Great Advances In Medicine Research Articles

Vaccines: Do they have a role in orthopedic trauma?

Although vaccines have been hailed as one of the greatest advances in medicine based on their unparalleled cost-effectiveness in eradicating life-threatening infectious diseases, their role in orthopedic trauma-related infections is unclear. This is largely because vaccines are primarily made against pathogens that cause communicable diseases rather than opportunistic infections secondary to trauma, and most successful vaccines are against viruses rather than biofilm forming bacteria. Nonetheless, the tremendous costs to patients and healthcare systems warrant orthopedic trauma vaccine research, which has been a focal topic in recent international consensus meetings on musculoskeletal infection. This subject was also covered at the 2023 Osteosynthesis and Trauma Care Foundation (OTCF) meeting in Rome, Italy, and the purpose of this supplement article is to (1) highlight the osteoimmunology, animal models, translational research and clinical pilots that were discussed, (2) the proposed future directions that could lead to diagnostics and prognostics that are critically needed for evidence-based decision making, and (3) vaccines and passive-immunization strategies that could potentially be utilized to treat patients with orthopedic infections.

Comparative Evaluation of Antimicrobial Activity of Cotton Balls Incorporated With Musa paradisiaca and Chitosan: An In Vitro Study.

Introduction: Antibiotics are one of the great advances in medicine. But overusing them has led to resistant bacteria (bacteria that are harder to treat). The current study foresees better non-toxic antimicrobial substances (conventional antibiotics) that insist to consider medicinal plants and animal-derived products, which have better antibiotics without any side effects. The goal of this in-vitro study was to evaluate the antimicrobial activity of cotton balls incorporated with Musa paradisiaca and chitosan.Materials and methods: Musa paradisiaca, chitosan, and gentamicin-reinforced cotton balls were considered in three groups namely Group 1, Group 2, and Group 3, which tested against the strains of Staphylococcus aureus, Escherichia coli, Actinomyces israelii, Streptococcus mutans, andBacteroides fragilis. For the present study, pre-sterilized cotton balls were taken and then soaked with Banana peel extract and soluble chitosan solution at different concentrations of 500 μg/ml, 250 μg/ml, 100 μg/ml, and 50 μg/ml under aseptic conditions and were dried at 50° overnight. The same incorporation method was followed for a 10mg/ml concentration of gentamicin, which was used as a positive control group.Results: In this current study, the banana peel extract, soluble chitosan, and gentamicin exhibited antimicrobial activity against all the tested microorganisms. In the well diffusion method, at the concentration of 500 μg/ml and 250 μg/ml, chitosan and banana peel extract were comparatively better than the positive control group (gentamicin) at a higher concentration of 10 mg/ml.Conclusion: From the results of the present study, a lower concentration of the testing group (soluble chitosan and banana peel extract) exhibited a better effect when compared to a higher concentration of gentamicin. Hence, chitosan and banana peel extract impregnated cotton could be preferred for routine clinical scenarios like wounds, extractions sockets, and during any short intraoperative surgical procedures periodontal surgery, where it can provide maximal antimicrobial effects without the side effects of antibiotics.

Utility of Red Cell Distribution Width (RDW) as a Noninvasive Biomarker for the Diagnosis of Acute Appendicitis: A Systematic Review and Meta-Analysis of 5222 Cases.

Background: Despite great advances in medicine, numerous available laboratory markers, and radiological imaging, the diagnosis of acute appendicitis (AA) in some cases still remains controversial and challenging for clinicians. Because of that, clinicians are still looking for an ideal marker that would be specific to AA. The red blood cell distribution width (RDW) has been recently investigated in several studies as a potential biomarker for AA. The aim of this systematic review and meta-analysis was to systematically summarize and compare all relevant data on RDW as a diagnostic biomarker for AA. Methods: This systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Scientific databases (PubMed, Scopus, Web of Science, and Excerpta Medica database—EMBASE) were systematically searched for relevant comparative studies by two independent researches using keywords ((red cell distribution width) OR rdw) AND (appendicitis). An independent assessment of the methodological quality was performed by two authors using the Downs and Black scale. RevMan 5.4 software was used to perform the meta-analysis. Results: Fifteen studies were included in the final meta-analysis; the majority of the studies was retrospective. Nine studies compared the RDW values between AA and non-AA; four studies compared the same between AA and healthy controls, while two studies compared the RDW values among all three groups. The estimated heterogeneity among the studies for all outcome was statistically significant (I2 = 92–99%, p < 0.00001). The pooling the data demonstrated no statistically significant difference in the RDW values (weighted mean difference (WMD) = 0.03, 95% CI = (−0.46, 0.52), p = 0.91) between AA and healthy controls as well as between AA and non-AA cases (WMD = 0.23, 95%CI = (–0.19, 0.65), p = 0.28). A separate subanalysis was performed to evaluate the utility of this biomarker for the pediatric age group. Pooling the data demonstrated no significant difference among the AA and non-AA groups in terms of the RDW values (WMD = 0.99, 95% CI = (–0.35, 2.33), p = 0.15). Conclusion: The RDW value difference demonstrated no statistically significant difference in AA versus healthy individuals and AA versus non-AA individuals. At the moment, there is no evidence of RDW utility in diagnostic testing of AA. Further research with prospective, multicenter studies and studies targeting special patient groups with a large sample size are needed in this field.

