing, at the assigned dose level (Dose Level 1: 40 mg, Dose Level -1, 20 mg; Dose Level 2, 60 mg), for an additional 11 days. At defined intervals, serial monitoring of blood samples for toxicity, pharmacokinetics, and immunologic correlative studies were performed, as well as nasopharyngeal swabs for PCR analysis of SARS-CoV-2.

Results: Preclinically, leflunomide impaired viral RNA replication, and clinically, it led to a rapid improvement in the two patients discussed herein. Both patients completely recovered, with minimal toxicities; all adverse events experienced were considered unrelated to leflunomide. Single-cell mass-cytometry analysis showed that leflunomide increased levels of CD8+ cytotoxic and terminal effector T cells and decreased naïve and memory B cells.

Conclusions: With ongoing COVID-19 transmission and occurrence of breakthrough infections in vaccinated individuals, including patients with cancer, therapeutic agents that target both the virus and host inflammatory response would be helpful despite the availability of currently approved anti-viral agents. Furthermore, from an access to care perspective, especially in resource-limited areas, an inexpensive, readily available, effective drug with existing safety data in humans is relevant in the real-world setting.

DOI: 10.29245/2578-3009/2023/1.1241 View / Download Pdf

Salil Chowdhury1, Daniel Garrido2, Dina Halegoua-DeMarzio3, Christopher Roth4, Hie-Won Hann3*

1Thomas Jefferson University Hospital, Department of Internal Medicine, Philadelphia, PA

2Cooper University Hospital, Digestive Health Institute, Camden, NJ

3Thomas Jefferson University Hospital, Division of Gastroenterology and Hepatology, Philadelphia, PA

4Thomas Jefferson University Hospital, Department of Radiology, Philadelphia PA

Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, with chronic hepatitis B virus (HBV) infection being an important risk factor for HCC. While nucleos(t)ide analog (NA) therapy has succeeded in suppressing HBV replication and decreasing the risk of HCC in patients with HBV infection, there remains a persistent risk of HCC in those patients. Furthermore, previous studies have highlighted worse survival in patients who developed HCC while on successful NA therapy compared to those who developed HCC without previous NA treatment.

 We conducted a long-term, retrospective case study in 5 patients observed between 10 and 25 years, to further explore the poor outcomes in patients with HBV-associated HCC with or without previous NA therapy. Our study highlights the aggression and recurrence of HCC in patients with HBV infection, well-suppressed on NA therapy. The results of our observation emphasize the need for early referral for liver transplantation in these select patients.

DOI: 10.29245/2578-3009/2023/1.1242 View / Download Pdf

Marc Roder1 and Sascha Kahlfuss1,2,3,4*

1Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

2Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

3Health Campus Immunology, Infectiology and Inflammation (GCI3), Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

4 Center for Health and Medical Prevention (CHaMP), Otto-von-Guericke-University, Magdeburg, Germany.

The energy metabolism was demonstrated to directly modulate immune cell function and thereby physiological and detrimental immune responses. In addition, the field of immunometabolism is vastly growing. However, yet there remain fundamental scientific questions in the field, which require the organization of national and international networks as well as the implementation of immunometabolism into curricula, scientific societies, and immunological routine diagnostics to hold the promise of personalized medicine to our patients within the next decade.

DOI: 10.29245/2578-3009/2022/4.1243 View / Download Pdf

Matthew P. Hardy1*, Tony Rowe1, and Sandra Wymann2

1CSL, Bio21 Institute, Victoria, Australia

2CSL, CSL Biological Research Centre, Bern, Switzerland

Human Complement Receptor 1 (CR1/CD35) is a potent negative regulator of the complement system. Its mechanism of action is through interaction with the complement activation fragments, C3b and C4b to mediate decay acceleration of the C3 and C5 convertase complexes as well as cleavage of both ligands into inactive fragments via cofactor activity. The result is inhibition of the classical, lectin, and alternative complement pathways. This article will focus on recombinant soluble forms of CR1 that have been generated as potential therapeutics for complement-mediated disorders. Specifically, we will review and contrast the in vitro and in vivo properties of: sCR1 (BRL55730/TP10/CDX-1135), the soluble full-length extracellular domain of human CR1; sCR1-sLex (TP20), a glyco-engineered version of sCR1 additionally targeted to activated endothelium; APT070 (Mirococept), a CR1 fragment conjugated to a myristoylated peptide to enhance tissue targeting; and CSL040, a soluble truncated version of the CR1 extracellular domain which exhibits altered potency and pharmacokinetic properties as compared to the parental molecule. The data obtained from studies on the effects of these CR1-based molecules in animal models of disease and their therapeutic applications will also be discussed.

