The Predictive Role of Serum Lipid Levels, p53 and ki-67, According to Molecular Subtypes in Breast Cancer: A Randomized Clinical Study.

Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a predictive potential in breast cancer is quite low. The evaluation of the lipid profile was carried out for the 142 patients who benefited from neoadjuvant therapy (NAC) in order to identify a potential predictive biomarker. The serological sample collection was performed sequentially according to a standardized protocol, pre-NAC, post-NAC and 6 months post-NAC after a 6-h pre-collection fast. We also investigated in the general group the presence or absence of the p53 mutation (TP53) and of the mitotic index ki-67, respectively, in relation to the molecular subtypes. The menopausal status, tumor size, family history, grading, Ki-67, p53 and LN metastases have a predictive nature regarding overall survival (OS) (p < 0.05), while for disease free survival (DFS), only tumor size, tumor grading, Ki-67 > 14, and p53+ are of predictive nature. The genetic and molecular analysis carried out in our group indicates that 71.67% have a Ki-67 score higher than 14%, and 39% of the patients have the positive P53 mutation. The multivariate analysis in the case of patients included in the TNBC subtype showed that the increased tumor volume (p = 0.002) and increased level of HDL (p = 0.004) represent predictive factors for the tumor response rate to NAC. High HDL-C levels before NAC and increased LDL-C levels after NAC were associated with the better treatment response in ER-positive and HER2+ breast cancer patients. Increased HDL-C values and tumor volume represent predictive factors as to the response rate to NAC in the case of patients included in the TNBC subtype. Regarding the ER+ and HER2+ subtypes, increased levels of HDL-C pre-NAC and increased levels of LDL-C post-NAC were associated with a better therapeutic response rate. Tumor grading, Ki-67, p53, and LN metastases have a predictive nature for OS, while tumor size, tumor grading, and Ki-67 > 14, and p53+ are predictive for DFS.

The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases.

Autoimmune dermatological diseases (AIDD) encompass a diverse group of disorders characterized by aberrant immune responses targeting the skin and its associated structures. In recent years, emerging evidence suggests a potential involvement of the renin-angiotensin system (RAS) in the pathogenesis and progression of these conditions. RAS is a multicomponent cascade, primarily known for its role in regulating blood pressure and fluid balance. All of the RAS components play an important role in controlling inflammation and other immune responses. Angiotensin II, the main effector, acts on two essential receptors: Angiotensin Receptor 1 and 2 (AT1R and AT2R). A disturbance in the axis can lead to many pathological processes, including autoimmune (AI) diseases. AT1R activation triggers diverse signaling cascades involved in inflammation, fibrosis and tissue remodeling. Experimental studies have demonstrated the presence of AT1R in various cutaneous cells and immune cells, further emphasizing its potential contribution to the AI processes in the skin. Furthermore, recent investigations have highlighted the role of other RAS components, beyond angiotensin-converting enzyme (ACE) and Ang II, that may contribute to the pathophysiology of AIDD. Alternative pathways involving ACE2, Ang receptors and Ang-(1-7) have been implicated in regulating immune responses and tissue homeostasis within the skin microenvironment. Understanding the intricate involvement of the RAS in AIDD may provide novel therapeutic opportunities. Targeting specific components of the RAS, such as angiotensin receptor blockers (ARBs), ACE inhibitors (ACEIs) or alternative RAS pathway modulators, could potentially ameliorate inflammatory responses, reduce tissue damage and lessen disease manifestations. Further research is warranted to outline the exact mechanisms underlying RAS-mediated immune dysregulation in AIDD. This abstract aims to provide a concise overview of the intricate interplay between the RAS and AIDD. Therefore, we elaborate a systematic review of the potential challenge of RAS in the AIDD, including psoriasis, systemic sclerosis, vitiligo, lupus erythematosus and many more.

Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?

Chronic delta hepatitis is a global health problem. Although a smaller percentage of chronic HBV-infected patients are coinfected with the hepatitis delta virus, these patients have a higher risk of an accelerated progression to fulminant "delta hepatitis", cirrhosis, hepatic decompensation, and hepatocellular carcinoma, putting a financial strain on the healthcare system and increasing the need for a liver transplant. Since its discovery, tremendous efforts have been directed toward understanding the intricate pathogenic mechanisms, discovering the complex viral replication process, the essential replicative intermediates, and cell division-mediated viral spread, which enables virion viability. The consideration of the interaction between HBV and HDV is crucial in the process of developing novel pharmaceuticals. Until just recently, interferon-based therapy was the only treatment available worldwide. This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor).

