Asymptomatic Period Research Articles

Clinical and genetic profile of Chinese children with Danon disease: A single-center retrospective cohort study

BackgroundDanon disease (DD) is a rare X-linked dominant lysosomal storage disorder. Studies on DD pediatric patients are limited due to the small number of cases and challenges in early detection. MethodsWe retrospectively analyzed clinical and genetic data of 29 pediatric patients who visited our hospital for treatment or genetic counseling of DD from July 2014 to December 2023. ResultsThe mean age at diagnosis was 7.2±5.9 years for males (n=21) and 9.4±5.0 years for females (n=8). Asymptomatic elevated liver aminotransferase and/or creatine kinase (CK) levels were initial manifestations detected in 10 (48%) male patients and absent in female patients. Hypertrophic cardiomyopathy (HCM) was observed in 20 (95%) male and 7 (88%) female patients, while dilated cardiomyopathy (DCM) was not detected. Ventricular preexcitation (VP) was observed initially in 10 (36%) patients and in 15 (54%) at latest evaluation. Patients with VP had higher left ventricular posterior wall thickness in diastole z-scores than those without VP (5.6±2.2 vs. 3.5±2.1, p=0.029). During a median 2.7-years follow-up, two males received heart transplants. One boy and one girl died of heart failure and sudden cardiac arrest, respectively. Twenty-three pathogenic LAMP2 variants were identified, including seven novel variants. ConclusionsA retrospective review of 29 DD cases suggests an underrecognized asymptomatic period in male DD patients, characterized by elevations in serum CK and transaminases. HCM appears to be the only cardiac manifestation in pediatric female patients, unlike a high incidence of DCM in adult female patients. The incidence of VP may increase with disease progression.

Clinical and Radiological Profile of Nine Patients with Metachromatic Leukodystrophy

Introduction: Metachromatic leukodystrophy (MLD) is a rare, demyelinating, autosomal recessive lysosomal storage disease caused by a deficiency in the arylsulfatase A enzyme (ASA), which is encoded by ARSA gene. A lack of ASA activity results in an accumulation of sulfatides in the myelin sheaths of both the central and peripheral nervous systems, leading to developmental and neurocognitive progressive deterioration that can be observed in all age groups. Methods: We present a total of 9 patients with MLD with an average age of 61 months, whose clinical, laboratory and cranial magnetic resonance imaging findings were evaluated, and who underwent an ARSA gene molecular analysis. Results: Of the 9 patients, 7 had the late infantile form of the condition, 2 had the juvenile form, and 3 were identified through family screening. The median age at diagnosis was 30 months (min 3–max 73 months), the mean ASA activity value was 2 nmol/h/mgprt and the median cranial MR imaging severity score was 10 (min 5–max 18). The grey and white matter volumes of all patients, evaluated using volBrain software, were within the normal range. At an average age of 48 months, the late-infantile MLD patients were unable to control any body part. Conclusions: Hematopoietic stem cell transplantation (HSCT), a treatment option for both the juvenile and adult forms of MLD in asymptomatic or early symptomatic patients, was performed on two of the asymptomatic and early symptomatic patients, and post-HSCT ASA activity settled within the normal range and their developmental milestones stabilized. It is important to diagnose MLD in the asymptomatic period and newborn screening can support early diagnosis.

Recurrent GBS in Children: A Case Report

Background: Guillain-Barré Syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy characterized by rapidly progressing muscle weakness. GBS usually follows a monophasic course, but rarely it can recur after an asymptomatic period of several months to years. Limited cases of recurrent GBS have been reported in the literature. We present two cases of recurrent GBS encountered in a tertiary care hospital. This case report describes the clinical presentation, diagnostic workup, management, and outcomes of two children of GBS who experienced recurrence. By presenting the cases, we aim to increase awareness of this rare presentation of GBS among healthcare professionals and enabletimely recognition and better outcomes for children with recurrent GBS. J Com Med Col Teachers Asso Jan 2024; 28(1): 37-40

Case Report: Gallstone ileus management - Case report and review of the literature

