Diseases, Volume 10, Issue 1 (March 2022) – 17 articles

Rabies is a zoonotic disease caused by the rabies virus (RABV) that causes fatal encephalitis in mammals. Bats can transmit the disease to urban canines and felines, which rarely infect humans, establishing a secondary link. The last case of human rabies in Argentina was transmitted by a dog in 2008. We present the first case of human rabies originating from an insectivorous bat, Tadarida brasiliensis, transmitted by a feral cat in Buenos Aires province, Argentina. Full article

Aim: The impact of chronic kidney disease (CKD) on patient-related outcomes in patients with tricuspid regurgitation (TR) is well known. However, the impact of the progression of CKD in patients with TR and potentially modifiable risk factors of progressing CKD is unknown. Methods: 444 consecutive adult patients with TR and CKD stage 1–4 admitted in an inpatient setting between January 2010 and December 2017 were included. During a median follow-up of two years, eGFR and survival status were collected. Independent risk factors for CKD progression and all-cause mortality were determined. Patient survival statuses were grouped according to different combinations of the presence or absence of CKD progression and the TR grade. Results: Progression of CKD (OR 2.38 (95% confidence interval 1.30–4.35), p = 0.005), the grade of TR (OR 2.38 (1.41–4.00), p = 0.001) and mitral regurgitation (OR 1.72 (1.20–2.46), p = 0.003) were independent risk factors for all-cause mortality. Haemoglobin at admission (OR 0.80 (0.65–0.99), p = 0.043) and the presence of type 2 diabetes (OR 1.67 (1.02–2.73), p = 0.042) were independent risk factors for CKD progression. The combination of the status of CKD progression and the TR grade showed a stepwise pattern for all-cause mortality (p < 0.001). Patients with CKD progression and TR grade 1 had comparable all-cause mortality with patients without CKD progression but with TR grade 2 or 3. Even in patients with TR grade 1, the risk for all-cause mortality doubled if CKD progression occurred (OR 2.49 (95% CI 1.38–4.47), p = 0.002). Conclusion: CKD progression appears to be a risk factor for all-cause mortality in patients with TR. Anaemia and diabetes are potential modifiers of CKD progression. Full article

Type 2 Diabetes Mellitus (T2DM) is a complicated multifactorial illness involving hereditary and external environmental variables. The symptoms typically appear gradually over a number of years without realizing it. This viewpoint is further supported by the Ayurvedic constitution concept (Prakriti). Prakriti explains the biological variability that is observed in different individuals. This study was conducted a retrospective investigation to examine if there was a link between type 2 diabetes and an individual’s constitution based on anthropometric and biochemical characteristics. Physical and mental characteristics and anthropometric and biochemical markers were used to determine reported cases’ prevailing Dosha Prakriti (constitution). Based on biochemical and anthropometric data, significant differences in Prakriti were found between the case (T2DM patients) and control (person without diabetes) groups. The incidence of numerous secondary problems linked with T2DM patients was also evaluated according to their Prakriti types, which revealed a positive relationship. The three primary contributing parameters, such as waist-hip ratio, postprandial blood sugar, and serum creatinine, were correctly classified all person with or without diabetes subjects to 90.6% of the time, whereas the constitution-wise study classified person with diabetes and without diabetes individuals of Pitta and Kapha Prakriti to 94.3% and 90%, respectively. A discriminant function was created to predict a person with diabetes and without diabetes based on these three contributing factors. The primary contributing biochemical parameters discovered by Prakriti in the current study could be used as a biochemical disease diagnostic for predicting type 2 diabetes susceptibility. Full article

Inflammatory bowel diseases (IBD) are systemic conditions characterized by multiple intestinal and extra-intestinal manifestations related to the associated chronic inflammatory state. Among their diverse extra-intestinal complications, venous thromboembolism (VTE) remains one of the most under recognized causes of morbidity and mortality in these patients, highlighting the need for a better understanding of the underlying mechanism of hypercoagulability, in addition to the role of acquired and inherited risk factors that further increase the risk of thrombosis with its impact on patients’ outcomes. We hereby present a review of the data regarding thrombosis in the setting of IBD, elucidating the possible role for screening in this high-risk category of patients and specifically in areas where inherited thrombophilia is expected to be highly prevalent, reporting two patients with IBD, one who developed a cerebrovascular event and another one who had recurrent VTE events; nevertheless, both of them had inherited thrombophilic mutations. The identification of specific genetic abnormalities in those patients reintroduces the controversy related to the need to screen a specific category of patients with IBD for hereditary thrombophilia, especially in regions characterized by a higher prevalence of such thrombophilic alterations. Full article

