Modern Medical Era Research Articles

Osteoporosis and Normocalcemic Primary Hyperparathyroidism (Conservatively or Surgically Managed).

Asymptomatic primary hyperparathyroidism (PHPT) involves 80-90% of the parathyroid tumor-associated cases of PHPT in the modern medical era, while normocalcemic PHPT (NPHPT) has a prevalence of 0.1-11%. We aimed to analyze the bone status and mineral metabolism in NPHPT amid conservative or surgical management. In this narrative review, we searched PubMed (between January 2020 and July 2024) via different keywords. Fourteen studies from the final analysis (388 patients with NPHPT; 1188 with PHPT; and 803 controls) showed that mean serum calcium levels varied between 2.57 and 2.26 mmol/L in NPHPT. Ten studies identified a similar 24 h urinary calcium in NPHPT versus hypercalcemic PHPT (HPHPT). Except for one study, a mandatory vitamin D analysis was performed, but the 25-hydroxyvitamin D cut-offs varied. Osteoporosis (n = 6 studies; N = 172 with NPHPT) was confirmed in 41.7-100% of NPHPT subjects. In surgery candidates, this rate might be overestimated. A DXA analysis was performed in eight studies (235 subjects with NPHPT, and 455 patients with HPHPT); two studies identified a lower BMD in HPHPT < NPHPT, but the results were not homogenous. A single study analyzed the TBS and found similar results in NPHPT. The prevalence of fractures (n = 9) varied between 7.4% and 42.8% in NPHPT. Bone turnover markers (N = 262 patients, n = 8 studies) showed lower bone formation markers in NPHPT versus PHPT (n = 3). Two studies analyzed the BMD and bone turnover markers following parathyroidectomy (161 patients, including 30 patients with NPHPT; mean ages over 60 years). To conclude, given the wide spectrum of complications associated with PHPT, an early diagnosis and proper management is essential. A more extensive screening in patients with osteoporosis and kidney stones might lead to the discovery of NPHPT, a more recently described form of PHPT. While it is still unclear whether NPHPT is an early stage of HPHPT or a separate entity, recent findings show similar osteoporosis and fracture occurrence, and an improvement in bone metabolism, following parathyroidectomy. More extensive prospective studies are crucial to understand the natural course of the disease, to reach a consensus regarding parathyroidectomy indications and surgery candidates' selection, and to ensure proper personalized management for these patients. With the evolving diagnosis methods, PHPT has become a condition with a changing clinical presentation, which now requires modern evaluation and treatment approaches.

Role of epinephrine in attenuating cytokine storm, decreasing ferritin, and inhibiting ferroptosis in SARS-CoV-2

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019. It presents one of the most threatening pandemics in the history of humanity. The mortality and morbidity represent an unprecedented challenge to the modern medical era. SARS-CoV-2 results in acute respiratory distress syndrome, high concentrations of proinflammatory mediators, cytokine storm (CS) due to massive release of cytokines, hypercoagulation, and hemoglobin disintegration. Dysregulation of iron homeostasis, iron overload as indicated by high ferritin level, and ferroptosis are major factors in the pathogenesis of the disease. We report a case of SARS-CoV-2 in which the use of epinephrine (Epi) resulted in an unexpected attenuation of CS, decreasing ferritin level and inhibiting ferroptosis.Case presentationA 64-year-old male patient with a history of multiple medical comorbidities had been diagnosed with SARS-CoV-2. Further evaluation showed marked increase in inflammatory markers, severe hyperferritinemia, and lymphopenia in laboratory blood tests. The characteristic score of CS was strongly positive, and in addition to regular treatment, the patient received Epi due to development of acute generalized skin rash, severe itching, and edema of lips and tongue. Epi may have successfully terminated not only the acute cutaneous condition, but also have attenuated CS, decreased ferritin level, and other inflammatory markers in addition to complete patient’s recovery.ConclusionEpinephrine may attenuate CS and inhibit ferroptosis which is an iron-dependent, non-apoptotic mode of cell death. Epi interacts with ferric and/or ferrous iron and built a stable complex that impedes activation of beta-adrenergic receptors. Epi may cause marked decrease of ferritin and other inflammatory markers. Epi may be used to decrease iron overload which is associated with many medical diseases like type 2 diabetes mellitus and cardiometabolic diseases such as coronary heart disease and cerebrovascular disease. As a new clinical indication extensive studies are required for further assessment and possible therapeutic uses.

