Diseases, Volume 12, Issue 2 (February 2024) – 11 articles

Background: Checkpoint inhibitor (CPI)-associated diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE) that presents with variable clinical manifestations. Data about its pathogenesis have not yet been adequately studied. Methods: Applying the recently updated diagnostic criteria from the American Diabetes Association, we retrospectively reviewed the medical records of all CPI-treated patients referred to our endocrinological unit for managing their endocrine irAEs and analyzed the incidence of CPI-DM, its clinical characteristics, and its management. Results: Among the 326 CPI-treated patients with endocrine irAEs, 4 patients met the updated criteria for the diagnosis of CPI-DM, representing 1.22% of all endocrine irAEs in our cohort. These four patients presented with distinct clinical scenarios regarding the irAE onset, the underlying malignancy, the administered CPI regimen, and the type of circulating autoantibodies. Conclusion: The variable presentation of CPI-DM and the non-standard sensitivity of the presence of the type 1 DM traditional autoantibodies highlight the need for distinct guidelines and increased awareness of its diagnosis and management. Full article

Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary. Full article

Background: Catheter ablation (CA) for atrial fibrillation (AF) is superior to antiarrhythmic drugs in maintaining sinus rhythm. Novel evidence suggests that increasing the time between the first diagnosis of AF and ablation, or diagnosis-to-ablation time (DAT), is a predictor for AF recurrence post-ablation. Purpose: Our primary objective was to investigate the relationship between DAT and AF recurrence after a first ablation. Methods: Patients with AF who underwent CA in our center were enrolled consecutively, and a retrospective analysis was performed. DAT was treated as a continuous variable and reported as a median for the group with recurrence and the group without recurrence. DAT was also considered as a categorical variable and patients were stratified into three categories: DAT < 1 year, DAT < 2 years, and DAT < 4 years. Results: The cohort included 107 patients, with a mean age of 54.3 ± 11.7 years. Mean DAT was significantly longer in those with AF recurrence: 4.9(3.06) years versus 3.99(3.5) (p = 0.04). The Kaplan–Meier curve revealed a higher likelihood of AF-free status over time for patients with DAT < 2 years compared to those with DAT > 2 years (p = 0.04). Cox multivariate analysis indicated that left atrial volume index (LAVI), obstructive sleep apnoea (OSA), and DAT > 2 years were independently associated with AF recurrence after a single AF ablation procedure (p = 0.007, p = 0.02, and p = 0.03, respectively). Conclusion: A shorter duration between the first AF diagnosis and AF ablation is associated with an increased likelihood of procedural success after a single AF ablation procedure. Full article

Introduction: This is a case report of a patient with neuropathic corneal pain after coronavirus disease 2019 (COVID-19) infection. Methods: A previously healthy 27-year-old female presented with bilateral eye pain accompanied by increased light sensitivity 5 months after COVID-19 infection. She was diagnosed with neuropathic corneal pain based on clear corneas without fluorescein staining, alongside the presence of microneuromas, dendritic cells, and activated stromal keratocytes identified bilaterally on in vivo confocal microscopy. Results: The patient’s tear nerve growth factor, substance P, and calcitonin gene-related peptide levels were 5.9 pg/mL, 2978.7 pg/mL, and 1.1 ng/mL, respectively, for the right eye and 23.1 pg/mL, 4798.7 pg/mL, and 1.2 ng/mL, respectively, for the left eye, suggesting corneal neuroinflammatory status. After 6 weeks of topical 0.1% flurometholone treatment, decreased microneuroma size, less extensive dendritic cells, and reduced tear nerve growth factor and substance P levels were observed. The scores on the Ocular Pain Assessment Survey showed an improvement in burning sensation and light sensitivity, decreasing from 80% and 70% to 50% for both. Conclusions: Neuropathic corneal pain is a potential post-COVID-19 complication that warrants ophthalmologists’ and neurologists’ attention. Full article