New advancements in the medical community have rapidly occurred with the development of medical information across the globe during the COVID-19 pandemic. Several vaccine manufacturers were able to obtain clearance to administer vaccines in selected age groups and for those at high risk for COVID-19 complications. As vaccines became more readily available, there was a significant effort supported by scientific information to get people vaccinated to boost herd immunity. Acute demyelinating encephalomyelitis (ADEM) is a rare autoimmune disease, causing demyelination in the brain and spinal cord, presenting as monophasic, acute-onset, and rapidly progressive multifocal neurological deficits. A wide variety of precipitating factors can trigger ADEM, and it has long been known to be a rare adverse event following some types of vaccinations including rabies, diphtheria–tetanus–polio, smallpox, measles, mumps, rubella, pertussis, influenza, and hepatitis B vaccines. Recently, ADEM has also been associated with COVID-19 infection and (very rarely) with COVID-19 vaccination. We have a 56-year-old female who was not known to have any medical issues. She voluntarily received her first COVID-19 vaccination (AstraZeneca) ten days after immunization; she developed weakness of the lower limbs and slurred speech. She tested negative for COVID-19, and a brain MRI showed T2-weighted white-matter hyperintense lesions suggesting acute demyelinating encephalomyelitis. She was managed with pulse-dose steroids, which resulted in a marked improvement in her symptoms, and discharged in a stable condition. Physicians should be aware of this neurological disorder and the management options for better patient care and outcomes. Full article

Introduction: Periodontitis is the most prevalent inflammatory disease worldwide. Its inflammatory levels spread systemically, which can be associated with chronic kidney disease. Biomarkers have the potential to diagnose and correlate periodontitis and chronic kidney disease, helping to monitor systemic inflammation. Thereby, this study aimed to analyze the association between chronic kidney disease and periodontitis by conducting a biomarker analysis on blood and saliva. Material and methods: An electronic search through PubMed/MEDLINE, EMBASE, and Web of Science databases was conducted to identify clinical studies published in the last ten years, with no language restrictions. Twelve articles met all the inclusion criteria, two randomized controlled trials, one cohort study, and nine observational studies. Results: The studies included a total of 117 patients for saliva biomarkers, with a mean age of approximately 57 years old, and 56.68% of the subjects were female. After analyzing all the included studies, it was possible to verify the following biomarkers assessed: CRP, WBC, fibrinogen, IL-4 and -6, cardiac troponin T, NOx, ADMA, albumin, osteocalcin, cystatin C, PGLYRP1, cholesterol, HDL, LDL, triglycerides, and hemoglobin. Conclusion: A direct cause–effect association between periodontitis and CKD could not be established. However, it was possible to conclude that there was a correlating effect present, through the analyzed biomarkers. Full article

Primary malignancies of the lung, skin (melanoma), and breast have higher propensity for metastatic spread to the brain. Advances in molecular tumour profiling have aided the development of targeted therapies, stereotactic radiotherapy, and immunotherapy, which have led to some improvement in patient outcomes; however, the overall prognosis remains poor. Continued research to identify new prognostic and predictive biomarkers is necessary to further impact patient outcomes, as this will enable better risk stratification at the point of primary cancer diagnosis, earlier detection of metastatic deposits (for example, through surveillance), and more effective systemic treatments. Brain metastases exhibit considerable inter- and intratumoural heterogeneity—apart from distinct histology, treatment history and other clinical factors, the metastatic brain tumour microenvironment is incredibly variable both in terms of subclonal diversity and cellular composition. This review discusses emerging biomarkers; specifically, the biological context and potential clinical utility of tumour tissue biomarkers, circulating tumour cells, extracellular vesicles, and circulating tumour DNA. Full article

Background: Hearing impairment (HI) is a major problem in Ghana; however, the few attempts at shedding light on its causes appear to overlook the adverse effects of some medications—a gap that this study sought to fill. Aminoglycoside therapy for tuberculosis (TB) treatment is one of these medications. Aim: The aim of this study was to establish the potential of aminoglycoside as a cause of hearing impairment among patients on anti-TB treatment. Method: This was a case–control study, involving patients receiving treatment for TB with aminoglycoside at the chest clinic of the Tema General Hospital and a control group of age- and gender-matched healthy volunteers. A structured questionnaire was administered to obtain the demographic data and case history of the participants. The hearing sensitivity of the participants was assessed using conventional pure tone audiometry and transient evoked otoacoustic emission tests. Results: A hearing loss prevalence of 20% (12/60) was found among patients receiving treatment for TB, with the intensity of impairment ranging from mild to severe. Hearing thresholds of patients receiving anti-TB medications were significantly elevated (p < 0.05) in comparison to the thresholds of the control group, especially at the high frequencies. Conclusion: This study shows that aminoglycoside therapy for tuberculosis may contribute to hearing impairment among tuberculosis patients in Ghana. Audiological management of these patients should therefore be an essential part of their therapeutic treatment plan. Full article