Combating antimicrobial resistance: the silent war.

Once hailed as miraculous solutions, antibiotics no longer hold that status. The excessive use of antibiotics across human healthcare, agriculture, and animal husbandry has given rise to a broad array of multidrug-resistant (MDR) pathogens, posing formidable treatment challenges. Antimicrobial resistance (AMR) has evolved into a pressing global health crisis, linked to elevated mortality rates in the modern medical era. Additionally, the absence of effective antibiotics introduces substantial risks to medical and surgical procedures. The dwindling interest of pharmaceutical industries in developing new antibiotics against MDR pathogens has aggravated the scarcity issue, resulting in an exceedingly limited pipeline of new antibiotics. Given these circumstances, the imperative to devise novel strategies to combat perilous MDR pathogens has become paramount. Contemporary research has unveiled several promising avenues for addressing this challenge. The article provides a comprehensive overview of these innovative therapeutic approaches, highlighting their mechanisms of action, benefits, and drawbacks.

1-Benzyl-5-bromo-3-hydrazonoindolin-2-ones as Novel Anticancer Agents: Synthesis, Biological Evaluation and Molecular Modeling Insights

Human health is experiencing several obstacles in the modern medical era, particularly cancer. As a result, the cancer therapeutic arsenal should be continually expanded with innovative small molecules that preferentially target tumour cells. In this study, we describe the development of two small molecule series (7a-d and 12a-e) based on the 1-benzyl-5-bromoindolin-2-one scaffold that connected through a hydrazone linker to a 4-arylthiazole (7a-d) or 4-methyl-5-(aryldiazenyl)thiazole (12a-e) moiety. The anticancer activity of all the reported indolin-2-one derivatives was assessed against breast (MCF-7) and lung (A-549) cancer cell lines. The 4-arylthiazole-bearing derivatives 7c and 7d revealed the best anticancer activity toward MCF-7 cells (IC50 = 7.17 ± 0.94 and 2.93 ± 0.47, respectively). Furthermore, the VEGFR-2 inhibitory activity for 7c and 7d was evaluated. Both molecules disclosed good inhibitory activity, and their IC50 values were equal to 0.728 µM and 0.503 µM, respectively. Additionally, the impacts of 7d on the cell cycle phases as well as on the levels of different apoptotic markers (caspase-3, caspase-9, Bax, and Bcl-2) were assessed. Molecular docking and dynamic simulations are carried out to explore the binding mode of 7d within the VEGFR-2 active site.