Is There a Time and a Place for the Gluten-Free Diet in Potential Celiac Disease?

Potential celiac disease (PCD) is characterized by the absence of villous atrophy on duodenal biopsies (Marsh 0 or 1) despite positive celiac serology and HLA DQ2 or DQ8 heterodimers. Recent epidemiological studies report that PCD represents one fifth of the total CD diagnoses. Compared to patients with CD, the majority of adult patients with PCD show lower rates of nutrient deficiencies and extraintestinal symptoms at diagnosis. Recommending a gluten-free diet (GFD) to PCD patients depends on whether they have symptoms or not. A significant clinical improvement is reported by symptomatic patients, but for asymptomatic PCD, diet implementation is still a matter of debate. Some questions remain to be answered: does PCD serve as an intermediary phase leading to the progression of true CD? Is it reasonable to hypothesize that PCD and active CD represent different manifestations of the same condition? Is there a potential for both underdiagnosis and overdiagnosis of CD in those who may have the condition? Additional research is required to address these inquiries and ascertain the specific subset of people with potential progression to overt CD, as well as to determine the potential advantages of early implementation of a GFD for these individuals. The investigation of risk factors in CD warrants examination of variables such as the timing of diagnosis, the genetic profile, the extent of gluten exposure, and the composition of the microbiome.

Emergency colectomy for massive rectal bleeding in a patient with well-controlled ulcerative colitis receiving Vedolizumab.

Ulcerative colitis (UC) is a chronic inflammatory condition, with a relapsing-remitting course. The case presented poses some valid questions regarding short-term and long-term management of patients with UC, and if the outcome (colectomy) could have been delayed or even prevented. Rectal bleeding is a cardinal symptom in patients with UC and it occurs among all patients during active disease. Massive rectal bleeding is an uncommon, but serious, complication of UC accounting for 0.1-1.4% of admissions. It is, nonetheless, noteworthy that instances of acute significant lower gastrointestinal bleeding accompanied by hemodynamic instability are infrequent. The rate of colectomy appears to be positively impacted by biological treatment. However, a refractory condition is still the primary reason for surgery, indicating a pressing need for new treatment approaches. Here we present the case of a young male patient who developed massive rectal bleeding and underwent emergent colectomy with ileostomy while having clinical and biological remission (normal calprotectin levels) at week 10 of Vedolizumab treatment.

Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease.

Aim: The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD). Background: Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment. Methods: The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016 and 2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis. Results: A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR. Conclusion: Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35 yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Risk Scores for Prediction of Major Cardiovascular Events in Non-Alcoholic Fatty Liver Disease: A No Man's Land?

Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.

Role of arterial hypertension and angiotensin II in chronic kidney disease (Review).

Chronic kidney disease (CKD) is a major public health issue, due to its effect on the quality of life of patients and by the huge costs incurred in treating this disease. It is an irreversible process, characterized by the progressive loss of functional nephrons. CKD ultimately requires the support of renal function by dialysis or even renal transplantation. It has a multiple etiology, but the most common causes remain arterial hypertension and diabetes. High arterial blood pressure affects the target organs (kidneys) and this leads to a vicious circle involved in maintaining high blood pressure. Arterial hypertension is closely related to the renal pathology of CKD. The result of excessive activation of the renin angiotensin system (RAS) is increased angiotensin II (Ang II), which acts upon the systemic circulation and especially upon the kidneys. The outcome is high blood pressure and also the stimulation of proinflammatory and profibrotic effects in the kidneys. Collectively these ultimately lead to CKD. The aim of this review was to provide a brief overview of the pathophysiological associations between CKD, arterial hypertension, and Ang II.

Twelve-Month Outcomes in Patients with Obesity Following Bariatric Surgery-A Single Centre Experience.