NLRP3 Inflammasome in Vascular Disease: A Recurrent Villain to Combat Pharmacologically.

Despite the great advances in medicine, mortality from cardiovascular diseases keeps on growing. This tendency is not likely to change considering the pandemic proportions of obesity and diabetes. Besides, the global population is more aged as life expectancy increases, and vascular aging plays a key role in the increased risk of vascular disease. In light of recent trials, namely the CANTOS study, showing the enormous potential of anti-inflammatory therapies and in particular those targeted to IL-1β, a change in therapeutical management of cardiovascular diseases is coming about. The NLRP3 inflammasome is a multiprotein complex that assembles to engage the innate immune defense by processing the maturation of pro-inflammatory cytokines IL-1β and IL-18. Substantial evidence has positioned the NLRP3 inflammasome at the center of vascular disease progression, with a particular significance in the context of aging and the low-grade chronic inflammation associated (inflammaging). Therefore, pharmacological blockade of the NLRP3 inflammasome and its end products has arisen as an extremely promising tool to battle vascular disease. In this review, we discuss the mechanisms by which the NLRP3 inflammasome contributes to vascular disease, with particular attention to the consequences of aging, and we enumerate the therapeutic options available to combat this recurrent villain.

The Forgotten Member of Patient Selection Committees: The US Constitution.

The Forgotten Member of Patient Selection Committees: The US Constitution.

Adropin and irisin in arterial hypertension, diabetes mellitus and chronic kidney disease.

Despite great advances in medicine, the proper treatment of arterial hypertension (AH), diabetes mellitus (DM) and chronic kidney disease (CKD) remains a major challenge. Untreated, undiagnosed AH or DM may lead to the development of CKD and consequently to the occurrence of cardiovascular events. Adropin and irisin are newly discovered proteins which may play a role in the development and progression of the chronic diseases mentioned above. Endothelium dysfunction could be a bonding point. The following review paper focuses on adropin and irisin concentrations and their correlations in AH, DM and CKD. Lower adropin concentrations have been measured in patients with primary AH when compared to healthy volunteers. Irisin has reduced blood pressure on nitric oxide (NO)-dependent pathways in experimental studies; a negative correlation between irisin and blood pressure values has also been observed in preeclamptic women. Irisin also plays a role in insulin sensitivity and metabolic disorders. Lower irisin levels have been observed in patients with DM type 2 in comparison to a nondiabetic control group. It is also lower in the serum of pregnant women with gestational DM. A negative correlation between irisin and estimated glomerular filtration rate (EGFR) has also been noted. Adropin and irisin are newly described myokines measured in human plasma in healthy and disease status. Their exact function has not been specified yet and requires further studies.

Straddling medical specialties: should we have more comprehensive advanced training?

Over careers spanning 35 years each, we have witnessed great advances in medicine especially in genetics, imaging, immunotherapies and targeted cancer therapies. Our respective specialties of endocrinology and medical oncology have come to overlap significantly necessitating better communication and skills across both specialties. We will highlight common scenarios that straddle endocrinology and medical oncology. The same broad issues apply to other closely related specialties, albeit with different clinical challenges. At present, we see expensive and inefficient cross-referrals to other subspecialists or sometimes no referral at all, leading to significant clinical omissions. Opportunities for dual advanced training, or for more comprehensive single advanced training could more efficiently lead to enhanced patient care and communication.