DOI: 10.29245/2578-3009/2022/4.1240 View / Download Pdf

Kushal Gandhi1#, Nathan Joshua Manales1#, Asley Sanchez1#, Srikanth Mukkera1*, Anusha Ammu1, Janine Klar1, Alex Gibson1, Evangelina Santiago2, Ailena Mulkey2, Jammie Holland2, Maneesh Mannem1, Lakshmi P. Alahari1, and John Garza1,3

1 School of Medicine, Texas Tech University Health Sciences Center (TTUHSC) at the Permian Basin, TX, USA

2 Clinical Research institute at the Permian Basin, Texas Tech University Health Sciences Center – Permian Basin, TX, USA

3 The University of Texas Permian Basin, Odessa, TX, USA

# Authors contributed equally

Background: In the spring of 2021, coronavirus disease 2019 (COVID-19) vaccines were approved and distributed in the United States for the public to combat the COVID-19 pandemic, but their rapid development leaves some questions unanswered. Vaccine efficacy has always been a point of interest for individuals with rheumatological diseases that take immunosuppressants. This study investigates the vaccine efficacy of two COVID-19 mRNA-based vaccines, Moderna and Pfizer, in subjects in West Texas patients with autoimmune diseases.

Materials and Methods: Blood was collected from Texas Tech University employees who received both doses of COVID-19 vaccines within the past nine months. Subjects were separated into either a group with a known history of rheumatic disease (n=18) or those without (n=18). The samples were analyzed for serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels using specific enzyme-linked immunoassay kits, and a neutralizing antibody test using a surrogate virus was conducted as well. Results were analyzed using the Mann-Whitney U test (unpaired, two-tailed).

Results: There was no significant difference in serum IgG and IgA levels between the control and rheumatologic disease groups, but there were significant differences in serum IgM levels. All subjects cleared the threshold for the neutralizing antibody test.

Conclusion: The relatively similar serum IgG levels and the 100% detection rate of effective neutralizing antibodies across both groups indicate promising signs of serological response for subjects with autoimmune conditions, but the relatively low serum IgA and IgM levels of the study the group warrants further investigation.

DOI: 10.29245/2578-3009/2022/3.1235 View / Download Pdf

Baofa Yu, MD1,2,3,4*, Qiang Fu, MS3, Yan Han, MS3, Jian Zhang3, Dong Chen,MD3

1Immuno Oncology Systems, Inc., San Diego, CA 92122, USA

2TaiMei Baofa Cancer hospital, Dongping, Shandong Province, China, 271500

3Jinan Baofa Cancer hospital, Jinan, Shandong Province, China,250000

4Beijing Baofa Cancer Hospital, Beijing, China

Aim: To study the immunity reaction in tumor by intratumoral injection with a drug PYM and DNP, where it produces abscopal effect by the expression of immunological genes of tumor on home side (left side) while it brings a similar expression of same genes in tumor on opposite side (right side) of mice.

Method: Prepare each tumor on left side of 6 mice and injected intratumoral with a PYM+DNP and PYM control on day 1 and 7. Two day later of day 1, one of groups mice were inoculated with 0.2ml of H22 cells (105/ml) again on the right underarms as opposite side for controls. On day15, the tumor on bilateral sides were excised for qPCR measurement.

Result: It showed that inflammation with the expression of the CoL1a1, CD4, IL12aÂ, TGFb1Â, Elastin, Elastin, Cox2, CD11b/c, CD8, TNFa in different groups; The inflammation in both side of tumor but these is not only a increasing expression of Collal, CD4, IL12aÂ, TGFb1Â, Elastin, NFKB, Cox2, CD11c, CD8 and TNFa in tumor on home side of mice treated with PYM+DNP but also a similar an increasing expression of same genes in tumor on opposite side of mice which not treated at all. In the control group, it showed that inflammation without an expression of all factors related above immunity genes in both tumor on home treated with PYM only and opposite side of mice which not treated at all.

Conclusion: It indicated that PYM and hapten of DNP can induce an inflammation with stimulation of immunity reaction with the expression of the CoL1a1, CD4, IL12aÂ, TGFb1Â, Elastin, Elastin, Cox2, CD11b/c, CD8, TNFaÂ, which resulted in an abscopale effect. PYM can induce an inflammation but without expression of immuno genes, therefore, hapten is playing an important role with PYM in the special immunity reaction.

