Diseases, Volume 11, Issue 3 (September 2023) – 36 articles

Background: tixagevimab/cilgavimab, distributed under the name “Evusheld”, was the first available pre-exposure prophylaxis for COVID-19 other than vaccination. It received an EUA from the FDA after sufficient trial data showed efficacy in preventing SARS-CoV-2 infections and subsequent severe disease. Its potential benefits for high-risk immunocompromised patients generated a lot of interest. Individuals with multiple myeloma fall into this category, as they are characterized by attenuated immune responses and, in some cases, vaccines have limited efficacy. Methods: this single-center, prospective study included consecutive patients with multiple myeloma. All individuals were considered high-risk for COVID-19 due to their underlying disease. Baseline demographic and clinical characteristics, as well as data regarding COVID-19 infection and antibodies, were collected. Patients were administered two intramuscular 150 mg doses of Evusheld and were monitored during the follow-up period. Results: one hundred and eleven multiple myeloma patients were included in this analysis, with a median age of 64 years (range 58–69) and fifty-three were females (47.7%). Fourteen patients (12.6%) had a prior history of COVID-19 and all patients were vaccinated with either three or four doses of mRNA-based vaccines. An increase was observed in the median neutralizing-antibody levels before and after tixagevimab/cilgavimab administration, from 92.6% to 97.3%. The high levels were sustainable, with a median neutralizing-antibody level of 95.4% at 3 months post Evusheld administration. Overall, nine patients (8.1%) were diagnosed with COVID-19 during the follow-up period, at a median of 31 days. There were no SARS-CoV-2- infection-related hospitalizations or deaths. The monoclonal antibody combination was well tolerated, with no infusion-related reactions or major adverse events, and pain at the injection site only was reported by 33 patients (30%). Conclusions: tixagevimab/cilgavimab (Evusheld) seemed beneficial for patients with multiple myeloma, who presented high neutralizing-antibody levels and a low incidence of COVID-19 during the initial Omicron wave. No new safety concerns emerged. However, novel combinations of monoclonal antibodies against the new circulating variants of SARS-CoV-2 are deemed necessary in view of the emergence of immune tolerance. Full article

Respiratory infections constitute a major reason for infants and children seeking medical advice and visiting health facilities, thus remaining a significant public threat with high morbidity and mortality. The predominant viruses causing viral respiratory infections are influenza A and B viruses (Flu-A, Flu-B), respiratory syncytial virus (RSV), adenovirus and coronaviruses. We aimed to record the proportion of RSV, SARS-CoV-2, influenza A/B and adenovirus cases with rapid antigen tests and validate the results with RT-PCR assays of upper respiratory specimens with a wide range of viral loads and (co)-infection patterns in children. Clinical samples were collected from early symptomatic children (presenting with fever and/or cough and/or headache within 5–7 days). The surveillance program was conducted in five private pediatric dispensaries and one pediatric care unit, from 10 January 2023 to 30 March 2023 in central Greece. The total sample of specimens collected was 784 young children and infants, of which 383 (48.8%) were female and 401 were male (51.2%). The mean age of participants was 7.3 + 5.5 years. The sensitivity of the FLU A & B test was 91.15% (95% CI: 84.33–95.67%), and the specificity was 98.96% (95% CI: 97.86–99.58%). The sensitivity and specificity of the adenovirus and RSV test was {92.45% (95% CI: 81.79–97.91%), 99.32% (95% CI: 98.41–99.78%)} and {92.59% (95% CI: 75.71–99.09%), 99.47% (95% CI: 98.65–99.86%)} respectively. Lastly, the sensitivity of the SARS-CoV-2 test was 100.00% (95% CI: 79.41–100.00%) and the specificity was 99.74% (95% CI: 99.06–99.97%). We recorded a proportion of 14.3% and 3.44% for influenza A and B, respectively, followed by a proportion of 6.9% for adenovirus, a proportion of 3.7% for RSV, and finally, a proportion of 2.3% for SARS-CoV-2. The combination of a new multiple rapid test with multiple antigens will probably be a useful tool with a financial impact for health systems targeting the early detection and appropriate treatment of respiratory infections in emergency departments in primary health care facilities. Full article

Background: In recent years, several interesting case reports have been published which describe the possible role of SARS-CoV-2 infection or vaccination in the etiopathogenesis of Lipschütz ulcer. Our aim is to analyze this association and provide a rapid algorithm that is of support to gynecologists and dermatologists both in the diagnosis and in setting up the therapy. To do so, in this paper, we describe an interesting case of acute vulvar ulcer triggered by SARS-CoV-2 infection and review the related literature. Methods: We conducted a literature review including papers published between October 2021 and April 2023, and we described the case of a patient referred to our clinic with Lipschütz ulcer and SARS-CoV-2 infection. Results: In almost all cases analyzed, a correlation with SARS-CoV-2 infection or vaccination was found; ulcers usually manifest after 2 to 4 weeks and are associated with flu-like symptoms. A concordance in review papers, as well as in our case report, was also found about the treatment, which is mainly symptomatic. Conclusions: Previous infection or vaccination for SARS-CoV-2 should be included as possible etiopathogenetic factors in the onset of Lipschütz ulcer. Full article