D-amino acids may play key roles for specific physiological functions in different organs including the brain. Importantly, D-amino acids have been detected in several neurological disorders such as schizophrenia, amyotrophic lateral sclerosis, and age-related disorders, reflecting the disease conditions. Relationships between D-amino acids and neurophysiology may involve the significant contribution of D-Serine or D-Aspartate to the synaptic function, including neurotransmission and synaptic plasticity. Gut-microbiota could play important roles in the brain-function, since bacteria in the gut provide a significant contribution to the host pool of D-amino acids. In addition, the alteration of the composition of the gut microbiota might lead to schizophrenia. Furthermore, D-amino acids are known as a physiologically active substance, constituting useful biomarkers of several brain disorders including schizophrenia. In this review, we wish to provide an outline of the roles of D-amino acids in brain health and neuropsychiatric disorders with a focus on schizophrenia, which may shed light on some of the superior diagnoses and/or treatments of schizophrenia. Full article

A thyroglossal duct cyst (TGDC) is one of the most commonly encountered congenital anomalies of the neck. However, it is difficult to diagnose as differentiating it from other cysts like brachial cysts, lymphangiomas, epidermoid cysts, dermoid cysts, and hydatid cysts, is challenging. In this paper, we systematically reviewed the literature of 47 patients—25 males (53.1%) and 21 females (44.7%)—about their TGDC to assess the clinical picture, therapy, and prognosis of the disease. Most of the patients were children under the age of ten (63.8%). All patients had a history of a painless swelling in the anterior midline of the neck that moved in response to deglutition and tongue protrusion, thus interfering with their daily activity. Post-resection recurrence was unusual, with only 3 of 47 patients (6.4%) experiencing recurrence. Full article

Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] level are the most common inherited disorders of lipid metabolism. This study evaluated the impact of high Lp(a) level on accuracy Dutch Lipid Clinic Network (DLCN) criteria of heterozygous FH diagnosis. A group of 206 individuals not receiving lipid-lowering medication with low-density lipoprotein cholesterol (LDL-C) >4.9 mmol/L was chosen from the Russian FH Registry. LDL-C corrected for Lp(a)-cholesterol was calculated as LDL-C − 0.3 × Lp(a). DLCN criteria were applied before and after adjusting LDL-C concentration. Of the 206 patients with potential FH, a total of 34 subjects (17%) were reclassified to less severe FH diagnosis, 13 subjects of them (6%) were reclassified to “unlike” FH. In accordance with Receiver Operating Characteristic curve, Lp(a) level ≥40 mg/dL was associated with FH re-diagnosing with sensitivity of 63% and specificity of 78% (area under curve = 0.7, 95% CI 0.7–0.8, p < 0.001). The reclassification was mainly observed in FH patients with Lp(a) level above 40 mg/dL, i.e., 33 (51%) with reclassified DLCN criteria points and 22 (34%) with reclassified diagnosis, compared with 21 (15%) and 15 (11%), respectively, in patients with Lp(a) level less than 40 mg/dL. Thus, LDL-C corrected for Lp(a)-cholesterol should be considered in all FH patients with Lp(a) level above 40 mg/dL for recalculating points in accordance with DLCN criteria. Full article

Once patients are diagnosed with pulmonary hypertension it is important to identify the correct diagnostic group as it will have implications on the disease state management. Pulmonary hypertension is increasingly diagnosed and treated in general medical practices; however, evidence-based guidelines recommend evaluation and treatment in pulmonary hypertension centers for accurate diagnosis and appropriate treatment recommendations. We conducted a retrospective cohort study of 509 random patients 18 years and older who were evaluated in our pulmonary hypertension clinic from January 2005 to December 2018. 68.4% (n = 348) had their diagnostic group clarified or changed. Pulmonary hypertension was deemed an incorrect diagnosis in 12.4% (n = 63). A total of 114 patients (22.4%) had been initiated on pulmonary hypertension specific treatment prior to presentation. Pulmonary hypertension specific medication was stopped in 57 (50.0%) cases. The estimated monthly saving of the stopped medication based on wholesale acquisition costs was USD 396,988.05–419,641.05, a monthly saving of USD 6964.70–7362.12 per patient. Evaluation outside of a pulmonary hypertension center may lead to misdiagnosis and inappropriate or inadequate treatment. Pulmonary arterial hypertension directed therapy improves median survival, but inappropriate therapy may cause harm; therefore, patients benefit from a specialized center with multiple resources to secure an accurate diagnosis and tailored treatment for their condition. Full article

Lysine methylation is among the key posttranslational modifications to histones that contribute to epigenetic regulation. SMYD3 is a lysine methyltransferase that is essential for the proliferation of a range of tumorigenic cells. The findings that SMYD3 is significantly upregulated in most colorectal carcinomas, hepatocellular carcinomas, and breast cell carcinomas support a model in which its aberrant expression modifies established patterns of gene expression, ultimately driving unrestrained proliferation. Herein, we dissect the unique structural features of SMYD3 relative to other SET enzymes, with an emphasis on the implications for selective design of therapeutics for the clinical management of cancer. Further, we illustrate the ability of inhibitors targeting the SET domain of SMYD3 to reduce the viability of colorectal and lung carcinoma cells. Full article