Pathway to the Papanicolaou smear: The development of cervical cytology in twentieth-century America and implications in the present day

George Papanicolaou, a Greek immigrant and cytopathologist, was responsible for what is now colloquially known as the “Pap smear”—undoubtedly one of the greatest advances in medicine and public health of the last century. However, his landmark research on the development of cervical cytology for the detection of precancerous lesions of the cervix (“New Cancer Diagnosis,” 1928) made a rather inauspicious debut in an unlikely venue: John Harvey Kellogg's Third Race Betterment Conference—a meeting devoted to the furtherance of the concept and implementation of eugenics. Herein, we discuss the stark juxtaposition of Papanicolaou's landmark discovery amid the pseudoscience of the third Race Betterment Conference. We discuss the latency of Papnicolaou's discovery–its potential implications unrealized–until co-publication with Herbert Traut, which catapulted Papanicolaou's research to the scientific foreground. This gave rise to public health initiatives aimed at establishing the Pap smear as a screening tool. We further delineate the progress made in recent decades with the identification of HPV as the etiological agent for cervical cancer, and the subsequent development of the HPV vaccine, and discuss ongoing research in the present day. In this way, we hope to provide a background and historical context for the development of the Pap smear.

The Team Based Biopsychosocial Model: Having a Clinical Ethicist as a Facilitator and a Bridge Between Teams.

The biopsychosocial model is characterized by the systematic consideration of biological, psychological, and social factors and their complex interactions in understanding health, illness, and health care delivery. This model opposes the biomedical model, which is the foundation of most current clinical practice. In the biomedical model, quest for evidence based medicine, the patient is reduced to molecules, genes, organelles, systems, diseases, etc. This reduction has brought great advances in medicine, but it lacks a holistic view of the person. To solve the problem, we propose an early team based approach where the primary care physician leads a group of people that can help her/him address the psychosocial issues while she/he attends to the biomedical issues. This article addresses one case where the clinical ethicist facilitating a team based biopsychosocial model for the care of a patient worked as a bridge between the primary team, the critical care team, and the psychosocial team to advance the argument that good communication among the groups can lead to a true biopsychosocial model where the collaboration of the social worker, psychologist, chaplain, ethicist and the different medical teams can improve the overall patient experience.

The Carbapenems Issue

The development of antibiotics remains one of the great advances in medicine. Antibiotics have saved countless lives. Unfortunately, the widespread use of antimicrobials has led to the development of antimicrobial resistance. Antibiotic resistance is an important concern for public health; it is associated with poor outcomes. Carbapenems, members of the β-lactam class of antibiotics, have the broadest spectrum of antimicrobial activity. Carbapenem resistance is one of the toughest challenges in infectious diseases; it is associated with high mortality and is seen more often now due to the proliferation of multi-drug resistant bacteria. Multiple genes that cause carbapenem resistance have been identified. Resistance transmission is usually nosocomial, but community-acquired infections with resistance have been reported. Early recognition of high risk patients for multi-drug resistant infections is fundamental for adequate management. The rational use of antibiotics is required to prevent the spread of antimicrobial resistance; this requires multidisciplinary efforts among clinicians, Infection Control departments, and Antimicrobial Stewardship programs.

Calidad de vida: un aspecto olvidado en el paciente con hemofilia

La hemofilia es una patología derivada de la deficiencia heredada de factores de la coagulación, comúnmente ligada al cromosoma X que presenta diferentes tipos de hemorragias. Clínicamente la hemofilia se clasifica según la deficiencia del factor de coagulación específico y su cuadro clínico se compone de episodios hemorrágicos y de las complicaciones de los mismos. A pesar de los grandes avances en la medicina, la hemofilia persiste como una enfermedad crónica asociada a importantes secuelas que generan un impacto sobre la calidad de vida. A nivel mundial, 1/10.000 hombres está afectado por esta enfermedad, lo que a nivel local se traduce como 3,8 a 4,3 afectados por cada 100.000 habitantes. La Calidad de vida es un importante concepto que se debe tener en cuenta en el abordaje integral de pacientes que Hemofilia ya que los factores biológicos relacionados con esta patología tienen gran impacto en el deterioro físico, social y psicológico de los pacientes afectados y, obviar su valoración significa perpetuar el deterioro generado por la enfermedad. La medición de la calidad de vida de estos pacientes debe ser de carácter rutinario en la práctica clínica mediante el uso de herramientas internacionalmente validadas.

A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa - case report and literature review

BackgroundEpidermolysis bullosa (EB) constitutes a heterogenous group of rare multisystem genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EB manifestation is not only limited to the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract and upper gastrointestinal tract. The presence of particular symptoms is directly determined by a type of altered skin protein. Gastrointestinal manifestation of EB is most commonly reflected by esophageal stenosis due to recurrent esophageal blistering, followed by consequent scarring.Case presentationHere we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland.ConclusionsManagement of an esophageal stricture in such circumstances is based on endoscopic dilatation. However, in most severe cases, placement of a gastrostomy tube is required. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.