Age-based risk of end-stage kidney disease in patients with myelomeningocele

We aimed to quantify end-stage kidney disease (ESKD) risk after infancy in individuals with myelomeningocele (MMC) followed by urology in the modern medical era and to assess if ESKD risk was higher after surgery related to a hostile bladder. We retrospectively reviewed patients with MMC followed by urology at our institution born≥1972 (when clean intermittent catheterization was introduced) past 1 year of age (when mortality is highest, sometimes before establishing urology care). ESKD was defined as requiring permanent peritoneal/hemodialysis or renal transplantation. Early surgery related to hostile bladder included incontinent vesicostomy, bladder augmentation, detrusor Botulinum A toxin injection, ureteral reimplantation, or nephrectomy for recurrent urinary tract infections. Survival analysis and proportional hazards regression were used. Sensitivity analyses included: risk factor analysis with only vesicostomy, timing of surgery, including the entire population without minimal follow-up (n=1054) and only patients with≥5 years of follow-up (n=925). Overall, 1029 patients with MMC were followed for a median of 17.0 years (49% female, 76% shunted). Seven patients (0.7%) developed ESKD at a median 24.3 years old (5 hemodialysis, 1 peritoneal dialysis, 1 transplantation). On survival analysis, the ESKD risk was 0.3% at 20 years old and 2.1% at 30 years old (Figure). This was ∼100 times higher than the general population (0.003% by 21 years old, p<0.001). Patients who underwent early surgery for hostile bladder had higher ESKD risk (HR 8.3, p=0.001, 6% vs. 1.5% at 30 years). On exploratory analyses, gender, birth year, shunt status and wheelchair use were not associated with ESKD risk (p≥0.16). Thirty-year ESKD risk was 10% after early vesicostomy vs. 1.4% among children without one (p=0.001). Children undergoing bladder surgery between 1.5 and 5 years old had a higher risk of ESKD. No other statistically/clinically significant differences were noted. Patients with MMC remain at risk of progressive renal damage throughout life. We relied on the final binary ESKD outcome to quantify this risk, rather than imprecise glomerular filtration rate formulas. Analysis was limited by few people developing ESKD, inconsistent documentation of early urodynamic findings and indications for bladder-related surgery. While ESKD is relatively uncommon in the MMC population receiving routine urological care, affecting 2.1% of individuals in the first 3 decades, it is significantly higher than the general population. Children with poor bladder function are likely at high risk, underlining the need for routine urological care, particularly in adulthood.

Discrepancies between clinical diagnoses and autopsy findings: A comparative study conducted in South Africa.

The anatomical pathology autopsy serves several purposes, notably as a quality management tool for evaluation of accuracy in clinical diagnosis. Despite its value, for various reasons there has been an international decline in autopsies conducted. In the modern medical era, with all its advances in technology, diagnostic techniques and interventions, there is still a high discrepancy between clinical diagnoses and postmortem findings. To establish the discrepancies between clinical diagnoses and postmortem findings in anatomical pathology autopsies. A retrospective, descriptive study was conducted over the 4-year-period 2014 - 2017. The clinical diagnoses and postmortem findings of cases referred to the Department of Anatomical Pathology at the University of Pretoria, South Africa, were evaluated and compared using the modified Goldman criteria. A total of 288 cases qualified for the study and were evaluated. The gender distribution was 155 (53.8%) male and 133 (48.2%) female, with the majority of cases in the age group 19 - 60 years (mean 36.4). The majority of the cases were referred by internal medicine, followed by paediatrics. The most common cause of death in major missed diagnoses was pulmonary conditions. Of the cases, 115 (39.3%) had a major discrepancy and 62 (21.5%) a minor discrepancy. This study showed that there is still a high discrepancy between clinical diagnoses and postmortem findings, similar to studies conducted globally. The current COVID-19 pandemic may be a driver for revival of the anatomical pathology autopsy, and future studies are recommended to evaluate whether the decline can be reversed.

Antibacterial and Anti-Inflammatory Potential of Chinese Medicinal Herbs: Lonicerae flos, Lonicerae japonicae flos, Scutellaria baicalensis Georgi, and Forsythia suspensa

Chinese herbal medicine (CHM) represents a potent, safe, and efficacious reservoir of treatment options against an array of microbial infections and inflammatory diseases. It has a long history of positive clinical outcomes with minimal or no side effects while enhancing and bolstering the host's protection against infections. With its unique ability to prevent, treat, and manage a wide range of diseased conditions, CHM has been successfully practiced in China for thousands of years. In the modern medical era, where harsh therapeutic drugs and antimicrobial resistance (AMR) present a significant challenge, CHM warrants further exploration. The present review highlights and focuses on 4 major CHM-based herbs, that is, ( Lonicerae flos [ LF] , Lonicerae japonicae flos [ LJF] , Scutellaria baicalensis Georgi [ SBG] , and Forsythia suspensa [ FS]) in terms of their antibacterial and anti-inflammatory efficacies. A detailed literature survey was done by the team using a systematic electronic search from PubMed, Science Direct, Google Scholar, Research Gate, books, etc. This was followed by data collecting, pertinent data extraction, in-depth analysis, and composing the final review. Each herb has been discussed in detail describing its mechanism adopted and the bioactive components involved in alleviating bacterial infections and inflammatory damage. Further, proof of efficacy by detailing the major past studies and major findings has been discussed for each of the 4 herbs. This review will give the scientific community the opportunity to update their knowledge on the subject, which is crucial for heralding the process of bringing CHM-based medicines closer to clinical development given the area of alternative medicine's rapid advancements.