mRNA COVID-19 vaccines have been reported as protecting against COVID-19 and reducing its severity, and we have recognized post-vaccination symptoms recently. This research investigates the clinical trajectories of ocular disorders in a 51-year-old female who received a second dose of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine. Exhibiting fever and blurred vision within 24 h post-vaccination, with progressive blurry vision over two months, she underwent in-depth ophthalmologic examinations, revealing intraocular cellular infiltration in anterior chamber, vitreous opacity, and frosted branch angiitis in both eyes. Comprehensive evaluations, including systemic workups as well as ocular and blood specimen analyses, excluded autoimmune and infectious etiologies, consolidating the diagnosis of vaccine-induced ocular inflammation. Despite adherence to prevailing therapeutic protocols, her condition showed no significant improvement over 18 months, pointing to a possible long post-COVID vaccination syndrome. Such persistent sequelae underscore the need for detailed studies to discern the interactions between vaccine-induced immune responses and the development of post-vaccination sequelae. Continual documentation of patients with long post-COVID vaccination syndrome is now essential to better understand the vaccine’s immunological effects, aiding in improving global vaccination strategies. Full article

Background: Automated rhythm detection on echocardiography through artificial intelligence (AI) has yet to be fully realized. We propose an AI model trained to identify atrial fibrillation (AF) using apical 4-chamber (AP4) cines without requiring electrocardiogram (ECG) data. Methods: Transthoracic echocardiography studies of consecutive patients ≥ 18 years old at our tertiary care centre were retrospectively reviewed for AF and sinus rhythm. The study was first interpreted by level III-trained echocardiography cardiologists as the gold standard for rhythm diagnosis based on ECG rhythm strip and imaging assessment, which was also verified with a 12-lead ECG around the time of the study. AP4 cines with three cardiac cycles were then extracted from these studies with the rhythm strip and Doppler information removed and introduced to the deep learning model ResNet(2+1)D with an 80:10:10 training–validation–test split ratio. Results: 634 patient studies (1205 cines) were included. After training, the AI model achieved high accuracy on validation for detection of both AF and sinus rhythm (mean F1-score = 0.92; AUROC = 0.95). Performance was consistent on the test dataset (mean F1-score = 0.94, AUROC = 0.98) when using the cardiologist’s assessment of the ECG rhythm strip as the gold standard, who had access to the full study and external ECG data, while the AI model did not. Conclusions: AF detection by AI on echocardiography without ECG appears accurate when compared to an echocardiography cardiologist’s assessment of the ECG rhythm strip as the gold standard. This has potential clinical implications in point-of-care ultrasound and stroke risk stratification. Full article

HLA-G is the checkpoint molecule involved in the suppression of the immune response. Increased expression of HLA-G and its ILTs receptors have been correlated with tumor progression in various cancer types. In head and neck squamous cell carcinoma (HNSCC) tumors, the effect of HLA-G, ILT2 and ILT4 expression on cancer development has to be explained. The 34 HNSCC patients and 98 controls were genotyped for the HLA-G 14 bp ins/del polymorphism. In HNSCC lesions, HLA-G, ILT2 and ILT4 mRNA expression was analysed using real-time PCR. The association between HLA-G, ILT2 and ILT4 mRNA expression and clinical variables (age at onset, TNM staging system and p16 positivity) was also evaluated. No genetic association between the HLA-G 14 bp ins/del and HNSCC risk was detected (p > 0.05). However, in the non-metastatic HNSCC group, a significantly higher HLA-G mRNA expression was noted in tumors in the T4 stage compared to those in the T1 and T2 stages (p = 0.0289). ILT2 mRNA expression was significantly increased in non-metastatic vs. metastatic tumors (p = 0.0269). Furthermore, a significantly higher ILT4 mRNA expression was noted in tumors in the T1+T2 stage compared to those in the T3 stage (p = 0.0495). Our results suggest that the HLA-G molecule creates an immunological microenvironment involved in HNSCC development. Full article