Tuberculous meningoencephalitis in a patient with human immunodeficiency virus infection

Background: Tuberculous meningoencephalitis is an infrequent disease. The diagnosis given the poor specificity of complementary tests is very difficult, as well as the treatment in patients infected with the human immunodeficiency virus doing antiretrovirals. Case Summary: We present the case of a 33-year-old man with history of intravenous drug user, hepatitis B and HIV coinfection, lymph node tuberculosis and meningitis due to Cryptococcus Neoformans; was admitted to the Emergency Department due to altered state of consciousness and neurological focality, with a week of evolution. In the diagnostic process, several etiological hypotheses were discarded and several lines of empirical treatment were instituted, until some evidence was obtained. Multiple imaging tests were performed and the progression of the CT scan was the one that ended up confirming the diagnosis. Conclusion: Despite the great advances in medicine, Tuberculosis seems to be the heel of Achilles, where, having the certainty of the diagnosis remains, as in the case presented, tremendously difficult. We have laboratory, microbiological, imaging and even biopsy exams, and sometimes it is not enough to achieve the diagnosis with evidence. In the case presented, the only evidence was obtained due to the evolution of the lesions, which should never be a limiting factor for the initiation of treatment, due to the serious consequences that the non-implementation of treatment may have.

Chapter 22 - Genetics of neurodegenerative diseases: an overview

Genetic factors are central to the etiology of neurodegeneration, both as monogenic causes of heritable disease and as modifiers of susceptibility to complex, sporadic disorders. Over the last two decades, the identification of disease genes and risk loci has led to some of the greatest advances in medicine and invaluable insights into pathogenic mechanisms and disease pathways. Large-scale research efforts, novel study designs, and advances in methodology are rapidly expanding our understanding of the genome and the genetic architecture of neurodegenerative disease. Here, we review major developments in the field to date, highlighting overarching historic trends and general insights. Monogenic neurodegenerative diseases are discussed from the perspectives of both rare Mendelian forms of common disorders, such as Alzheimer disease and Parkinson disease, and heterogeneous heritable conditions, including ataxias and spastic paraplegias. Next, we summarize the experiences from investigations of complex neurodegenerative disorders, including genomewide association studies. In the final section, we reflect upon the limitations of current findings and outline important future directions. Genetics plays an essential role in translational research, ultimately aiming to develop novel disease-modifying therapies for neurodegenerative disorders. We anticipate that individual genetic profiling will also be increasingly relevant in a clinical context, with implications for patient care in line with the proposed ideal of personalized medicine.

Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway

Obesity may cause several metabolic complications, including insulin resistance and type 2 diabetes mellitus. Despite great advances in medicine, people still keep exploring novel and effective drugs for treatment of obesity and insulin resistance. The aim of this study was to survey if baicalin might ameliorate obesity-induced insulin resistance and to explore its signal mechanisms in skeletal muscles of mice. Diet-induced obese (DIO) mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and C2C12 myotubes were treated with 100, 200, 400 μM baicalin for 12 h in this study. Then insulin resistance indexes and insulin signal protein levels in skeletal muscles were examined. We discovered that administration of baicalin decreased food intake, body weight, HOMA-IR and NT-PGC-1α levels, but enhanced GLUT4, PGC-1α, pP38MAPK, pAKT and pAS160 contents, as well as GLUT4 mRNA, PGC-1α mRNA, PPARγ mRNA, GLUT1 mRNA expression in skeletal muscles of obese mice and myotubes of C2C12 cells, and reversed high fat diet-induced glucose and insulin intolerance, hyperglycemia and insulin resistance in the mice. These results suggest that baicalin is a powerful and promising agent for treatment of obesity and insulin resistance via Akt/AS160/GLUT4 and P38MAPK/PGC1α/GLUT4 pathway.

Fifty years of phenylketonuria newborn screening — A great success for many, but what about the rest?

Guthrie's landmark discovery and the subsequent implementation of the first newborn screening programs for phenylketonuria (PKU) and other inherited errors of metabolism (IEM) could be – in a 50year retrospective – easily considered among the greatest advances in medicine. They have not just improved the quality of hundreds of thousands of lives, but also transformed our understanding and approach to PKU and IEM in general. However, according to the available albeit very scarce data, many countries and regions seem not to share the benefits of the last 50years of development. Many of them have not yet introduced the newborn screening for PKU or face significant problems in its implementation. In addition, the issue seems to be underrated by the relevant professional forums. Action to improve the current situation should urgently be taken.