DOI: 10.29245/2578-3009/2022/3.1236 View / Download Pdf

Lisa M. James1,2,3, Apostolos P. Georgopoulos1,2,3,4*

1The HLA Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA

4Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

The association of Human Leukocyte Antigen (HLA) with melanoma has been well documented. Similarly, the outcome of checkpoint blockade immunotherapy (CBI) in melanoma depends, to some extent, on the HLA genotype of the patient. Although specific favorable (or unfavorable) HLA alleles for CBI outcome for melanoma have been identified, there is currently no reliable way to predict a positive, neutral or negative melanoma CBI outcome for other alleles. Here we used an immunogenetic epidemiological approach to identify HLA alleles whose frequency is negatively (or positively) associated with melanoma prevalence (protective or susceptibility alleles, respectively). The findings demonstrated that, indeed, HLA alleles that are negatively associated with melanoma prevalence in the population have been associated with good CBI outcome at the individual level and, conversely, HLA alleles that are positively associated with melanoma prevalence have been associated with poor CBI outcome in individuals. Given this good prediction of CBI cancer immunotherapy by specific immunogenetically discovered HLA alleles, we used this epidemiologic immunogenetic approach to identify more HLA Class I and II alleles protective (or susceptibility) for melanoma which would thus be good predictors of CBI outcomes in those cancers. This is a new approach to successfully (a) identify HLA protective or susceptibility alleles for melanoma, and (b) use that information in anticipating outcomes in CBI cancer immunotherapy.

DOI: 10.29245/2578-3009/2022/2.1238 View / Download Pdf

Gavin Yuen*, Saundarai Bhanot#, Jeremy Steen, Minahil Syed, Austin Mardon#

Sharpen the Quill, Ontario, Canada

Vaccination is a powerful inducer of immunity against SARS-CoV-2 and its recent variants. However, it is important to expand the defensive repertoire against this virus as vaccination is not always efficacious or accessible to everyone. Protein therapeutics in the form of monoclonal antibodies have been used to neutralize the Spike protein, but their efficacy has been limited with rapidly evolving mutations. Cocktail antibodies have been used to combat antigenic escape through diversifying antigen recognition and the overall neutralization capacity. However, the production of cocktail antibodies can be costly and requires a high dosage to achieve the desired therapeutic effect. Alternatively, bispecific antibodies have been used, which contain two recognition specificities within the same molecule. This effectively reduces the cost of production and dosage required to achieve a target therapeutic effect. Bispecific antibodies were reported to bind SARS-CoV-2 antigen with nanomolar affinities. The neutralization potentials (IC50 values) within the same studies were generally more efficacious than their cocktail antibody counterparts. Some studies showed that bispecific antibodies could also confer additional neutralization effector functions, such as recruiting the complement system. Although the recognition of variants was diverse, to our knowledge, there is no data to suggest that bispecific antibodies have a broader recognition of variant strains than cocktail antibodies. Future studies should aim to explore the clinical benefits of bispecific antibodies for SARS-CoV-2 and the emerging variant strains to better understand its benefits in treatment.

DOI: 10.29245/2578-3009/2022/2.1237 View / Download Pdf

Apostolos P. Georgopoulos1,2,3,4*, Lisa M. James1,2,3

1The HLA Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA

4Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

Human leukocyte antigen (HLA) genes have been associated with susceptibility and protection against a number of cancers. Here we used an immunogenetic epidemiological approach to evaluate the overall influence of 127 HLA Class I and II alleles on 30 types of cancer. We found a preponderance of protective alleles (negatively correlated with cancer prevalences), especially for HLA Class I. Of the 30 cancers investigated, 13 were associated with mostly protective HLA effects whereas only 2 were associated with mostly susceptibility HLA alleles. Taken together, these findings highlight the broad influence of HLA on cancer and the complexity of HLA-cancer associations.­­

DOI: 10.29245/2578-3009/2022/2.1227 View / Download Pdf

Raquel García-Belmonte, Daniel Pérez-Núñez, Yolanda Revilla*

Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Microbes in Health and Welfare Department, c/ Nicolás Cabrera, 1, 28049 Madrid, Spain

DOI: 10.29245/2578-3009/2022/2.1233 View / Download Pdf