Gallstone ileus, a rare complication of cholelithiasis, presents significant morbidity and mortality challenges, with no established consensus on optimal management. This study aimed to highlight the complexities surrounding its occurrence and emphasize the need for tailored therapeutic strategies. An 88-year-old female, with a history of type 2 diabetes mellitus presented with diffuse abdominal pain and vomiting. Clinical evaluation revealed signs of small-bowel obstruction. Radiological assessments, including Computed Tomography CT) scans, confirmed biliary ileus, showcasing a sizable gallstone causing subacute obstruction. Emergency surgery involving enterolithotomy was performed, successfully addressing the immediate concerns. Postoperative follow-up demonstrated a one-year asymptomatic period, emphasizing the effectiveness of the chosen intervention. Gallstone ileus typically follows acute cholecystitis, leading to gallstone erosion and fistula formation commonly in the duodenum. Diagnosis is challenging because of nonspecific symptoms, necessitating a high index of suspicion. Computed tomography (CT) plays a pivotal role in accurate and rapid diagnoses. This study delves into the intricate details of gallstone ileus presentation, complications, and the debate surrounding optimal surgical management, acknowledging the effectiveness of the two-stage procedure and emerging laparoscopic approaches. This case provides valuable insights into the intricate facets of gallstone ileus and emphasizes the need for individualized treatment strategies. Successful management, as demonstrated in our case, underscores the importance of considering patient-specific factors when choosing between the surgical approaches. This study supports recent reports advocating for laparoscopic interventions, encouraging further exploration of evolving therapeutic modalities for gallstone ileus.

The Significance of Off-Season Tailor-Made Baseline Measurements in the Assessment of Post-Concussion in University Athletes.

This study aimed to investigate the significance of baseline measurements for amateur team athletes playing contact and collision team sports with a specific focus on the Sports Concussion Assessment Tool (SCAT) to improve concussion management. Symptoms of sports-related concussions (SRCs) can be diverse and long-lasting and include cognitive impairment, sleep disturbances, and vestibular dysfunction. Therefore, comprehensive baseline data are essential to preventing recurrent concussions and secondary injuries. This study was conducted during the 2023 off-season and evaluated the baseline condition of 65 male university rugby players using the SCAT5, which includes self-reported symptoms, and the modified Balance Error Scoring System (mBESS). The athletes were assessed for the presence or absence of SRC, and the mean values were compared using the Mann-Whitney U test. Among the participants, 35.38% (23/65) reported symptoms, with an average of 1.5 ± 2.8 symptoms per player and an average symptom score of 2.66 ± 5.93. In the mBESS, no errors were observed in the tandem stance test; however, 72.31% (47/65) made errors in the single-leg stance test on the non-dominant foot, with an average of 1.7 ± 1.5 errors. Many athletes self-reported symptoms and balance errors, even during asymptomatic periods before experiencing concussion, indicating unresolved issues. In the injury history survey, the baseline evaluations and injury histories of the participants classified into the SRC and non-SRC groups were compared. In the mBESS single-leg stance test (non-dominant foot), 84.21% (32/38) of the SRC group participants made errors, with an average score of 2.13 ± 1.52, whereas 55.55% (15/27) of the non-SRC group participants made errors, with an average score of 1.15 ± 1.35, showing a significant difference (p = 0.007). Additionally, significant differences were observed in the average number of ankle sprains (p = 0.027) and fractures (p = 0.048) between patients with and without a history of SRC. These findings indicate that athletes may have underlying issues even during normal periods before concussion. Moreover, the results highlighted the impact of previous concussions on motor control and injury risk. This underscores the importance of preseason baseline measurements using the SCAT to identify at-risk athletes and implement preventive measures. These findings align with the recommendations of the 6th International Conference on Concussion in Sport and suggest further refinement of concussion assessment tools.

Metal hypersensitivity in trapeziometacarpal arthroplasty: A systematic pattern of progression

Metal hypersensitivity is a rare and often underestimated complication, as shown by the small number of published studies, particularly concerning the upper limbs and the hand. However, the increase in the annual number of trapeziometacarpal arthroplasties underlines the importance of better understanding of this problem.We performed a study based on data from the revision of trapeziometacarpal prostheses to assess the incidence of this complication and to define a sequence of radiological changes to detect metal hypersensitivity.This single-center retrospective study included 37 patients operated on between January 2014 and November 2023 for revision of trapeziometacarpal prosthesis. Ten (27%) had no clearly identified cause of failure.For these 10 patients, we analyzed clinical data and postoperative X-rays. In the 11 revision arthroplasties, 2 patients had no symptoms or radiographic signs suggestive of allergy. Six patients had a-posteriori diagnosis established by allergy testing, which also identified 2 additional patients, for a total of 8 patients (21% of the initial cohort). In these cases, there was systematic metaphyseal osteolysis of the first metacarpal between 15 days and 1 month after implantation. Clinically, most patients had an asymptomatic period of 2 weeks to 1 month before onset of symptoms and osteolysis, often accompanied by local inflammation.This study found a reproducible pattern of progression, characterized by the appearance of radiographic signs of osteolysis in the first month, followed by clinical deterioration. Although this course is strongly suggestive of a metal hypersensitivity, it is crucial not to exclude the possibility of an infectious cause, which should always be considered.