Dental Microstructural Imaging: From Conventional Radiology to In Vivo Confocal Microscopy

The innovative perspectives of the modern medical era aim to reach the highest performance and accuracy of therapeutic processes carried out for the evolution of diagnostic pathways. Digital planning and real-time diagnosis represent the hottest topics for researchers and clinicians in dentistry and oral medicine. To date, radiology is the gold-standard method for caries detection in the clinical setting. However, radiology poses a series of clinical limitations due to the use of ionizing radiation and its incapacity to recognize and detect enamel defects or early caries. In addition, radiology also presents issues surrounding its responsiveness to remineralizing agents and the microscopic gaps between the tooth and restorative treatments. To date, the evaluation of these conditions is only permitted ex vivo, with common methods in clinical practice not being applicable for establishing the actual condition of every case in every single patient. This work aims to develop state-of-the-art knowledge on conventional and unconventional innovative dental imaging techniques, focusing on those that not only promise to pursue the early and less invasive detection of dental disorders but also those that could be applied in clinical practice, with a particular interest in real-time in vivo confocal microscopy.

ANATOMICAL VARIATIONS IN ARTERIAL SUPPLY OF THUMB AND INDEX FINGER IN CADAVERIC HANDS

Human hand is highly evolved in terms of complexity and variations. In this modern medical era, vascular anatomy of the human hand has clinical importance in medical, surgical and radiological sciences. The intention of the current study is to determine the variations which occur as the radial artery branches thus making a contribution to the arterial supply of the index finger and the thumb. The study design was descriptive case series, carried out in the Department of Anatomy in King Edward Medical University from December 2018 to May 2019 on 30 cadaveric limbs. Vivisection of the cadaveric hands was performed following Cunningham’s Manual of practical anatomy. The origin and the course of RA, UA and MA were dissected and identified with further exploration of the blood supply of the index finger and the thumb. All details were entered in a predesigned proforma, and the dissected limbs were photographed. Data was analyzed to find the frequencies of superficial palmar arch as well as the arterial supply of thumb and index finger were also expressed in frequencies. Great variation was observed in the arterial supply to palmar aspect of index finger and thumb. Main contributing artery being radial artery in majority of cases through its common palmar or proper palmar branches arising from SPA or SPBRA. Ulnar artery and median artery were also observed to be supplying these areas in 6.6% and 3.3% cases respectively. The median artery when present was replacing the radial artery on palmar aspect of hand. The dorsum, however, was supplied by the princeps pollicis and the radialis indicis branches of radial artery in all the cases. We concluded that in about 1/3rd (11/30 are incomplete SPA) of our studied sample, arterial supply of the index finger and the thumb is highly dependent on radial artery and should any damage occur to it, vitality of these useful structures will be compromised.

Two factor authentication protocol for IoT based healthcare monitoring system.

In the last few years, technological advancement has led to the use of wearable body sensors for gathering patient information. Wireless body area networks played an essential role in the modern medical era. Through wearable body sensors, patient data are sent to medical professionals in real-time without any hindrance. This information moves through the public channel, and thus proper security and protection are needed because of its sensitiveness. Many authentication protocols proposed for solving these issues were neither secure nor cost-effective. This paper proposed an authentication protocol using certificateless cryptography for wireless body area networks to resolve the associated security concerns. A formal security analysis is done using the Burrows–Abadi–Needham logic shows that the proposed protocol is resilient against prevailing attacks. Additionally, we employ the Real-or-Random model for mathematical proof and Automated Verification Security Protocol and Analysis simulation tool for security analysis. A detailed comprehensive comparison with the existing protocols indicates that the proposed protocol is cost-effective with improved functionality.