Background: Loss of muscle mass, and its strength, is associated with adverse outcomes in many medical and surgical conditions. Trauma patients may get malnourished during their hospital course due to many interrelated contributing factors. However, there is insufficient knowledge on the acute muscle and fat changes in young trauma patients in the early days post-admission. Objective: to explore the diagnosis, feeding status, and outcome of muscle mass loss among young abdominal polytrauma patients. Methods: It was a retrospective study including hospitalized abdominal trauma patients who underwent an abdominal computerized tomographic (CT) examination initially and a follow-up one week later. CT scan-based automatic and manual analysis of the muscles and fat of the abdominal region was calculated and compared. Also, we evaluated the feeding and nutritional values to explore the adequacy of the provided calories and proteins and the potential influence of enteral feeding on the CT-based parameters for muscle loss and fat depletion. Results: There were 138 eligible subjects with a mean age of 32.8 ± 13.5 years; of them, 92% were males. Operative interventions were performed on two-thirds of the patients, including abdominal surgery (43%), orthopedic surgeries (34%), and neurosurgical procedures (8.1%). On admission, 56% received oral feeding, and this rate slightly increased to 58.4% after the first week. Enteral feed was prescribed for the remaining, except for two patients. The percentage of change in the total psoas muscle area was significantly reduced after one week of admission in patients on enteral feed as compared to those in the oral feeding group (p = 0.001). There were no statistically significant differences in the percentages of changes in the CT scan findings except for the total psoas muscle area (p = 0.001) and para-spinal muscle area (p = 0.02), which reduced significantly in the those who underwent laparotomy as compared to those who did not need laparotomy. Trauma patients who underwent emergency abdominal surgery lost muscle and fat over time. Conclusions: Loss of muscle mass and body fat is not uncommon among young trauma patients. Patients who underwent laparotomy are more likely to be affected. Further larger studies are needed to assess the specific features in the younger trauma population and how far this can be influenced by the nutrition status and its impact on the clinical outcomes. It could be early or impending stages of sarcopenia linked to trauma patients, or just acute changes in the muscle and fat, that need further investigation and follow-up after hospital discharge. Full article

In May 2023, the global health emergency status of COVID-19 concluded, marking the onset of an endemic era. This study assessed survival rates among PCR-confirmed adult inpatients during this phase and determined contributing factors. Employing a survival analysis approach, this investigation utilized a nationwide Mexican cohort encompassing 152 adult inpatients. Survival rates were computed using the Kaplan–Meier method, and a proportional Cox model identified mortality risk factors. Survival rates remained above 65% on day 14 after admission. Vaccination status, including the number of doses administered, was not significantly associated with fatal outcomes. Chronic kidney disease or a history of immunosuppression (due to any cause) increased mortality risk. Our findings underscore the persistent severity of COVID-19 beyond the global health emergency, emphasizing the necessity for tailored interventions for vulnerable patients. Full article

Larger-size primary tumors are correlated with axillary metastases and worse outcomes. We evaluated the relationships among tumor size, location, and distance to nipple relative to axillary node metastases in triple-negative breast cancer (TNBC) patients, as well as the predictive capacity of imaging. We conducted a single-institution, retrospective chart review of stage I–III TNBC patients diagnosed from 1998 to 2019 who underwent upfront surgery. Seventy-three patients had a mean tumor size of 20 mm (range 1–53 mm). All patients were clinically node negative. Thirty-two patients were sentinel lymph node positive, of whom 25 underwent axillary lymph node dissection. Larger tumor size was associated with positive nodes (p < 0.001): the mean tumor size was 14.30 mm in node negative patients and 27.31 mm in node positive patients. Tumor to nipple distance was shorter in node positive patients (51.0 mm) vs. node negative patients (73.3 mm) (p = 0.005). The presence of LVI was associated with nodal positivity (p < 0.001). Tumor quadrant was not associated with nodal metastasis. Ultrasound yielded the largest number of suspicious findings (21/49), with sensitivity of 0.25 and specificity of 0.40. On univariate analysis, age younger than 60 at diagnosis was also associated with nodal positivity (p < 0.002). Comparative analyses with other subtypes may identify biologic determinants. Full article

Background: Tricuspid annular plane systolic excursion (TAPSE) and tricuspid regurgitation velocity (TRV) are two echocardiographic parameters with prognostic value in patients with pulmonary hypertension (PH). When analyzed concurrently as the TRV/TAPSE ratio, they allow the ventricular–pulmonary artery coupling (RVPAC) to be assessed. This could better predict disease severity in patients with PH. Objective: Our study aimed to evaluate the prognostic value of the TRV/TAPSE ratio echocardiographic parameter in adults with precapillary PH. Methods: This study included 39 patients (74% women; average age, 63 years) with precapillary PH (pulmonary arterial hypertension and chronic thromboembolic PH) The mean follow-up period was 16.6 ± 13.3 months. Twelve patients (31%) died during the observation time. We measured TAPSE as a surrogate of RV contractility and TRV reflecting RV afterload, while ventricular–arterial coupling was evaluated by the ratio between these two parameters (TRV/TAPSE). To assess disease progression and the patient’s functional capacity, the World Health Organization functional class (WHO FC) was determined. Patient physical capacity was also evaluated using the 6 min walk test (6MWT). The analysis included values of N-terminal prohormone brain natriuretic peptide (NT-proBNP), which were taken routinely during the follow-up visit. Results: The mean calculated TRV/TAPSE ratio was 0.26 ± 0.08 m/s/mm. Upon comparison of the TRV/TAPSE ratio to the disease prognostic indicators, we observed a statistically significant correlation between TRV/TAPSE and the results of the WHO FC, 6MWT, and NT-proBNP. The TRV/TAPSE ratio is thus a good predictor of mortality in PH patients (AUC, 0.781). Patients with a TRV/TAPSE ratio > 0.30 m/s/mm had a shorter survival time, with log-rank test p < 0.0001. Additionally, ROC analysis revealed higher AUC for TRV/TAPSE than for TAPSE and TRV alone. Conclusions: TRV/TAPSE is a promising practicable echocardiographic parameter reflecting RVPAC. Moreover, TRV/TAPSE could be viable risk stratification parameter and could have prognostic value in patients with PH. Full article

Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990–2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of 30 years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut–brain and lung–brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both. Full article

Alpha synuclein (α-Syn) is a neuronal protein encoded by the SNCA gene and is involved in the development of Parkinson’s disease (PD). The objective of this study was to examine in silico the functional implications of non-synonymous single nucleotide polymorphisms (nsSNPs) in the SNCA gene. We used a range of computational algorithms such as sequence conservation, structural analysis, physicochemical properties, and machine learning. The sequence of the SNCA gene was analyzed, resulting in the mapping of 42,272 SNPs that are classified into different functional categories. A total of 177 nsSNPs were identified within the coding region; there were 20 variants that may influence the α-Syn protein structure and function. This identification was made by employing different analytical tools including SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, I-Mut, and HOPE. Three mutations, V82A, K80E, and E46K, were selected for further examinations due to their spatial positioning within the α-Syn as determined by PyMol. Results indicated that these mutations may affect the stability and function of α-Syn. Then, a molecular dynamics simulation was conducted for the SNCA wildtype and the four mutant variants (p.A18G, p.V82A, p.K80E, and p.E46K). The simulation examined temperature, pressure, density, root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration (Rg). The data indicate that the mutations p.V82A, p.K80E, and p.E46K reduce the stability and functionality of α-Syn. These findings highlight the importance of understanding the impact of nsSNPs on α-syn structure and function. Our results required verifications in further protein functional and case–control studies. After being verified these findings can be used in genetic testing for the early diagnosis of PD, the evaluation of the risk factors, and therapeutic approaches. Full article

Background: We herein report two cases of sudden onset symptomatic pulmonary hypertension after coronavirus disease 2019 (COVID-19) vaccination. Case Summary: Pulmonary hypertension in previously healthy adult males occurred within three weeks of receiving the second dose of the Pfizer (BNT162b2) mRNA COVID-19 vaccine from different lots. Both patients experienced a sudden onset of severe fatigue and dyspnea on exertion with negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing. The diagnosis was made by serial transthoracic echocardiography in the first case and by both transthoracic echocardiography and right heart catheterization in the second. Both cases resulted in functional limitations and likely permanent organ damage. No evidence of pulmonary emboli was detected in either case. Discussion: Pulmonary hypertension is a serious disease characterized by damage to lung vasculature and restricted blood flow through narrowed arteries from the right to left heart. The onset of symptoms is typically insidious, progressive and incurable, leading to right heart failure and premature death. The World Health Organization (WHO) classifies pulmonary hypertension into five categories and recently re-defined it as a resting mean pulmonary artery pressure greater than 20 mmHg. Sudden onset pulmonary hypertension would only be expected in the settings of surgical pneumonectomy or massive pulmonary emboli with compromise of at least 50% of the lung vasculature. We present here two novel cases of sudden onset pulmonary hypertension without evidence of pulmonary emboli, both of which occurred after receiving a COVID-19 mRNA vaccine. Full article

COVID-19 has generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and evaluation in the subsequent months showed improvement in the evolutionary image. With less than six months post-pathology, there was a commitment of 37.7% from six to twelve months it was 20%, and after 12 months it was 9.9%. As for most of the sample, 50.3% of the patients presented CT normalization less than six months after infection, 23% were normalized between six and twelve months, and 5.2% presented with normalized images after twelve months, with one remaining. A percentage of 17.3% maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, less than six months after pathology, 59.3% of the patients presented regular exam results, 12.3% had their function normalized within six to twelve months, and 6.3% had normal exam results twelve months after their post-pathology evaluation. Only 3.6% of the patients still showed some alteration during this period. Full article

Coronavirus disease 2019 (COVID-19) is a contagious illness worldwide. While guidelines for the treatment of COVID-19 have been established, the understanding of the relationship among neutralizing antibodies, cytokines, and the combined use of antiviral medications, steroid drugs, and convalescent plasma therapy remains limited. Here, we investigated the connection between the immunological response and the efficacy of convalescent plasma therapy in COVID-19 patients with moderate-to-severe pneumonia. The study included a retrospective analysis of 49 patients aged 35 to 57. We conducted clinical assessments to determine antibody levels, biochemical markers, and cytokine levels. Among the patients, 48 (98%) were discharged, while one died. We observed significantly higher levels of anti-nucleocapsid, anti-spike, and neutralizing antibodies on days 3, 7, and 14 after the transfusion compared to before treatment. Serum CRP and D-dimer levels varied significantly across these four time points. Moreover, convalescent plasma therapy demonstrated an immunoregulatory effect on cytokine parameters, with significant differences in IFN-β, IL-6, IL-10, and IFN-α levels observed at different sampling times. Evaluating the cytokine signature, along with standard clinical and laboratory parameters, may help to identify the onset of a cytokine storm in COVID-19 patients and determine the appropriate indication for anti-cytokine treatment. Full article