Síndrome de Romberg: uma série de casos

INTRODUÇÃO: A síndrome de Romberg é uma moléstia descrita há mais de um século e, nesse período, recebeu várias denominações. É caracterizada por lenta e progressiva atrofia dos tecidos de uma hemiface, podendo acometer todos os tecidos e apresentar, também, manifestações neurológicas e oculares. O objetivo deste estudo é relatar série de casos de pacientes com atrofia hemifacial progressiva, abordando as opções terapêuticas individualizadas para cada caso. MÉTODO: Foi realizado estudo retrospectivo, descritivo e analítico de pacientes atendidos nos ambulatórios de Cirurgia Plástica no Hospital de Clínicas da Universidade Federal do Paraná e no Centro de Atendimento Integral ao Fissurado Lábio Palatal (CAIF), em Curitiba, PR, Brasil. RESULTADOS: Foram analisados 13 pacientes, sendo 10 (76,9%) do sexo feminino e 3 (23,1%) do sexo masculino. A idade de início dos sintomas variou de 2 anos a 15 anos. A primeira consulta ocorreu, em média, aos 11,7 anos. A hemiface mais frequentemente afetada foi a esquerda. Sete (53,8%) pacientes foram submetidos a cirurgia. CONCLUSÕES: A síndrome de Romberg é uma entidade rara, devastadora na aparência facial, que tem sido muito estudada. Apesar dos grandes avanços da medicina, a definição de sua etiologia e um tratamento direcionado a sua causa ainda são apenas um desejo.

Working with Industry: What Is the Conflict?

The relationship between medicine and industry has always shared conflicts. There are obvious benefits to these relationships and inherent potential risks. The collaboration between academic medicine and industry has allowed for great advances in medicine in terms of drug, technology, and procedural developments. However, for-profit companies' interests may not align with those of academic universities. Companies tend to undertake research when the results of such work leads to company profits or enhances their reputation, and not solely for greater scientific understanding. In this article, the author reviews the types of conflicts of interest, the role of industry-sponsored trials, the adoption of new technologies from industry, and the role of industry with our medical society.

Predicting the cost-effectiveness of total hip and knee replacement

The aim of this study was to perform a cost–utility analysis of total hip (THR) and knee replacement (TKR). Arthritis is a disabling condition that leads to long-term deterioration in quality of life. Total joint replacement, despite being one of the greatest advances in medicine of the modern era, has recently come under scrutiny. The National Health Service (NHS) has competing demands, and resource allocation is challenging in times of economic restraint. Patients who underwent THR (n = 348) or TKR (n = 323) between January and July 2010 in one Scottish region were entered into a prospective arthroplasty database. A health–utility score was derived from the EuroQol (EQ-5D) score pre-operatively and at one year, and was combined with individual life expectancy to derive the quality-adjusted life years (QALYs) gained. Two-way analysis of variance was used to compare QALYs gained between procedures, while controlling for baseline differences. The number of QALYs gained was higher after THR than after TKR (6.5 vs 4.0 years, p &lt; 0.001). The cost per QALY for THR was £1372 compared with £2101 for TKR. The predictors of an increase in QALYs gained were poorer health before surgery (p &lt; 0.001) and younger age (p &lt; 0.001). General health (EQ-5D VAS) showed greater improvement after THR than after TKR (p &lt; 0.001). This study provides up-to-date cost-effectiveness data for total joint replacement. THR and TKR are extremely effective both clinically and in terms of cost effectiveness, with costs that compare favourably to those of other medical interventions. Cite this article: Bone Joint J 2013;95-B:115–21.

Transplant tolerance: new insights and strategies for long-term allograft acceptance.

One of the greatest advances in medicine during the past century is the introduction of organ transplantation. This therapeutic strategy designed to treat organ failure and organ dysfunction allows to prolong the survival of many patients that are faced with no other treatment option. Today, organ transplantation between genetically dissimilar individuals (allogeneic grafting) is a procedure widely used as a therapeutic alternative in cases of organ failure, hematological disease treatment, and some malignancies. Despite the potential of organ transplantation, the administration of immunosuppressive drugs required for allograft acceptance induces severe immunosuppression in transplanted patients, which leads to serious side effects such as infection with opportunistic pathogens and the occurrence of neoplasias, in addition to the known intrinsic toxicity of these drugs. To solve this setback in allotransplantation, researchers have focused on manipulating the immune response in order to create a state of tolerance rather than unspecific immunosuppression. Here, we describe the different treatments and some of the novel immunotherapeutic strategies undertaken to induce transplantation tolerance.