BACKGROUND: As obesity rates continue to rise worldwide, many surgeons consider bariatric procedures as a possible cure for the upcoming obesity pandemic. Excess weight represents a risk factor for multiple metabolic disorders, especially for type 2 diabetes mellitus (T2DM). There is a strong correlation between the two pathologies. The aim of this study is to highlight the safety and short-term results of laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB, laparoscopic gastric plication (LGP) and intragastric balloon (IGB) as methods used in the treatment of obesity. We followed the remission or amelioration of comorbidities, tracked metabolic parameters, weight loss curves and hoped to outline the profile of the obese patient in Romania. METHODS: The target population of this study was represented by patients (n = 488) with severe obesity who qualified for the metabolic surgery criteria. Starting from 2013 to 2019, patients underwent four types of bariatric procedures and were subsequently monitored over the course of 12 months in the 3rd Surgical Clinic at "Sf. Spiridon" Emergency Hospital Iași. Descriptive evaluation indicators, as well as those of analytical evaluation were used as statistical processing methods. RESULTS: A significant decrease in body weight was recorded during monitoring and was more pronounced for patients who underwent LSG and RYGB. T2DM was identified in 24.6% of patients. Partial remission of T2DM was present in 25.3% of cases, and total remission was identified in 61.4% of patients. Mean blood glucose levels, triglycerides, LDL and total cholesterol levels decreased significantly during monitoring. Vitamin D increased significantly regardless of the type of surgery performed, while mean levels of vitamin B12 decreased significantly during monitoring. Post-operative intraperitoneal bleeding occurred in 6 cases (1.22%) and a reintervention for haemostasis was required. CONCLUSIONS: All procedures performed were safe and effective methods of weight loss and improved associated comorbidities and metabolic parameters.

The Usefulness of Nanotechnology in Improving the Prognosis of Lung Cancer.

Lung cancer remains a major public health problem both in terms of incidence and specific mortality despite recent developments in terms of prevention, such as smoking reduction policies and clinical management advances. Better lung cancer prognosis could be achieved by early and accurate diagnosis and improved therapeutic interventions. Nanotechnology is a dynamic and fast-developing field; various medical applications have been developed and deployed, and more exist as proofs of concepts or experimental models. We aim to summarize current knowledge relevant to the use of nanotechnology in lung cancer management. Starting from the chemical structure-based classification of nanoparticles, we identify and review various practical implementations roughly organized as diagnostic or therapeutic in scope, ranging from innovative contrast agents to targeted drug carriers. Available data are presented starting with standards of practice and moving to highly experimental methods and proofs of concept; particularities, advantages, limits and future directions are explored, focusing on the potential impact on lung cancer clinical prognosis.

The RAAS Axis and SARS-CoV-2: From Oral to Systemic Manifestations.

One of the essential regulators of arterial blood pressure, the renin-angiotensin-aldosterone system (RAAS) seems to be one of the most complex mechanisms in the human body. Since the discovery of its key components and their actions, new substances and functions are still being unraveled. The main pathway begins with the secretion of renin in the kidney and culminates with the synthesis of angiotensin II (Ang II)-a strong vasoconstrictor-thanks to the angiotensin-converting enzyme (ACE). Research conducted in 2000 identified another enzyme, named ACE2, that converts Ang II into Ang-(1-7), a heptapeptide with opposing effects to those of Ang II: vasodilation and anti-inflammatory properties. This particular enzyme became of paramount importance during the last two decades, as a result of the confrontation of the human race with life-threatening epidemics. Multiple studies have been performed in order to uncover the link between ACE2 and human coronaviruses, the results of which we systemized in order to create an overview of the pathogenic mechanism. Human coronaviruses, such as SARS-CoV and SARS-CoV-2, attach to ACE2 via their spike proteins (S), causing the destruction of the enzyme. Because ACE2 limits the production of Ang II (by converting it into Ang-(1-7)), its destruction leads to a dysregulated inflammatory response. The purpose of this review is to decipher the complex pathophysiological mechanisms underlying the multiorgan complications (oral, cardiac, pulmonary, systemic) that appear as a result of the interaction of the SARS CoV-2 virus with the angiotensin-converting enzyme type 2.

Replacing the Burden of the Gluten Free Diet: Then, Now, and the Future.

Without a doubt, a majority of diseases are food-pattern-related. However, one disease stands out as an increasingly more common autoimmune-mediated enteropathy triggered by the ingestion of gluten. Celiac disease (CD) is an old disease, with changing clinical patterns, affecting any age, including infancy and adolescence, and becoming more frequent among the elderly. The gluten-free diet (GFD) has been the sole provider of clinical, serological, and histological improvement for patients with CD for more than seven decades. Nowadays, complete avoidance of dietary gluten is rarely possible because of the wide availability of wheat and other processed foods that contain even more gluten, to the detriment of gluten-free products. Undeniably, there is a definite need for replacing the burdensome GFD. An add-on therapy that could control the dietary transgressions and inadvertent gluten consumption that can possibly lead to overt CD should be considered while on GFD. Nevertheless, future drugs should be able to provide patients some freedom to self-manage CD and increase food independence, while actively reducing exposure and mucosal damage and alleviating GI symptoms. Numerous clinical trials assessing different molecules have already been performed with favorable outcomes, and hopefully they will soon be available for patient use.