Multimodal Machine Learning-Based Marker Enables Early Detection and Prognosis Prediction for Hyperuricemia.

Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.

PET Study of Microglial Activation in Kleine-Levin Syndrome.

Kleine-Levin syndrome (KLS) is a rare recurrent hypersomnolence disorder associated with cognitive and behavioral disturbances, of unknown origin, but inflammatory mechanisms could be involved. We aimed to explore in vivo microglia activation using [18F]DPA-714 PET imaging in patients with KLS compared with controls, and during symptomatic vs asymptomatic periods. Patients with KLS and controls underwent a standardized clinical evaluation and PET imaging, using a radiolabeled ligand specific to the 18 kDa translocator protein. Images were processed on the PMOD (peripheral module) interface using a standard uptake value (SUV). Five regions of interest (ROIs) were analyzed: hypothalamus, thalamus, frontal area, cerebellum, and whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake. Images of 17 consecutive patients with KLS (7 during episodes, 10 out of episodes) and 14 controls were analyzed. We found no SUV/SUVr difference between KLS and controls, between patients in and out episodes in all ROIs, and no correlation between SUVr and episode duration at the time of PET scan. No association was found between SUVr and sex, disease duration, or orexin levels. Our findings do not support the presence of neuroinflammation in KLS. Further research is needed to identify relevant biomarkers in KLS.

PATHOPHYSIOLOGICAL, NEUROCHEMICAL AND BRAIN IMAGING ANALYSIS AS PARAMETERS FOR THE EARLY DIAGNOSIS OF BIPOLAR DISORDER

Introduction: Bipolar affective disorder is a complex psychiatric disorder. Its most striking feature is the alternation, sometimes sudden, of episodes of depression with those of euphoria (mania and hypomania) and asymptomatic periods in between. The crises can vary in intensity (mild, moderate and severe), frequency and duration. Objectives: The aim of this study was to identify the pathophysiology and neurochemistry of bipolar disorder, from diagnosis to treatment. Material and Methods: The methodology used was a literature review. The research was carried out through an electronic search for scientific articles published on the Scielo (Scientific Electronic Library Online) and Lilacs (Latin American Health Sciences Literature) and Pubmed websites. The health terminologies consulted in the Health Sciences descriptors (DeCS/BIREME) were used; the pathophysiology and neurochemistry of bipolar disorder, from diagnosis to treatment. Results: Structural neuroimaging studies have shown significant changes in brain volume, suggesting atrophy and/or neuronal loss, at least in a proportion of individuals with BD. Several studies have reported a significant decrease in gray matter in the prefrontal and temporal cortex, as well as an increase in the lateral ventricles. Bipolar patients tend to show reductions in gray matter in the frontal regions of the brain involved in self-control, while sensory and visual regions are normal. Conclusion: When struggling with a mental health disorder, the road to improvement usually begins with the long process of trying various treatments and approaches to find the one that best suits the patient.

Healthcare Provider-Related Factors in the Diagnostic Delay of Cervical Cancer: A Cross-Sectional Study.

Background and objective Cervical cancer is the second most common malignancy among Indian women. In 2018, the World Health Organization (WHO) called for global action toward the elimination of cervical cancer through the triple-intervention strategy. One of its pillars is ensuring 70% screening coverage of eligible women with a high-performance test at least twice in their lifetime. Various factors contribute to the delayed diagnosis of cervical cancer, increasing the burden of the disease. In this study, we aimed to determine the healthcare provider (HCP)-related factors in the diagnostic delay of advanced cervical cancer. Methods This prospective cross-sectional study was conducted over two months in the cancer clinic of the Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. We interviewed 384 women diagnosed with advanced cervical cancer [the International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IVB] by using a questionnaire to capture data inputs regarding the various healthcare services they had received in the past 10 years along with details of HCPs. The collected data were analyzed using the software STATA version 17.0. Results Among 384 participants, 185 (48.1%) had interacted with an HCP in the past 10 years; 157 (40.8%) of them had visited a healthcare facility.Among these 185 women, only 22.16% had been advised to undergo screening, and only 15.18% had been tested despite several having access to primary health centers within 10 km of their residence. The lack of screening guidance by HCPs accounted for 78% of delayed diagnoses of cervical cancer. Conclusions Based on our findings, a deficiency in screening guidance in the asymptomatic period by healthcare providers across various levels of our healthcare system contributed significantly to the delayed diagnosis of cervical cancer.

