INTRODUCTION: Outcomes after SARS-CoV-2 Omicron infection in patients with heart failure (HF) and ischaemic heart disease (IHD) remain poorly defined. METHOD: In a highly vaccinated cohort of adult Singapore citizens and permanent residents, we used Cox proportional hazards models (adjusted for sociodemographic variables and comorbidities) to compare the risks of Omicron infection, COVID-19- related hospitalisation, and severe COVID-19 between indivi-duals with HF or IHD and matched controls without these conditions. RESULTS: From national databases, we identified 15,426 HF patients matched 1:∼3 to 41,221 controls, and 110,442 IHD patients matched 1:∼2 to 223,843 controls. Over 80% of HF and IHD patients had received at least 3 vaccine doses. During the Omicron-predominant period, both HF and IHD cohorts demonstrated higher adjusted risks of COVID-19 hospitalisation compared with matched controls (HF: adjusted hazard ratio [aHR] 1.77, 95% confidence interval [CI] 1.65-1.90; IHD: aHR 1.21, 95% CI 1.17-1.26). Among those with at least 1 HF-or IHD-related admission in the prior year, hospitalisation risk was further elevated (HF: aHR 1.27, 95% CI 1.13-1.42; IHD: aHR 1.11, 95% CI 1.01-1.23). Receipt of ≥3 vaccine doses was associated with substantially lower risk of severe COVID-19 versus only 2 doses (HF: aHR 0.35, 95% CI 0.28-0.43; IHD: aHR 0.27, 95% CI 0.23-0.32). A fourth dose conferred additional reductions in infection and adverse outcomes, though CIs for infection overlapped with those for 3 doses. CONCLUSION During Omicron predominance, HF and IHD patients experienced greater risk of COVID-19 hospitalisation and severe COVID-19 versus matched controls. Booster vaccinations attenuated these risks. Individuals with recent HF/IHD admissions should be prioritised for receipt of booster vaccine doses.
Humans ; COVID-19/complications* ; Male ; Heart Failure/complications* ; Myocardial Ischemia/complications* ; Female ; Middle Aged ; Hospitalization/statistics & numerical data* ; Aged ; COVID-19 Vaccines/administration & dosage* ; Singapore/epidemiology* ; SARS-CoV-2 ; Proportional Hazards Models ; Adult ; Case-Control Studies ; Vaccination/statistics & numerical data*

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promises, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
Colorectal Neoplasms/immunology* ; Humans ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy, Adoptive/methods* ; Tumor Microenvironment/immunology* ; Animals

OBJECTIVE

Given that rabies remains endemic in the Philippines despite government interventions and the pandemicrelated restrictions have hampered its surveillance, this study aimed to estimate the effect of human population, anti-rabies vaccination efforts, and COVID-19 situation on the spread of rabies cases in the districts of Davao City, Philippines.

A retrospective study of the canine records at Davao City Veterinarians’ Office was done from January 2018 to June 2021. Monthly rabies cases were ascertained, and the effect of the human population, COVID-19 season, and vaccination ratio on rabies cases was estimated using panel regression models adjusting for confounding factors.

The reporting of rabies cases was lower during COVID-19 than during the non-COVID-19 season, with an IRR of 0.52 [95% confidence interval (CI): 0.33–0.82]. Furthermore, rabies cases increased by 2.23% (95% CI: 0.60–3.89) per 1% increase in vaccination ratio. Additionally, high-population districts recorded more rabies cases than low-population districts.

Consistency in monitoring rabies cases during the pandemic is suggested as a roadmap for future program initiatives. Vaccination efforts should be reinforced to increase rabies awareness and ensure early response to emerging diseases. Moreover, highpopulated districts should be prioritized in implementing rabies control interventions to gain optimal development.

BACKGROUND

Cervical cancer remains to be the second leading cancer and cause of cancer-related deaths among Filipino women despite the use of the Papanicolaou screening. Latest research has shown that the human papillomavirus (HPV) is a necessary cause of cervical cancer. With major morbidity and high mortality rates associated with HPV infection and cervical cancer, several modes of primary and secondary forms of prevention have to be implemented. Among the primary modes of prevention is the administration of the preventive vaccine, which has consistently shown to decrease substantially HPV disease and cervical cancer rates in developed countries. In our country, before a successful vaccination, program is implemented, several sociocultural issues have to be addressed. Knowledge, attitude, and motivational factors are vital in determining acceptance of the vaccine. One relevant setting is exploring the willingness of mothers to get their female children vaccinated even before they become sexually active.