Background: Respiratory syncytial virus (RSV) is one of the most frequent etiological factors of lower respiratory tract infections in children, potentially affecting patients’ quality of life (QoL). We aimed to asses QoL in children under 2 years of age hospitalized due to laboratory-confirmed RSV infection. Methods: A QoL was assessed by parents/tutors with the use of the 100-point visual analog scale and compared against a disease-free period. We evaluated the median utility, QoL loss (reported in days), and quality-adjusted life years (QALY) loss in relation to RSV hospitalization. Results: We included 132 patients aged from 17 days to 24 months (median 3.8 months). The mean utility during the hospitalization varied between 0.418 and 0.952, with a median of 0.679 (95%CI: 0.6–0.757) and median loss of 0.321 [0.243–0.4], which further translated into a loss of 2.2 days (95%CI: 1.6–3.1). The QALY loss varied between 0.526 × 10⁻³ and 24.658 × 10⁻³, with a median of 6.03 × 10⁻³ (95%CI: 4.38–8.48 × 10⁻³). Based upon the final diagnoses, the highest QALY loss was 6.99 × 10⁻³ (95%CI: 5.29–13.7 × 10⁻³) for pneumonia, followed by bronchiolitis—5.96 × 10⁻³ (4.25–8.41 × 10⁻³) and bronchitis—4.92 × 10⁻³ (2.93–6.03 × 10⁻³); significant differences were observed only between bronchitis and pneumonia (p = 0.0171); the QALY loss was not age-dependent. Although an increasing tendency in the utility score was observed, a strong cumulative effect related to the length of stay was noted until day 13. Conclusions: RSV contributes significantly to the utility deterioration and QALY loss in the case of RSV hospitalization, and the patient-reported data should be used in pharmacoeconomic assessments of the impact of RSV. Full article

The aim of this study was to evaluate a potential correlation between results of the oral glucose tolerance test (OGTT) and the auxological/metabolic parameters in a cohort of overweight patients assessed for suspicion of hyperinsulinism. We analyzed 206 patients, comparing those with insulin peak below (nonhyperinsulinemic) and over 100 uIU/mL (hyperinsulinemic) at the OGTT. We found a significant difference in weight (p = 0.037), body mass index (BMI, p < 0.001) and BMI standard deviations (SD, p < 0.001), waist circumference (p = 0.001), hip circumference (p = 0.001), and waist-to-height ratio (WHtR, p = 0.016) between the two groups. Analyzing the median insulin value during OGTT in the whole population, a weakly positive correlation emerged with weight SD (p < 0.001; rho = 0.292) and a moderate positive correlation with BMI SD (p < 0.001; rho = 0.323). We also found a weakly positive correlation with waist circumference (p = 0.001; rho = 0.214), hip circumference (p = 0.001; rho = 0.217), and WHTR (p = 0.016; rho = 0.209) and a moderate positive correlation with the HOMA index (p < 0.001; rho = 0.683). The median insulin value correlates with high triglyceride (p < 0.001; rho = 0.266) and triiodothyronine values (p = 0.003; rho = 0.193) and with low HDL values (p < 0.001; rho = −0.272). In clinical practice the interpretation of laboratory and anthropometric parameters could predict the level of insulin, highlighting also a possible underlying diagnosis of insulin resistance and/or hyperinsulinemia without performing an OGTT. Full article

The aim of this review is to determine the safety and efficacy of pre-operative spinal metastases embolization procedures. Two reviewers independently conducted the literature search (on MEDLINE databases), including in the review of all the studies that used pre-operative TAE to treat spinal metastases. Twelve articles on pre-operative spinal metastases embolization were selected. Most of the studies demonstrated the low complication rate of pre-operative embolization. The most important study strength is that there are very few reviews in the literature with the setting on pre-operative vertebral metastases embolization. A limitation of the review is that the studies included were predominately retrospective case-control studies, increasing the risk of bias in the primary data. Plus, divergent surgical and embolization procedures were performed in the studies, causing a potential risk of bias in the pooled results. We can conclude that preoperative arterial embolization of vertebral metastases is a safe, well-tolerated technique that reduces surgical blood loss and facilitates surgical tumor resection. Full article

An aneurysmal fibrous histiocytoma is a rare cutaneous soft-tissue tumour which accounts for approximately 0.06% of all dermatopathologies. Metastasis is exceedingly uncommon, to the point that there have only been eight reported cases in the scientific literature. We present the case of a 25-year-old male with a primary aneurysmal fibrous histiocytoma located in the nuchal region which exhibited rapid growth and abrupt ulceration over a short time span and showed signs of locoregional aggressive infiltration. A subsequent histopathological analysis confirmed the presence of diffuse solid and cystic pulmonary metastases. Further genetic sequencing verified LAMTOR1-PRKCD fusion. This case report seeks to review the existing literature on aneurysmal fibrous histiocytoma, discuss the challenges of differential diagnosis and propose standardised diagnostic criteria. Full article