Dyslipidemia is a major modifiable risk factor for ischemic stroke. Treatment with statins reduces the incidence of recurrent ischemic stroke and also reduces coronary events in patients with a history of ischemic stroke. Therefore, statins represent an important component of secondary prevention of ischemic stroke. In patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with the maximal tolerated dose of a potent statin, ezetimibe should be added to their lipid-lowering treatment and also appears to reduce the risk of cardiovascular events. Selected patients who do not achieve LDL-C targets despite statin/ezetimibe combination are candidates for receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Finally, it appears that adding icosapent ethyl might also reduce cardiovascular morbidity in patients who have achieved LDL-C targets but have persistently elevated triglyceride levels. Full article

CKDu needs to be characterized in fundamental areas to improve etiological understanding and disease management. In a cross-sectional study, blood cell profile and plasma inflammatory cytokines were followed by automated analysis and sandwich ELISA, respectively. Disease development stages and proteinuria were ascertained by eGFR and UACR. Comparison among control and stages (ANOVA/Dunnett’s MRT) revealed time-specific changes (p < 0.05), including decreased erythrocytes (G5) and hematocrit (G5), and increased MCHC (G3b, G4), MCV (G5), and MCH (G5). CKDu decreased (p < 0.05) lymphocytes (G3b, G4, G5), monocytes (G3b), MPV (G3b, G4, G5), and plateletcrit (G3b, G4), and increased basophils (G3a, G3b, G4), N/L (G4) and PLR (G4–G5). MCHC and aforesaid leukocyte variables were in correlation (rho > ±0.03, p < 0.05, Pearson’s test) with disease development. MCP-1 and IL-6 spiked (p > 0.05) at G3b. Multivariate analyses confirmed that MCP-1, lymphocytes, and BMI were related to renal dysfunction, pointing to inflammation, compromised immunity, and muscle wasting as CKDu effects. Nonproteinuric CKDu was prevalent (23.2–35.6% of total CKDu) with (p < 0.05) elevated basophils (G3a), N/L (G4), and depleted lymphocytes (G4). In both forms, G1–G2 were unaffected, and the earliest change was G3a basophils. Results suggest that MCP-1, lymphocyte count, N/L, and PLR may verify the stage and predict impending ESRD in advance proteinuric CKDu. Full article

COVID-19 has a devastating impact worldwide. Recognizing factors that cause its progression is important for the utilization of appropriate resources and improving clinical outcomes. In this study, we aimed to identify the epidemiological and clinical characteristics of patients who were hospitalized with moderate versus severe COVID-19 illness. A single-center, retrospective cohort study was conducted between 3 March and 9 September 2020. Following the CDC guidelines, a two-category variable for COVID-19 severity (moderate versus severe) based on length of stay, need for intensive care or mechanical ventilation and mortality was developed. Data including demographic, clinical characteristics, laboratory parameters, therapeutic interventions and clinical outcomes were assessed using descriptive and inferential analysis. A total of 1002 patients were included, the majority were male (n = 646, 64.5%), Omani citizen (n = 770, 76.8%) and with an average age of 54.2 years. At the bivariate level, patients classified as severe were older (Mean = 55.2, SD = 16) than the moderate patients (Mean = 51.5, SD = 15.8). Diabetes mellitus was the only significant comorbidity potential factor that was more prevalent in severe patients than moderate (n = 321, 46.6%; versus n = 178, 42.4%; p < 0.001). Under the laboratory factors; total white cell count (WBC), C-reactive protein (CRP), Lactate dehydrogenase (LDH), D-dimer and corrected calcium were significant. All selected clinical characteristics and therapeutics were significant. At the multivariate level, under demographic factors, only nationality was significant and no significant comorbidity was identified. Three clinical factors were identified, including; sepsis, Acute respiratory disease syndrome (ARDS) and requirement of non-invasive ventilation (NIV). CRP and steroids were also identified under laboratory and therapeutic factors, respectively. Overall, our study identified only five factors from a total of eighteen proposed due to their significant values (p < 0.05) from the bivariate analysis. There are noticeable differences in levels of COVID-19 severity among nationalities. All the selected clinical and therapeutic factors were significant, implying that they should be a key priority when assessing severity in hospitalized COVID-19 patients. An elevated level of CRP may be a valuable early marker in predicting the progression in non-severe patients with COVID-19. Early recognition and intervention of these factors could ease the management of hospitalized COVID-19 patients and reduce case fatalities as well medical expenditure. Full article