The aim of the study was to determine the association of the knowledge, attitude, and motivational factors of mothers on their willingness for their female children aged 9–13 years to undergo HPV vaccination at a tertiary government hospital.

This was a cross-sectional study that was carried out at a government institution.

The population consisted of 352 mothers with female children aged 9–13 years consulting the outpatient clinics at the department of obstetrics and gynecology at a tertiary government hospital.

A pretested and validated survey was given to 352 respondents. They were asked to answer a self-administered questionnaire that included sociodemographic, reproductive, sexual history variables, knowledge, and attitude, and motivational factors toward the disease and the associated vaccine.

Using the survey proportion estimation methods, the prevalence of women who were willing to enroll their daughters for HPV vaccination was 97.18% (n = 42, 95% confidence interval [CI]: 94.91 to 98.46%). It can be noted that only a third of the sample had high knowledge on the vaccine and its use 34.93% (n = 124, 95% CI: 30.25 to 39.92%). More women who reached college level (χ2: 5.67) and also those whose youngest child was between 11 and 13 years old (χ2: 8.82)-had higher knowledge scores than otherwise. Those who have an annual income of greater than or equal to P 60,000 (χ2: 16.55) and are non-Catholic (χ2: 18.77) – also appeared to have higher knowledge ratings on the questionnaire. Women who never to a few times a year attend church-related activities had higher knowledge scores compared to women who were more frequent goers (χ2: 16.33). For the attitude toward the vaccine, more mothers believed that getting the vaccine would not have an effect on a girl’s sexual activity and most agreed that they would not be viewed as bad parents. Most women also did not believe that religion would affect their willingness to vaccinate their children. There was an association in the degree of agreement between negative and positive attitudes from the Chi-square test performed (χ2: 7.44, P: 0.01). There were more agreeing responses from factors determining positive attitude and more disagreeing responses in the factors determining negative attitude. With regard to motivational factors, more women agreed that the cost was prohibitive and that they were more willing if only two doses would be required for their daughters. They were also not concerned about what other parents may think about getting the vaccine. Most answered that they were willing to follow their doctors’ recommendations and they have trust in vaccine manufacturers. Most women were also concerned that their daughters may get cervical cancer in the future. There was no difference in the proportion of agreeing responses between positive and negative motivating factors among the study participants (Z: 0.30, P: 0.79). This suggested that these factors could be important predictors of willingness to use vaccination on their children. Based on the crude odds ratios from the logistic regression, the likelihood of being willing to administer HPV vaccine to their children was almost twice as the knowledge score and scores on the positive attitude items increased, and was found to be statistically significant. At the same time, the odds of willingness increased by more than twice as the score on the negative attitude items decreased, and was also significant. There was no noted association for the other predictors of the association.

The role of knowledge and attitudes on the negative perceptions on the vaccine were important predictors of the willingness of mothers to have their female children vaccinated against HPV infection.

Sporadic late-onset nemaline myopathy （SLONM） is a rare， acquired， and treatable myopathy with a subacute or chronic progressive clinical course， characterized by asymmetric muscle atrophy and weakness in the axial and limb muscles， with or without involvement of respiratory and cardiac muscles. The only definitive diagnostic method at present is the identification of rods accumulation in muscle fibers by muscle biopsy pathology. This article provides a review of the clinical manifestations， diagnostic evaluations， muscle pathology， and advances in the treatment of SLONM.
Immunotherapy

Autoimmune encephalitis（AE）is a type of brain inflammation caused by the immune system mistaking autoantigens expressed in the central nervous system for foreign antigens，thereby resulting in abnormal immune response that affects brain parenchyma（cortex or deep gray matter and white matter）and may involve the meninges and spinal cord. This disease is not an infectious inflammatory disease caused by pathogen invasion and is fundamentally different from purulent encephalitis and viral encephalitis，and it can occur in different populations such as children，adolescents，and adults. A recent epidemiological study from the United States shows that there might be a higher prevalence rate of AE，and the prevalence rate of AE was 13.7/100 000 in this population-based study，with no significant difference from the prevalence rate of infectious encephalitis. Since the discovery of anti-N-methyl-D-aspartate（NMDA）receptor antibodies，many patients who experience mental symptoms with rapid progression，abnormal behavior，seizures，or unexplained coma have been diagnosed with AE. The onset of symptoms is usually unclear，which might be similar to mental illness，but then the disease often progresses rapidly and causes damage to brain parenchyma and even loss of consciousness and coma，which usually requires intensive care. Therefore，a comprehensive and systematic understanding of AE is of great significance for clinicians to achieve early identification，diagnosis，and treatment and help patients obtain a good prognosis. This article aims to provide a comprehensive overview of existing research findings of AE in terms of its past，present，and future development and from cognitive limitations to the leap towards precision treatment，in order to provide assistance for diagnosis and treatment among clinicians.
Immunotherapy

BACKGROUND

Vaccine hesitancy among senior citizens remains common in many countries. This was significantly observed during the COVID-19 pandemic in Dauis, Bohol, Philippines. However, there is limited research on the factors influencing this hesitancy.