Background: Traumatic spinal cord injury (SCI) is a neurological disorder that causes a traumatic anatomical discontinuity of the spinal cord. SCI can lead to paraplegia, spastic, or motor impairments. Go-karting for people with SCI is an adapted sport that is becoming increasingly popular. The purpose of this case report is to shed light on the effects of driving a go-kart on a patient with SCI-related spasticity and to deepen understanding of the possible related role of whole-body vibration (WBV) and neuroendocrine reaction. Methods: The patient was a 50-year-old male with a spastic paraplegia due to traumatic SCI. He regularly practiced go-kart racing, reporting a transient reduction in spasticity. He was evaluated before (T0), immediately after (T1), 2 weeks after (T2), and 4 weeks after (T3) a go-kart driving session. On both sides, long adductor, femoral bicep, and medial and lateral gastrocnemius spasticity was assessed using the Modified Ashworth Scale (MAS), and tone and stiffness were assessed using MyotonPro. Results: It was observed that a go-kart driving session could reduce muscle spasticity, tone, and stiffness. Conclusions: Go-kart driving can be a valid tool to obtain results similar to those of WBV and hormone production in the reduction of spasticity. Full article

Diabetes mellitus (DM) is one of the world’s most important health problems, affecting more than half a billion of the world’s population today, with an ever-increasing prevalence. Among the most common manifestations of diabetes are skin manifestations, with 30–70% of patients experiencing skin complications during the course of the disease. Conditions such as acanthosis nigricans, diabetic dermopathy, necrobiosis lipoidica, bacterial infections, fungal infections, skin xerosis, and metabolic prurigo are often associated with diabetes and often precede its diagnosis. We conducted a retrospective study on a group of 103 patients hospitalized between January 2018 and December 2022, in a clinic of a county hospital, using as criteria the diagnosis of diabetes mellitus complicated by cutaneous manifestations frequently associated with diabetes. The aim was to observe which are the most common manifestations and whether they correlate with data in the research literature. In the present study, manifestations such as diabetic foot (20% of patients), bacterial (35%) and fungal infections, and cutaneous xerosis (45%) were predominant. Often, the integumentary involvement may precede the diagnosis of the underlying disease. It is therefore very important to recognize, investigate and treat these manifestations as soon as possible. Full article

Introduction: The need for effective therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remained largely unmet. Previous work has shown that a combination of three aromatic plants’ essential oils (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticose Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care settings. Methods: A total of 69 adult patients were included in a clinical proof-of-concept (PoC) intervention study. Family physicians implemented the observational study in two arms (intervention group and control group) during three study periods (IG_{2020, n=13}, IG_{2021/22, n=25}, and CG_{2021/22, n=31}). The SARS-CoV-2 infection was confirmed by real-time PCR. The CAPeo mixture was administered daily for 14 days per os in the intervention group, while the control group received usual care. Results: The PoC study found that the number and frequency of general symptoms, including general fatigue, weakness, fever, and myalgia, decreased following CAPeo administration. By Day 7, the average presence (number) of symptoms decreased in comparison with Day 1 in IG (4.7 to 1.4) as well as in CG (4.0 to 3.1), representing a significant decrease in the cumulative presence in IC (−3.3 vs. −0.9, p < 0.001; η² = 0.20) on Day 7 and on Day 14 (−4.2 vs. −2.9, p = 0.027; η² = 0.08). Discussion/Conclusions: Our findings suggest that CAPeo possesses potent antiviral activity against SARS-CoV-2 in addition tο its effect against influenza A and B and human rhinovirus HRV14 strains. The early and effective impact on alleviating key symptoms of COVID-19 may suggest this mixture can act as a complementary natural agent for patients with mild COVID-19. Full article

Childhood respiratory tract infections (RTIs) pose a significant health burden, especially in children under six years old. The main objective of this systematic review was to assess the effectiveness of vitamin D supplementation in the prevention of RTI in this population while also exploring potential effect modifiers such as age, baseline vitamin D status, and type of respiratory infection. A systematic review of the literature published up to February 2023 was conducted according to PRISMA guidelines, searching PubMed, Web of Science, Cochrane, and Scopus databases. Eight studies met the inclusion criteria, which investigated the association between vitamin D supplementation and respiratory infections in children between zero and five years old. The included studies were conducted between 2012 and 2021, encompassing a total of 2189 children from five randomized trials, two case-control studies, and one prospective cohort study. The relationship between vitamin D supplementation and the prevention of childhood RTI was not consistently observed across all included studies. Pooled results demonstrated varied effects of vitamin D supplementation on respiratory infection incidence, severity, and symptoms. Three studies reported statistically significant associations between low vitamin D levels and respiratory infections (OR = 4.90, OR = 6.97), while one study found that children who received vitamin D supplementation of 800 UI/day for 3 months during the cold season had fewer episodes of respiratory symptoms (RR = 0.55) and recovered more quickly from acute RTI. Lastly, according to one study, vitamin D intake < 80 IU/kg/day was significantly associated with the risk of acquiring pneumonia (OR 7.9) but not bronchiolitis. The remaining five studies found no statistically significant differences in infection rates or severity (p-value > 0.050). The available evidence on the effectiveness of vitamin D supplementation for preventing and treating respiratory infections in children under six years old is limited, with only a few favorable effects being reported. In some cases, a dose of 80 UI/kg/day was found to provide significant protection for acute respiratory infections, although in the major trials the only benefit was a quicker recovery and fewer respiratory symptoms, with no impact on incidence and severity of respiratory infections. Nevertheless, the study protocol, the supplementation dose, and duration of supplementation had significant variations between studies, leading to inconclusive findings. Full article