WELLENS SYNDROME: TIMELY RECOGNITION AND SUCCESSFUL REVASCULARIZATION

Abstract Wellens syndrome is a condition characterized by clinical and instrumental signs suggestive of a critical proximal left anterior descending (LAD) coronary artery stenosis and requires early revascularization. Diagnostic criteria include T–wave changes in ECG during asymptomatic periods in patients with a history of chest pain, absence of significant cardiac enzyme movement, no ST–segment elevation, preserved R–wave, and no pathological Q waves. Early recognition of this syndrome is crucial, due to its 10–15% prevalence, allowing proper management and myocardial function recovery, avoiding potentially catastrophic outcomes. A 64–year–old male, with hypertension, undiagnosed diabetes, and family history of CAD, presented to our ER with sudden, brief chest pain radiating to the left upper limb. Similar episodes had occurred in the past week. The patient denied previous cardiovascular events and home therapy. ECG conducted by the attending cardiologist, during free chest pain period, showed biphasic T–wave in V1–V3 (a). Admission ECG resembled the ambulatory one. Lab results: Hb 14.7 g/dl, Troponin I 0.059 ng/ml (cut–off 0.034). Echocardiogram indicated distal septum akinesia. Urgent coronary angiography was performed, detecting subocclusive stenosis in the proximal–mid LAD. Successful revascularization was achieved by PTCA and implantation of 1 DES. (b) Subsequently, the patient was admitted to the Cardiac Intensive Care Unit for multiparametric monitoring. The ECG showed deeply negative T waves from V1 to V6. (c) No complications during hospitalization. Discharge ECG showed repolarization anomalies improvement. Echocardiography revealed preserved systolic function, without global or segmental anomalies in wall motion. Wellens syndrome is a manifestation of acute coronary syndrome that precedes an anterior wall MI. This condition can be identified by its characteristic T–wave patterns on ECG. Patients with this syndrome have severe LAD occlusion and require early coronary intervention. In chest pain episodes, the ECG appears normal, and troponin levels often remain within the normal range, which can potentially provide false reassurance. Wellens syndrome is a cardiac emergency requiring immediate attention; it is crucial for the physician to promptly identify the typical ECG signs of Wellens Syndrome, facilitating early coronary revascularization to prevent adverse patient outcomes.

Mesenteric Ischemia after Cardiac Surgery.

Mesenteric ischemia (Me-Is) after cardiac surgery is underreported in present literature but has still earned the bad reputation of a dismal prognosis. This study adds clinical outcomes in a large patient cohort. Between 2009 and 2019 of the 22,590 patients undergoing cardiac surgery at our facility 106 (0.47%) developed Me-Is postoperatively. Retrospective patient data was analyzed. Additionally, patients were stratified by outcome-survivors and nonsurvivors. Patients were predominantly male (n = 68, 64.2%), mean age was 71.2 ± 9.3 years. Most procedures were elective (n = 85, 80.2%) and comprised of more complex combined procedures (50.9%) and redos (17.9%). Mean EuroSCORE II averaged 10.9 ± 12.2%. Survival at 30 days was 49.1% (n = 52). Clinical baseline and procedural characteristics did not differ significantly between survivors and nonsurvivors. The median postoperative interval until symptom onset was 5 days in both groups. Survivors were more frequently diagnosed by computed tomography and nonsurvivors based on clinical symptoms. Me-Is was predominantly nonocclusive (n = 84, 79.2%). Laparotomy was the main treatment in both groups (n = 45, 78.8% vs. n = 48, 88.9%, p = 0.94). Predictors of mortality were maximum norepinephrine doses (hazard ratio [HR] 8.29, confidence interval [CI] 3.39-20.26, p < 0.0001), lactate levels (HR 1.06, CI 1.03-1.09), and usage of inotropes (HR 2.46, CI 1.41-4.30). The prognosis of Me-Is following cardiac surgery is poor-independently from diagnostic or treatment patterns. There exists a significant asymptomatic time period postoperatively, in which pathophysiologic processes seem to cross the Rubicon. After clinical demarcation, the further course can almost no longer be influenced.