Osteopontin in post-subarachnoid hemorrhage pathologies.

Rupture of intracranial aneurysms causes subarachnoid hemorrhage (SAH), of which the treatment remains the most difficult among cerebrovascular disorders even in this modern medical era. Following successful surgical ablation of ruptured intracranial aneurysms, other conditions may be encountered including delayed cerebral ischemia and chronic hydrocephalus, in addition to early brain injury. Osteopontin (OPN) is one of matricellular proteins that have cytokine-like effect on various cells and act as secretory extracellular matrix proteins between cells. The complexity of OPN functions is attributed to its several isoforms, cleavage sites and functional changes determined by its differing isoforms following various cleavages or other post-translational modifications. Notably, OPN functions beneficially or harmfully in accordance with the context of OPN upregulation. In the field of aneurysmal SAH, OPN has exerted neuroprotective effects against early brain injury and delayed cerebral ischemia by suppressing apoptosis of neurons, disruption of blood-brain barrier, and/or cerebrovascular constriction, while excessive and prolonged secretion of OPN can be harmful through the occurrence of chronic hydrocephalus requiring shunt surgery. This is a review article that is focused on OPN's potential roles in post-SAH pathologies.

EDITORIAL COMMENT

The field of sexual health in spina bifida (SB) has emerged rather recently as a direct result of a medical success story: The improved survival of people with SB in the modern medical era. Very much like the general population, adults with SB are sexual beings, sharing similar hopes, and aspirations.1 As the review by Hughes et al. indicates, sexual dysfunction among adults with SB is not only common and significant, but also poorly captured in the literature and inadequately understood. The trends are clear, underlining a need for clinically useful data.

Minimal prognostic significance of sentinel lymph node metastasis in patients with cT1\u20132 and cN0 breast cancer

BackgroundThe prognostic value of sentinel lymph node (SLN) metastases may be minimized by the limited disease burden of lymph node metastases and tailoring adjuvant therapy based on breast cancer biology. The aim of this study is to assess the prognostic significance of SLN metastasis in patients with cT1–2N0M0 breast cancer.Patients and methodsBetween January 2006 and December 2015, 582 patients underwent SLN biopsy for cT1–2N0M0 breast cancers. cN0 was essentially diagnosed by ultrasound sonography. The prognostic values of SLN metastases were retrospectively evaluated.ResultsAmong 582 patients with cT1–2N0M0 breast cancer, 111 patients (19.1%) were positive for SLN metastasis, including 39 cases (6.7%) of micrometastasis and 72 cases (12.4%) of macrometastases. The median size of SLN metastasis was 3.0 mm (range 0.2–16 mm, mean 4.1 mm). In log-rank test, presence of SLN metastasis was not associated with breast cancer recurrence (p = 0.21); 5-year and 10-year recurrence-free survival (RFS) were 93.0% and 96.5%, and 93.0% and 90.4% in the SLN-positive and SLN-negative groups, respectively. In the propensity score matching cohort (n = 178), there was no significant difference in RFS between the SLN-positive and SLN-negative groups (p = 0.90). In Cox regression analysis, a continuous value of Ki67 expression was a significant prognostic factor (HR 1.03; 95% CI 1.01–1.05, p = 0.017).ConclusionSLN metastasis has a minimal impact on RFS for patients with cT1–2N0M0 breast cancer in the modern medical era. A proliferation marker is a better factor for poor prognosis than the presence of SLN metastases in this population.

Predictors of Hypocalcaemia In Post Thyroidectomy Patients

Thyroid disorders and surgical management for thyroid disorders are more common in any surgeons day to day life. In this modern medical era for every 3 hours one paper was presented about thyroid disorders

English

English

Does Sex Bias Play a Role for Dissatisfied Patients With Hypothyroidism?