Background: There is significant pathogenic and epidemiological overlap between diabetes and obstructive sleep apnea (OSA). This systematic review aimed to ascertain the association between OSA and cardiovascular disease (CVD) in a diabetic population. Methods: The study protocol was registered with PROSPERO (CRD42023404126). On 15 July 2023, a comprehensive search of the literature was performed in PubMed, EBSCO, Scopus, ProQuest, and Web of Science, using keywords and synonyms of OSA, diabetes, and CVD, coupled with specific terms for different CVDs. Only observational studies that reported CVD events in diabetics (with and without OSA) were included. The quality of the studies included in the analysis was assessed using the Newcastle–Ottawa Scale. Results: In the primary literature search, 8795 studies were identified, of which 9 met the inclusion criteria and included 17,796 participants. Eight studies were eligible for meta-analysis, and a pooled risk ratio (RR) of 1.29 (95% CI = 0.91–1.83) was found for developing CVD in diabetics with OSA at a 95% prediction interval of 0.30–5.60. The included studies showed significant heterogeneity with an I² value of 91%. Conclusion: These findings show the possible association between OSA and diabetes and their impact on CVDs. Identifying and managing OSA in individuals with diabetes at an early phase could potentially reduce the risk of CVDs and its related complications. Full article

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had significant impacts on pulmonary function. This study aimed to comprehensively evaluate pulmonary function and structure in patients 40 days post-SARS-CoV-2 infection, employing an array of testing methodologies including spirometry, plethysmography, forced oscillometry, and CT scanning. It also sought to establish potential correlations between these metrics and evaluate if forced oscillometry could provide additional value in post-infective lung function assessment. A 40-day post-infection follow-up observational study was conducted involving 66 patients with confirmed SARS-CoV-2 infection. The results revealed decreases in FVC and FEF25–75 with the increasing severity of COVID-19. Specifically, patients with severe symptoms exhibited statistically significant decreases in FVC (mean = 86.8) compared with those with mild symptoms (mean = 106.0; p = 0.018). The FEF25–75 showed a similar trend, with severe patients exhibiting a mean of 77.7 compared with 82.9 in the mild group (p = 0.017). Furthermore, resonant frequency (RF) increased with disease severity, with the severe group exhibiting a statistically significant increase (mean = 17.4) compared with the mild group (mean = 14.3; p = 0.042). CT scans showed an increase in ground-glass opacities with disease severity, with 81.8% of severe patients demonstrating this finding (p = 0.037). Multiple regression analysis revealed that Reactance at 4 Hz (X4), Forced Expiratory Flow 25–75% (FEF25–75), and Resonant Frequency (RF) were significantly related to COVID-19 severity. Specifically, for each unit increase in these factors, the risk of the event was estimated to increase by a factor of 3.16, 2.09, and 1.90, respectively. Conversely, Resistance at 4 Hz (R4) and Airway Resistance (RAW) were found to significantly decrease the event hazard, highlighting their potential protective role. Spirometry, plethysmography, and forced oscillometry are effective in assessing these changes. Forced oscillometry may be particularly beneficial in identifying subtle changes in lung function post-COVID-19. Further studies are warranted to validate these findings and develop strategies to manage post-infective pulmonary changes in SARS-CoV-2 patients. Full article

Background: Cytomegalovirus (CMV) is a highly prevalent virus with a worldwide distribution. It typically remains dormant in most individuals until reactivation. Immunocompromised states are known to be potential causes for CMV reactivation. Current research has shown a link in the decline of immigrant health among those living in the US for an extended period, though the impact of CMV on this is not clear. Methods: This study investigated the association between country of birth, duration of US residency, allostatic load, and latent cytomegalovirus infection (CMV IgG) in a sample of US adults aged 20–49. The data utilized for our analysis was obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Allostatic load, an index measuring the cumulative physiological strain on the body as it strives to regain stability in the presence of chronic stress, provided a valuable approach to assess stress within the context of CMV exposure. Logistic regression modeling was employed to estimate odds ratios and confidence intervals for the analysis. The chi-square test of association and Cramer’s V statistic were used to assess the correlation among categorical variables, while Pearson’s correlation coefficient was applied to evaluate the relationship between continuous variables. The results revealed that individuals born outside the US and those with less than 20 years of residency in the US exhibited significantly higher proportions of positive CMV IgG compared to individuals born in the US. Specifically, individuals born outside the US had more than triple the odds of CMV IgG when adjusting for the AL index (OR = 3.69, p-value = 0.0063). A similar trend was observed when examining AL risk based on the duration of US residency. Furthermore, age and sex were identified as significant predictors (p-value < 0.05) of AL risk, considering the individual’s country of birth. In summary, the findings of this study significantly enhance our comprehension of the intricate interplay between cytomegalovirus (CMV) and allostatic load (AL). The investigation sheds light on how CMV and AL interact within specific demographic contexts, providing valuable insights into the underlying risk factors for CMV infection. Full article