Toward Telemonitoring in Immune-Mediated Inflammatory Diseases: Protocol for a Mixed Attention Model Study.

Rheumatic and musculoskeletal diseases (RMDs) are chronic diseases that may alternate between asymptomatic periods and flares. These conditions require complex treatments and close monitoring by rheumatologists to mitigate their effects and improve the patient's quality of life. Often, delays in outpatient consultations or the patient's difficulties in keeping appointments make such close follow-up challenging. For this reason, it is very important to have open communication between patients and health professionals. In this context, implementing telemonitoring in the field of rheumatology has great potential, as it can facilitate the close monitoring of patients with RMDs. The use of these tools helps patients self-manage certain aspects of their disease. This could result in fewer visits to emergency departments and consultations, as well as enable better therapeutic compliance and identification of issues that would otherwise go unnoticed. The main objective of this study is to evaluate the implementation of a hybrid care model called the mixed attention model (MAM) in clinical practice and determine whether its implementation improves clinical outcomes compared to conventional follow-up. This is a multicenter prospective observational study involving 360 patients with rheumatoid arthritis (RA) and spondylarthritis (SpA) from 5 Spanish hospitals. The patients will be followed up by the MAM protocol, which is a care model that incorporates a digital tool consisting of a mobile app that patients can use at home and professionals can review asynchronously to detect incidents and follow patients' clinical evolution between face-to-face visits. Another group of patients, whose follow-up will be conducted in accordance with a traditional face-to-face care model, will be assessed as the control group. Sociodemographic characteristics, treatments, laboratory parameters, assessment of tender and swollen joints, visual analog scale for pain, and electronic patient-reported outcome (ePRO) reports will be collected for all participants. In the MAM group, these items will be self-assessed via both the mobile app and during face-to-face visits with the rheumatologist, who will do the same for patients included in the traditional care model. The patients will be able to report any incidence related to their disease or treatment through the mobile app. Participant recruitment began in March 2024 and will continue until December 2024. The follow-up period will be extended by 12 months for all patients. Data collection and analysis are scheduled for completion in December 2025. This paper aims to provide a detailed description of the development and implementation of a digital solution, specifically an MAM. The goal is to achieve significant economic and psychosocial impact within our health care system by enhancing control over RMDs. ClinicalTrials.gov NCT06273306; https://clinicaltrials.gov/ct2/show/NCT06273306. PRR1-10.2196/55829.

Biofilm in Cochlear Implant: A Surgeon’s Diagnosis

Biofilms in a cochlear implant can lead to severe intracranial complications like meningitis, and it can cause implant failure, thus requiring an explant, leading to financial and social loss. Meticulous sterility in the intraoperative period and proper hygiene in the postoperative period need to be emphasized in a cochlear implant Patient. We report a case of a 4-year-old girl child who presented with recurrent episodes of wound dehiscence through the cochlear implant site following the asymptomatic period after a course of antibiotics, and finally treated with debridement and flap reconstruction under general anaesthesia. We sought to use novel agents with antimicrobial activity in addition to debridement, vascularized soft tissue cover, and oral rifampicin after surgery. The child underwent serial surgeries, and finally, the use of medical grade Manuka honey and rifampicin demonstrated a successful response to biofilm up to a two-month follow-up period. This case revealed that biofilm is primarily a surgeon’s diagnosis.

Low TGF-β1 plasma levels are associated with cognitive decline in Down syndrome.