Making a Comeback: Syphilitic Hepatitis in a Patient with Late Latent Syphilis-Case Report and Review of the Literature.

Treponema pallidum infection has emerged in recent years as an important community threat and burden to the health care system. Here, we report the case of a patient with cholestatic liver disease secondary to late latent syphilis. A 41 year-old male patient was referred to the clinic for assessment of an abnormal liver function panel. Ultrasound of the abdomen demonstrated an intense liver echogenicity, normal bile ducts, and no ascites. Virologic study revealed negative results for antibodies against common viral hepatitis and metabolic and autoimmune disease. The patient was tested for syphilis and a positive result was reported. The patient was diagnosed with late latent syphilis and syphilitic hepatitis and initiated benzathine penicillin at G 7.2 million units total, delivered as three doses of 2.4 million units intramuscular each at one-week intervals. He was assessed monthly and by the end of the sixth month, he had nonreactive VDRL (seroconversion), which confirmed recovery. Syphilitic hepatitis is an overlooked type of hepatitis and should be kept in mind as a differential diagnosis in an abnormal liver panel of uncertain etiology. Health care providers should be advised that higher levels of ALP may be the single landmark in cases of syphilitic hepatitis.

The Impact of Angiotensin-Converting Enzyme-2/Angiotensin 1-7 Axis in Establishing Severe COVID-19 Consequences.

The COVID-19 pandemic has put a tremendous stress on the medical community over the last two years. Managing the infection proved a lot more difficult after several research communities started to recognize the long-term effects of this disease. The cellular receptor for the virus was identified as angiotensin-converting enzyme-2 (ACE2), a molecule responsible for a wide array of processes, broadly variable amongst different organs. Angiotensin (Ang) 1-7 is the product of Ang II, a decaying reaction catalysed by ACE2. The effects observed after altering the level of ACE2 are essentially related to the variation of Ang 1-7. The renin-angiotensin-aldosterone system (RAAS) is comprised of two main branches, with ACE2 representing a crucial component of the protective part of the complex. The ACE2/Ang (1-7) axis is well represented in the testis, heart, brain, kidney, and intestine. Infection with the novel SARS-CoV-2 virus determines downregulation of ACE2 and interrupts the equilibrium between ACE and ACE2 in these organs. In this review, we highlight the link between the local effects of RAAS and the consequences of COVID-19 infection as they arise from observational studies.

SARS-CoV-2 Infection: What Is Currently Known about Homocysteine Involvement?

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world causing health, social and economic instability. The severity and prognosis of patients with SARS-CoV-2 infection are associated with the presence of comorbidities such as cardiovascular disease, hypertension, chronic lung disease, cerebrovascular disease, diabetes, chronic kidney disease, and malignancy. Thrombosis is one of the most serious complications that can occur in patients with COVID-19. Homocysteine is a non-proteinogenic α-amino acid considered a potential marker of thrombotic diseases. Our review aims to provide an updated analysis of the data on the involvement of homocysteine in COVID-19 to highlight the correlation of this amino acid with disease severity and the possible mechanisms by which it intervenes.

Vitamin D Deficiency in Both Oral and Systemic Manifestations in SARS-CoV-2 Infection: Updated Review.

The specialized literature emphasizes the fact that vitamin D has a potentially beneficial effect in the context of the current COVID-19 pandemic. The purpose of this article is to highlight the role of vitamin D, both prophylactic and curative, in the treatment of patients diagnosed with COVID-19. Even though its relevance is still unknown and causes various controversies, there is currently no specific treatment for patients diagnosed with COVID-19. There are various prevention strategies with new vaccination schedules, but additional randomized and clinical trials are still needed to combat this pandemic. In addition to the systemic manifestations of SARS-CoV-2 infection, oral manifestations of this disease have also been described in the literature. The etiology of oral manifestations associated with COVID-19 infection and vitamin D deficiency remains controversial. In the present studies, oral manifestations such as salivary gland infections, aphthae, erythema, gingivitis, ulcers, etc. have been reported. This is a new topic, and the prevalence of manifestations is described in only a few studies, which is inconsistent with the number of COVID-19 cases reported since the beginning of the pandemic. The clinical symptomatology in patients with current COVID-19 infection is polymorphic. Whether the oral manifestation is directly caused by SARS-CoV-2 or a secondary manifestation remains an important topic to analyze and discuss.