This study aimed to identify the determinants associated with COVID-19 vaccine hesitancy among senior citizens in the municipality of Dauis, Bohol.

This case-control study employed a modified survey questionnaire adapted from relevant literatures. A total of 497 registered senior citizens participated, of whom 331 were vaccinated against COVID-19 and 166 were unvaccinated. The study determined the socio-demographic factors, health status, and perceptions of COVID-19 vaccine safety. Bivariate and multivariable logistic regression analyses were used to identify factors associated with vaccine hesitancy.

The study found that respondents aged 84 and older were significantly more likely to exhibit vaccine hesitancy (p = 0.018, OR = 7.817). In contrast, factors associated with a reduced likelihood of hesitancy included having tertiary education (p = 0.012, OR = 0.239), a low income (p = 0.042, OR = 0.138), receiving an annual flu vaccine (p = 0.020, OR = 0.328), and perceiving the COVID-19 vaccine as safe (p = 0.000, OR = 0.032).

Age is a significant determinant of COVID-19 vaccine hesitancy. Educational attainment, monthly income, receipt of annual influenza vaccine and perception on vaccine safety were found to be influential determinants. These findings offer valuable insights for evidence-based interventions to enhance vaccine acceptance to this vulnerable population.

BACKGROUND

The COVID-19 pandemic significantly impacted global health, especially among older adults at higher risk for severe illness. Despite the benefits of vaccination, booster vaccine hesitancy posed a barrier to optimal protection in the elderly population.

This study aimed to identify factors associated with COVID-19 booster vaccine hesitancy among geriatric patients at the Family Medicine Outpatient Clinic of Region 1 Medical Center.

An analytic, cross-sectional study was conducted with 183 geriatric patients aged 60 and above who had received the primary COVID-19 vaccine series. Data were collected using a 25-item questionnaire addressing sociodemographic information, medical history, COVID-19 knowledge, and vaccine attitudes. Statistical analyses, including chi-square tests and logistic regression, identified factors influencing booster vaccine hesitancy.

The majority of participants were between the ages of 60-69 (66.7%, n=122) and predominantly female (69.4%, n=127). High hesitancy rates were notably observed among elderly females (75.6%), individuals with lower educational attainment (79.7%), and single individuals (93.3%). Other significant factors included hypertension (76.5%) and the absence of prior influenza (81.5%) or pneumococcal (75.9%) vaccinations.

These findings highlight the critical need for targeted educational efforts to mitigate COVID-19 vaccine hesitancy within specific subgroups, particularly elderly females, those with lower education levels, and individuals with certain health conditions. By implementing personalized outreach and emphasizing the advantages of vaccination, stakeholders can enhance vaccine uptake and improve health outcomes for this vulnerable segment of the population.

Rabies remains a persistent public health issue in the Philippines, despite the existence of national and local policies and programs aimed at addressing its eradication. The viral disease, which elicits fatality yet is preventable, disproportionately affects rural areas, especially geographically isolated and disadvantaged area due to the junction of socio-cultural and technical challenges. This commentary article explores the myriad of barriers to rabies prevention and control, including poverty, cultural beliefs, limited health literacy, health delivery, and access inequity. However, the implementation of Rabies Act of 2007, which mandates mass vaccination, education, and the establishment of Animal Bite Treatment Centers (ABTCs), has gaps in the implementation that compromises the program’s sustainability and effectiveness. Deep-rooted cultural practices and beliefs delay or, more so replace evidence-informed medical practices, while geographic isolation and underfunded healthcare facilities hinder optimal provision of care. Moreover, interagency coordination and fragmented reporting surveillance systems further complicate effective rabies control. To address the gaps, this paper advocates for a culturally tailored and community-centered One Health approach that addresses both social and technical aspects of rabies prevention. Important recommendations include decentralizing ABTCs, sustaining vaccination programs with local government support and funding, integrating rabies education into schools and community outreach, and intensifying through multisectoral collaboration both government and nongovernment institutions. Achieving a rabies-free country requires not only biomedical interventions but also a holistic approach – equitable access to healthcare, trust building in communities, and long-term political commitment. In this manner, regardless of location and socioeconomic status, it ensures that this viral disease will be controlled and prevented.