Almost all individuals with Down's syndrome (DS) show the characteristic neuropathological features of Alzheimer's disease (AD) by the age of 40, yet not every individual with DS experiences symptoms of AD later in life. Similar to neurotypical developing subjects, AD in people with DS lasts for a long preclinical phase in which biomarkers follow a predictable order of changes. Hence, a prolonged asymptomatic period precedes the onset of dementia, underscoring the importance of identifying new biomarkers for the early detection and monitoring of cognitive decline in individuals with DS. Blood-based biomarkers may offer an alternative non-invasive strategy for the detection of peripheral biological alterations paralleling nervous system pathology in an early phase of the AD continuum. In the last few years, a strong neurobiological link has been demonstrated between the deficit of transforming growth factor-β1 (TGF-β1) levels, an anti-inflammatory cytokine endowed with neuroprotective activity, and early pro-inflammatory processes in the AD brain. In this clinical prospective observational study, we found significant lower plasma TGF-β1 concentrations at the first neuropsychological evaluation (baseline = T0) both in young adult DS individuals (19-35years) and older DS subjects without AD (35-60years) compared to age- and sex-matched healthy controls. Interestingly, we found that the lower TGF-β1 plasma concentrations at T0 were strongly correlated with the following cognitive decline at 12 months. In addition, in young individuals with DS, we found, for the first time, a negative correlation between low TGF-β1 concentrations and high TNF-α plasma concentrations, a pro-inflammatory cytokine that is known to be associated with cognitive impairment in DS individuals with AD. Finally, adopting an ex vivo approach, we found that TGF-β1 concentrations were reduced in parallel both in the plasma and in the peripheral blood mononuclear cells (PBMCs) of DS subjects, and interestingly, therapeutic concentrations of fluoxetine (FLX) applied to cultured PBMCs (1µM for 24h) were able to rescue TGF-β1 concentrations in the culture media from DS PBMCs, suggesting that FLX, a selective serotonin reuptake inhibitor (SSRI) endowed with neuroprotective activity, might rescue TGF-β1 concentrations in DS subjects at higher risk to develop cognitive decline.

Natural history of asymptomatic gallbladder stones in clinic without beds: A long-term prognosis over 10 years.

Several studies have explored the long-term prognosis of patients with asymptomatic gallbladder stones. These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases. To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities. We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022. When symptoms developed, patients were transferred to hospitals where appropriate treatment was possible. We investigated the asymptomatic and survival periods during the follow-up. Among the 237 patients, 214 (90.3%) remained asymptomatic, with a mean asymptomatic period of 3898.9279 ± 46.871 d (50-4111 d, 10.7 years on average). Biliary complications developed in 23 patients (9.7%), with a mean survival period of 4010.0285 ± 31.2788 d (53-4112 d, 10.9 years on average). No patient died of biliary complications. The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable. When the condition became symptomatic, the patients were transferred to hospitals with beds that could address it; thus, no deaths related to biliary complications were reported. This finding suggests that follow-up care in clinics without beds is possible.

Cell and animal models of age‐related macular degeneration: Focus on oxidative stress and protein aggregation

Age‐related macular degeneration (AMD) is a multifactorial disease with a long asymptomatic development period. Due to its multifactorial feature and slow development, disease modelling capturing all the elements becomes difficult if not impossible. The disease has a strong genetic background in form of certain polymorphisms in the complement system and ARMS2/HTRA1 genes providing tools for studies regarding genetics. However, AMD is much more than genetics. At least prolonged oxidative stress and subsequent protein accumulation and aggregation together with local inflammation developing to chronic in retinal pigment epithelial (RPE) cells are the key elements of the cellular pathogenesis of AMD. The RPE cells are quiescent and responsible for the wellbeing of the entire retina functioning as the link between choroidal vasculature and other layers of the retina providing necessary support for normal retinal functions. Therefore, disturbance on the cellular homeostasis of the RPE compromise the function of the entire retina. Despite being such an integral part of the retina responsible for the vision, the RPE cells withstand one the highest levels of oxidative stress throughout a lifetime of an individual. This sets certain demands for the antioxidant system's capacity to eliminate harmful oxidant molecules and prevent the spread of oxidative injury inside the cell leading to oxidative stress. However, constant oxidative challenge leads to damages on the protective system and becomes more deleterious over time. Proteins are especially prone to oxidative damage resulting increased levels of dysfunctional or aggregating proteins challenging the repair/degradative systems of the cell. Modification of oxidative status or protein degradation systems have been shown to simulate the disease state in the RPE cells and leading to a disease resembling phenotype. In vitro models are efficient tools studying certain cell specific molecular pathways such as oxidative stress, function of antioxidant defence system, and repair/degradative pathways and discovering potential druggable targets. In vivo animal models offer information how these pathways function in a native environment and how the in vitro results are translated to a functional living organism. Also, animal models offer information about the potential administration routes as well as important pharmacological data, for example. The use of most common animals in research, rodents, needs genetic engineering, for example, to achieve desired disease modelling phenotype often lacking some critical features of the disease. However, the use of these models has greatly increased the understanding of AMD pathogenesis, lead to new discoveries on disease development later confirmed in patient population, and offered new treatment strategies.