Patients receiving B-cell-depleting therapies (BCDT) are at an increased risk for severe COVID-19. Passive antibody therapy (PAT), including COVID-19 convalescent plasma (CCP) and monoclonal antibodies (mAb), may be an effective treatment in this population. Real-world data on PAT effectiveness are limited. To evaluate response to PAT measured through 90-day all-cause morbidity and mortality, we performed a retrospective review of patients who contracted COVID-19 within a year from the last BCDT. From 64 included patients, the majority were Caucasians (95%), female (56%), vaccinated (67%), treated outpatients (64%), with multiple comorbidities. Examined BCDT were rituximab (55%), obinutuzumab (33%), ocrelizumab (11%) and ofatumumab (1%), used for underlying hematological malignancy (HEM) (40%), multiple sclerosis (34%), and rheumatoid arthritis (16%). Of seven deceased patients, three died from COVID-19. All three were elderly males with multiple comorbidities, treated inpatient for severe COVID-19. Four of 41 patients treated as outpatients were hospitalized for non-COVID-19-related reasons. All deceased and hospitalized patients had an underlying HEM. All but one were on rituximab. PAT may be an effective treatment for patients receiving BCDT, especially if given early for non-severe disease. Patients with underlying HEM may be at increased risk for severe disease compared with others receiving the same BCDT. Full article

About half of the world’s population is at risk of dengue infection. Epidemics of dengue fever have caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines and searching multiple databases, including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0–17 years old). Quality assessment was analyzed using the Cochrane Collaboration criteria, while data synthesis was conducted using thematic analysis and meta-analysis. Among the 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. The CYD-TDV (Dengvaxia^®) and Tekade (TAK-003) vaccines showed strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines showed promising efficacy and immune response, particularly against severe manifestations. Full article

Zika virus (ZIKV) and chikungunya virus (CHIKV) are arthropod-borne viruses with significant pathogenicity, posing a substantial health and economic burden on a global scale. Moreover, ZIKV-CHIKV coinfection imposes additional therapeutic challenges as there is no specific treatment for ZIKV or CHIKV infection. While a growing number of studies have documented the ZIKV-CHIKV coinfection, there is currently a lack of conclusive reports on this coinfection. Therefore, we performed a systematic review and meta-analysis to determine the true statistics of ZIKV-CHIKV coinfection in the global human population. Relevant studies were searched for in PubMed, Scopus, and Google Scholar without limitation in terms of language or publication date. A total of 33 studies containing 41,460 participants were included in this meta-analysis. The study protocol was registered with PROSPERO under the registration number CRD42020176409. The pooled prevalence and confidence intervals of ZIKV-CHIKV coinfection were computed using a random-effects model. The study estimated a combined global prevalence rate of 1.0% [95% CI: 0.7–1.2] for the occurrence of ZIKV-CHIKV coinfection. The region of North America (Mexico, Haiti, and Nicaragua) and the country of Haiti demonstrated maximum prevalence rates of 2.8% [95% CI: 1.5–4.1] and 3.5% [95% CI: 0.2–6.8], respectively. Moreover, the prevalence of coinfection was found to be higher in the paediatric group (2.1% [95% CI: 0.0–4.2]) in comparison with the adult group (0.7% [95% CI: 0.2–1.1]). These findings suggest that the occurrence of ZIKV-CHIKV coinfection varies geographically and by age group. The results of this meta-analysis will guide future investigations seeking to understand the underlying reasons for these variations and the causes of coinfection and to develop targeted prevention and control strategies. Full article

Lean body mass is a significant component of survival from sepsis. Several equations can be used for calculating lean body mass based on age, sex, body weight, and height. We hypothesized that lean body mass is a better predictor of outcomes than the body mass index (BMI). This study used a multicenter cohort study database. The inclusion criteria were age ≥18 years and a diagnosis of sepsis or septic shock. BMI was classified into four categories: underweight (<18.5 kg/m²), normal (≥18.5–<25 kg/m²), overweight (≥25–<30 kg/m²), and obese (≥30 kg/m²). Four lean body mass equations were used and categorized on the basis of quartiles. The outcome was in-hospital mortality among different BMI and lean body mass groups. Among 85,558 patients, 3916 with sepsis were included in the analysis. Regarding BMI, in-hospital mortality was 36.9%, 29.8%, 26.7%, and 27.9% in patients who were underweight, normal weight, overweight, and obese, respectively (p < 0.01). High lean body mass did not show decreased mortality in all four equations. In critically ill patients with sepsis, BMI was a better predictor of in-hospital mortality than the lean body mass equation at intensive care unit (ICU) admission. To precisely predict in-hospital mortality, ICU-specific lean body mass equations are needed. Full article