The current state of the diagnosis and management of thyroid disease cannot be separated from the larger context of women’s health for the following reasons: (1) the disproportionate incidence and prevalence of functional and structural thyroid diseases among women vs men; (2) the role of thyroid health on fertility, pregnancy, and postpartum; and (3) the challenge posed in managing the nonspecific symptoms of functional thyroid disease in the context of menopause. Here, we explore the hypothesis that sex bias has played a role in the management of thyroid diseases historically and has extended into the modern medical era. Once knowledge gaps that may have resulted from sex bias are recognized, we can strive to overcome this bias and develop better treatments to improve patient outcomes universally.

Virtual Reality in Cognitive and Perceptual Rehabilitation - A Promising Approach

In modern medical era, the paradigm of rehabilitation bench upon functional outcomes. The conventional approaches primarily dealing with physical issues in terms of sensory-motor deficits of patients with neurological disorders seem insufficient. Cognitive and perceptual rehabilitation is the one which enables the individual to utilize various sensory cues from environment together with its understanding, judgement and memory for achieving meaningful gains. It is important that the rehabilitation approaches do not underestimate the importance of this area of rehabilitation because cognitive and perceptual skills are, in a way, considered prerequisite skills to even physical performances.

Blood-Borne Revitalization of the Aged Brain.

In the modern medical era, more diverse and effective treatment options have translated to increased life expectancy. With this increased life span comes increased age-associated disease and the dire need to understand underlying causes so that therapies can be designed to mitigate the burden to health and the economy. Aging exacts a seemingly inevitable multisystem deterioration of function that acts as a risk factor for a variety of age-related disorders, including those that devastate organs of limited regenerative potential, such as the brain. Rather than studying the brain and mechanisms that govern its aging in isolation from other organ systems, an emerging approach is to understand the relatively unappreciated communication that exists between the brain and systemic environment. Revisiting classical methods of experimental physiology in animal models has uncovered surprising regenerative activity in young blood with translational implications for the aging liver, muscle, brain, and other organs. Soluble factors present in young or aged blood are sufficient to improve or impair cognitive function, respectively, suggesting an aging continuum of brain-relevant systemic factors. The age-associated plasma chemokine CCL11 has been shown to impair young brain function while GDF11 has been reported to increase the generation of neurons in aged mice. However, the identities of specific factors mediating memory-enhancing effects of young blood and their mechanisms of action are enigmatic. Here we review brain rejuvenation studies in the broader context of systemic rejuvenation research. We discuss putative mechanisms for blood-borne brain rejuvenation and suggest promising avenues for future research and development of therapies.

Is there an optimal strategy for pretransplant cardiovascular screening?

In Brief The commentator points out that despite increased understanding of noninvasive cardiac testing compared to angiography from the meta-analysis, we need data from the modern medical era in which statins and evolving cardiac biomarkers are widely used.

Alcohol Abuse, the Alveolar Macrophage and Pneumonia

AbstractAlcohol use, and misuse, has been a part of human culture for thousands of years. In the modern medical era, a great deal of attention has been justifiably focused on elucidating the mechanisms underlying the psychological and biological addiction to alcohol. However, a significant percentage, if not the majority, of alcohol-related morbidity and mortality occurs in individuals who do not meet the formal diagnostic criteria for alcohol use disorders. For example, many serious medical consequences of chronic alcohol ingestion can occur in individuals who do not have signs or symptoms of alcohol dependence. There is now clear evidence that even in otherwise healthy-appearing individuals who chronically consume excessive amounts of alcohol, alveolar macrophage immune capacity is impaired and, as a consequence, these individuals are at significantly increased risk of pneumonia. This brief review summarizes some of the key mechanisms underlying this phenomenon and proposes a hypothetical scheme by which alcohol interferes with zinc bioavailability within the alveolar space and thereby dampens macrophage function.