Introduction: Conduction disorders following aortic valve replacement therapy (AVR), either surgical or percutaneous, are related to a higher risk of complete atrioventricular block and permanent pacemaker implantation (PPI). Aim: The objective of this study was to assess risk factors regarding the incidence of new postoperative and persistent new left bundle branch block (LBBB) 1 year after the implantation of a sutureless/rapid-deployment (SURD) aortic valve prosthesis. Material and Methods: The current study included 200 consecutive patients treated with isolated or concomitant AVR between May 2014 and May 2017 at the Department of Cardiac Surgery in Pasawa with SURD aortic valve EDWARDS INTUITY Elite^TM implantation. The patients were divided according to the presence of new postoperative LBBB (67 patients, 33.5%) and persistent new LBBB 1 year after AVR (35 patients, 17.5%). A comparative analysis was performed between patients with and without new LBBB after AVR and those with and without persistent LBBB 1 year after AVR. Univariate and multivariate regression analyses were conducted to extract the risk factors of LBBB occurrence. Results: Among the risk factors for the lack of new LBBB development after AVR, Euroscore II (p < 0.001) was found, while for the occurrence of persistent new LBBB 1 year after AVR, atrial fibrillation (p = 0.001), length of hospital stay (p = 0.001) and body mass index (p = 0.004) were noted. Conclusions: Patients with new or persistent new LBBB 1 year after AVR had lower mean Euroscore II and BMI values. Their stay at the hospital was also shorter. Full article

Objectives: to analyse the clinical–pathological characteristics, treatment, and evolution of uterine smooth muscle tumours with uncertain malignant potential (STUMP) diagnosed in the Salamanca University Hospital with the implementation of the 2014 WHO criteria. Materials and methods: a retrospective descriptive study of patients diagnosed with STUMP from January 2015 to March 2023 at the Salamanca University Hospital. Demographic data, preoperative clinical data, treatment, complications, therapeutic results, anatomopathological findings and recurrence time were obtained. Results: a total of four patients were identified and included in the study. The mean age at diagnosis was 48 years (range 36–67). The surgical indications were abnormal uterine bleeding, compressive symptoms, and the growth of a pelvic mass suspected to be a degenerated myoma from the residual cervix after a subtotal hysterectomy 6 years earlier. In all cases, a laparotomic procedure was performed. A total hysterectomy, sub-total hysterectomy, and the excision of the cervix with STUMP localization were accomplished in two, one, and one patient, respectively. The mean diameter of the tumour pieces was 13 cm (range 8–17 cm), with a mean volume of 816 cc (range 234–1467 cc). The mean follow-up was 47 months, with no recurrence to date. Conclusions: STUMPs are a heterogeneous group of tumours with a difficult-to-predict clinical evolution. In most cases, their diagnosis is histological after performing surgery for suspected leiomyoma. Due to their low incidence, there are no specific guidelines for their treatment and control. However, considering their potential risk of recurrence and metastasis, it is advisable to maintain six-monthly controls for 5 years and then annual controls for 5 years more. Full article

Contact force (CF) is a novel approach developed to increase the safety and efficacy of catheter ablation. However, the value of CF-sensing technology for atrial flutter (AFL) cavo-tricuspid isthmus ablation (CTIA) is inconclusive. To generate a comprehensive assessment of optimal extant data on CF for AFL, we synthesized randomized controlled trials (RCTs) and observational studies from Web of Science, SCOPUS, EMBASE, PubMed, and Cochrane until 29 November 2022, using the odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with a corresponding 95% confidence interval (CI). Two RCTs and three observational studies with a total of 376 patients were included in our analysis. CF-guided ablation was associated with (A) a higher rate of AFL recurrence (OR: 2.26 with 95% CI [1.05, 4.87]) and total CF (MD: 2.71 with 95% CI [1.28, 4.13]); (B) no effect on total procedure duration (MD: −2.88 with 95% CI [−7.48, 1.72]), fluoroscopy duration (MD: −0.96 with 95% CI [−2.24, 0.31]), and bidirectional isthmus block (BDIB) (OR: 1.50 with 95% CI [0.72, 3.11]); and (C) decreased radiofrequency (RF) duration (MD: −1.40 with 95% CI [−2.39, −0.41]). We conclude that although CF-guided CTIA was associated with increased AFL recurrence and total CF and reduced RF duration, it did not affect total procedure duration, fluoroscopy duration, or BDIB. Thus, CF-guided CTIA may not be the optimal intervention for AFL. These findings indicate the need for (A) providers to balance the benefits and risks of CF when utilizing precision medicine to develop treatment plans for individuals with AFL and (B) clinical trials investigating CF-guided catheter ablation for AFL to provide definitive evidence of optimal CF-sensing technology. Full article