Global Stability Indices of the Transmission and Bilinear Control Functions for Tobacco Smoking Epidemic

Background: The seeming insurmountable effect of tobacco-smoking, coupled with intense laxity by society towards the avalanche consequential effects of tobacco-smoking consumption and the yet-to-be-available mathematical model for comprehensive treatment of multiple effects of tobacco-smoking, necessitated this present investigation. The present research arguably presented an insight into the global stability indices of not just the impact of smoking transmission but explicitly demonstrated the methodological application of designated bilinear control functions in the presence of screening techniques for the eradication of consequential effects of smoking and tobacco consumption. Methods: The model explored deterministic 6-subpopulations, formulated using first-order differential equations. System interactions was investigated using bilinear control functions with system well-posedness established. Furthermore, system smoking generation number for both off- and onsettreatment scenarios was determined. Analytic predictions for both local and global indices explored second additive compound matrix in conjunction with Lozinski measure . Numerical simulations evolved Runge-Kutta of order of precision 4 in a Mathcad surface. Results: Accompanying simulations indicated protracted initial asymptomatic saddle period of smoking infection for t f &lt; 140 days under the off-treatment scenario. Inducement of bilinear control functions under screening method yielded drastic reduction to near zero within the first t f &lt; 80 days as vindicated by the exponential rejuvenation of potential smokers. Conclusion: Investigation concludes that eradication of consequential effects of tobacco-smoking is achievable provided both smokers, tobacco companies and the governments implement concurrently, the application of designated bilinear control functions the world over. Immensely, the study exhibits mutual benefits to the society and scientists in the field of Bio-mathematics and epidemiologists.

Impact of Early Diagnostic and Therapeutic Interventions and Clinical Course in Children and Adolescents with Multiple Endocrine Neoplasia Types 1 and 2.

Multiple endocrine neoplasia types 1 (MEN1) and 2 (MEN2) are inherited endocrine tumor syndromes caused by mutations in the MEN1 or RET genes. This study aimed to investigate clinical outcomes and molecular characteristics among children with MEN. This study included eight patients from seven unrelated families. Data on clinical course, biochemical findings, and radiologic studies were collected by retrospective chart review. All diagnoses were genetically confirmed by Sanger sequencing of MEN1 in three MEN1 patients and RET in four patients with MEN2A and one patient with MEN2B. Three patients with MEN1 from two families presented with hypoglycemia at a mean age of 11±2.6 years. Four patients with MEN2A were genetically diagnosed at a mean of 3.0±2.2 years of age by family screening; one of them was prenatally diagnosed by chorionic villus sampling. Three patients with MEN2A underwent prophylactic thyroidectomy from 5 to 6 years of age, whereas one patient refused surgery. The patient with MEN2B presented with a tongue neuroma and medullary thyroid carcinoma at 6 years of age. Subsequently, he underwent a subtotal colectomy because of bowel perforation and submucosal ganglioneuromatosis at 18 years of age. This study described the relatively long clinical course of pediatric MEN with a mean follow-up duration of 7.5±3.8 years. Insulinoma was the first manifestation in children with MEN1. Early diagnosis by family screening during the asymptomatic period enabled early intervention. The patient with MEN2B exhibited the most aggressive clinical course.

Diagnosis, combined treatment, and long-term follow-up of a thymoma patient

Thymic neoplasms account for 20 – 25% of primary mediastinal tumors. Nonspecific clinical symptoms are often associated with delayed diagnosis of thymoma, leading to a distinctive problem of late diagnosis. Nowadays, surgical removal of the tumor is the method of choice for thymoma treatment. Combination treatment is indicated in the case of an unresectable tumor. Modern therapy (various combinations of anticancer drugs) helps reduce neoplasm size, stop metastasis, and maintain good quality of life in patients with thymoma.Aim. The presented clinical case of type B3 thymoma (with invasion into surrounding organs and metastatic pleura) is characterized by a long asymptomatic period of the disease, the onset of symptoms after suffering COVID-19 (COronaVIrus Disease 2019) and successful long-term polychemotherapy. The causes of late diagnosis, as well as insufficient oncologic vigilance in evaluating the results of laboratory and instrumental tests, are discussed based on this clinical case.Conclusion. A correct diagnosis, as well as successful treatment, requires a multidisciplinary approach involving physicians from different specialties – general practitioners, oncologists, surgeons, radiologists, and morphologists.