In the last decade, artificial intelligence (AI) and AI-mediated technologies have undergone rapid evolution in healthcare and medicine, from apps to computer software able to analyze medical images, robotic surgery and advanced data storage system. The main aim of the present commentary is to briefly describe the evolution of AI and its applications in healthcare, particularly in nutrition and clinical biochemistry. Indeed, AI is revealing itself to be an important tool in clinical nutrition by using telematic means to self-monitor various health metrics, including blood glucose levels, body weight, heart rate, fat percentage, blood pressure, activity tracking and calorie intake trackers. In particular, the application of the most common digital technologies used in the field of nutrition as well as the employment of AI in the management of diabetes and obesity, two of the most common nutrition-related pathologies worldwide, will be presented. Full article

Decades ago, the treatment for acute myeloid leukemia relied on cytarabine and anthracycline. However, advancements in medical research have introduced targeted therapies, initially employing monoclonal antibodies such as ant-CD52 and anti-CD123, and subsequently utilizing specific inhibitors that target molecular mutations like anti-IDH1, IDH2, or FLT3. The challenge lies in determining the role of these therapeutic options, considering the inherent tumor heterogeneity associated with leukemia diagnosis and the clonal drift that this type of tumor can undergo. Targeted drugs necessitate an examination of various therapeutic targets at the individual cell level rather than assessing the entire population. It is crucial to differentiate between the prognostic value and therapeutic potential of a specific molecular target, depending on whether it is found in a terminally differentiated cell with limited proliferative potential or a stem cell with robust capabilities for both proliferation and self-renewal. However, this cell-by-cell analysis is accompanied by several challenges. Firstly, the scientific aspect poses difficulties in comparing different single cell analysis experiments despite efforts to standardize the results through various techniques. Secondly, there are practical obstacles as each individual cell experiment incurs significant financial costs and consumes a substantial amount of time. A viable solution lies in the ability to process multiple samples simultaneously, which is a distinctive feature of the cell hashing technique. In this study, we demonstrate the applicability of the cell hashing technique for analyzing acute myeloid leukemia cells. By comparing it to standard single cell analysis, we establish a strong correlation in various parameters such as quality control, gene expression, and the analysis of leukemic blast markers in patients. Consequently, this technique holds the potential to become an integral part of the biological assessment of acute myeloid leukemia, contributing to the personalized and optimized management of the disease, particularly in the context of employing targeted therapies. Full article

Taeniasis is a neglected zoonotic disease responsible for serious health disorders, such as seizures, and may even cause death. Humans are the definitive host for the three species Taenia solium (pork tapeworm), T. saginata (beef tapeworm), and T. asiatica, harboring the adult tapeworm in the small intestine. In this study, a structured questionnaire was circulated to assess the knowledge, attitudes, and practices (KAPs) regarding taeniasis among the rural and urban communities of Rawalpindi and Islamabad, Pakistan. A total of 770 individuals participated in the study. Of the total respondents, 44.4% had little knowledge about the disease and its impact, while the majority (70%) of respondents showed a willingness to participate in elimination campaigns by providing fecal samples. Most respondents kept raw meat separated from clean utensils (81.6%) and checked the internal temperature of meat when cooking it (75.1%). Regression analysis showed a significant association between age and knowledge, especially in the 20–30 years (p < 0.05; OR 0.574) and 30 to 40 years (p < 0.05; OR 0.553) age groups, and being a resident in Rawalpindi (p < 0.05; OR 0.68) and other cities (p < 0.05; OR 2.43), except Islamabad. Income ranges of 31,000–50,000 PKR (p < 0.05; OR: 0.574), 51,000–70,000 PKR (p < 0.05; OR 0.531), and above 70,000 PKR (p < 0.05; OR 0.42) were significantly related to attitude, compared with individuals with incomes of 10,000–30,000 PKR. Income above 70,000 PKR (p < 0.05; OR 0.87) and living in an urban area (p < 0.05; OR 0.616) compared to a rural area were significant with practices. A positive attitude was observed regarding awareness and prevention of the disease. Awareness campaigns and providing health education could be key approaches to manage this disease in the general population of developing countries. Full article

Plasmodium falciparum (P. falciparum) and hepatitis B virus (HBV) co-infection is on the rise among pregnant women in northern Ghana. Mono-infection with either of these two pathogens results in unique metabolic alterations. Thus, we aimed to explicate the effects of this co-infection on the metabolome signatures of pregnant women, which would indicate the impacted metabolic pathways and provide useful prognostic or diagnostic markers. Using an MS/MS-based targeted metabolomic approach, we determined the serum metabolome in pregnant women with P. falciparum mono-infection, HBV mono-infection, P. falciparum, and HBV co-infection and in uninfected (control) women. We observed significantly decreased sphingolipid concentrations in subjects with P. falciparum mono-infection, whereas amino acids and phospholipids were decreased in subjects with HBV mono-infection. Co-infections were found to be characterized distinctively by reduced concentrations of phospholipids and hexoses (mostly glucose) as well as altered pathways that contribute to redox homeostasis. Overall, PC ae C40:1 was found to be a good discriminatory metabolite for the co-infection group. PC ae C40:1 can further be explored for use in the diagnosis and treatment of malaria and chronic hepatitis B co-morbidity as well as to distinguish co-infections from cases of mono-infections. Full article