Pioglitazone and asthma: a review of current evidence.

OBJECTIVE: This review aims to present existing evidence on the impact of pioglitazone, a thiazolidinedione class anti-diabetic drug, on asthma control and lung function, providing a comprehensive understanding of its potential as a treatment for asthma. DATA SOURCES: The review draws upon data from preclinical animal studies and clinical trials investigating the effects of pioglitazone on asthma, focusing on its role in reducing airway inflammation, hyperreactivity, and remodeling, and its impact on pulmonary function. STUDY SELECTIONS: Relevant studies were selected based on their examination of pioglitazone's therapeutic effects in asthma, including both animal models and clinical trials involving human asthma patients. RESULTS: Animal studies have suggested that pioglitazone could alleviate inflammation, airway hyperreactivity, and airway remodeling, thereby improving pulmonary function in asthma. However, clinical trials have not demonstrated significant therapeutic benefits, with minimal improvements observed in asthma control and lung function, and the presence of notable side effects. CONCLUSION: Despite promising preclinical data, the efficacy of pioglitazone in treating human asthma remains unproven, with safety concerns and limited clinical benefits observed in trials. Further research is needed to assess the safety and effectiveness of pioglitazone in asthma treatment and to explore its impact on other inflammatory mechanisms.

Cellular senescence and hepatitis B-related hepatocellular carcinoma: An intriguing link.

Chronic hepatitis B is mainly responsible for the morbidity and mortality from hepatitis B virus (HBV)-related complications, including hepatocellular carcinoma (HCC) and decompensated cirrhosis. Hepatocellular carcinoma remains the main challenge in the management of not only undiagnosed and/or untreated but also diagnosed and treated patients with chronic HBV infection, as its incidence decreases but is not eliminated even after many years of effective anti-HBV therapy. The exact mechanisms used by HBV to cause malignant transformation remain uncertain, although much of the available data are in favour of a pathogenetic role of HBx protein. Senescence is a cellular state, in which cells lose their ability to proliferate. This biological mechanism may function in a dual mode, namely being both cancer-protective as a result of reduced cellular proliferation, but also cancer-enhancing as a result of modulation of the tissular microenvironment by immune cells during persistent accumulation of senescent cells. Protein X of HBV protein exhibits many similarities in terms of the implemented mechanisms of action and pathways related to the biological process of cellular senescence. Concurrently, insufficient clearance of both senescent and precancerous hepatocytes combined with inadequate immune surveillance as a result of immunosenescence caused by chronic HBV infection may lead to hepatocarcinogenesis. Thus, the effect of HBV seems to be critical as a connecting link between cellular senescence and development of HCC. An ongoing research is underway towards identifying and validating markers of hepatocyte senescence, which could improve the landscape for evaluation of chronic liver disease, thereby providing valuable information in terms of HBV-related carcinogenesis.

Gastric neuroendocrine tumour, atrophic gastritis and autoimmune haemolytic anaemia: a case report and review.

Gastric neuroendocrine tumours are rare. We describe a unique case of a 66-year-old male patient who presented with shortness of breath and malaise, eventually attributed to severe autoimmune haemolysis in the context of atrophic gastritis and multiple type-1 gastric neuroendocrine tumours. The patient had also positive anti-cardiolipin antibodies. A favourable outcome was attained with corticosteroids plus subtotal gastrectomy for the treatment of the underlying neoplastic disease. This case illustrates that the differential diagnosis of any associated causes of autoimmune haemolytic anaemia can be challenging, and may extend to unexpected conditions.

Metformin in Type 2 Diabetes: Evidence for its Beneficial Effects on Frailty and Sarcopenia.

This narrative review aimed to discuss the potential interplay among frailty syndrome, sarcopenia and metformin in type 2 diabetes mellitus (T2DM). There is emerging evidence on the potential protective role of metformin on both frailty and sarcopenia. However, results are not always consistent. Thus, further research is needed to provide a definitive answer on any role of metformin in improving frailty and/or sarcopenia in T2DM.

Folic Acid and Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) remain a major cause of morbidity. This narrative mini-review aimed to investigate the potential role of folic acid (FA) in DFUs. Individuals with DFUs exhibit lower levels of FA and lower daily intake, compared to those without DFUs. There is preliminary evidence that FA administration may contribute to improved DFUs healing. In this context, regular evaluation of dietary FA intake may prove important towards reduction or even prevention of DFUs. However, data are still limited and further research is required to enable definitive conclusions and any recommendations.

The Role of Folic Acid in SARS-CoV-2 Infection: An Intriguing Linkage under Investigation.

BACKGROUND: SARS-CoV-2 is a life-threatening RNA virus that may cause an acute respiratory syndrome associated with extremely high morbidity and mortality rates. Folic acid (FA), also known as folate, is an essential vitamin vital for human homeostasis, participating in many biochemical pathways, and its deficiency has been associated with viral infection vulnerability. In this review, we investigated the association between FA intake and SARS-CoV-2 infection, along with the existence of any potential impact of FA on the health outcome of patients suffering from this new viral infection. METHODS: Studies included were patients' and in silico and molecular docking studies. RESULTS: Data from in silico studies and molecular docking support that FA inhibits SARS-CoV-2 entry into the host and viral replication, binding at essential residues. Accordingly, in patients' studies, a protective role of FA supplementation against SARS-CoV-2 infection is indicated. However, contradictory data from observational studies indicate that FA supplementation, often linked to deficits during systemic inflammation due to SARS-CoV-2, increases the risk of post-infection mortality. CONCLUSIONS: Future randomized controlled trial studies, including the FA pharmacological group, are needed to better understand the role of FA as a potential protective or mortality risk indicator in COVID-19 patients.

Sarcopenia and Tuberculosis: Is There Any Connection?

BACKGROUND: Tuberculosis (TB) infection is a life-threatening infection caused by certain bacteria belonging to the Mycobacterium tuberculosis complex. More than 10 million subjects are newly sick from this infection every year globally. At the same time, TB is quite prevalent among subjects who come from lower socioeconomic layers of general population, and marginalized sections and areas. Sarcopenia is a muscle disease that derives from adverse muscle alterations and is related to the loss of muscle strength and mass. It is a major medical issue due to its increased adverse outcomes including falls, functional decline, frailty, hospitalizations, increased mortality, and healthcare costs. METHODS: This study examined the potential interplay between the TB infection and sarcopenia through conducting a non-systematic review of the current literature. RESULTS: It has been recorded that the prevalence of sarcopenia among TB survivors is high, whilst the danger of TB among the elderly increases with sarcopenia and physical inactivity. Nevertheless, sufficient protein and total energy intake are associated with a low risk of sarcopenia in TB survivors. CONCLUSIONS: Further studies are needed to validate these findings and shed more light on the upcoming different aspects of this intriguing association.

B-Blockers in Liver Cirrhosis: A Wonder Drug for Every Stage of Portal Hypertension? A Narrative Review.

In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors' proposals on the use of NSBBs concerning the severity of liver disease and the patient's performance status.

Coccygeal Disc Disease as a Possible Cause of Coccygodynia.

OBJECTIVE: The aim of the present study was to describe the causes involved in the pathophysiology of coccydynia, emerging from the coccyx or the anatomical tailbone region. CASE REPORT: We present the case of a 64-year-old man with pain in the coccyx and numbness in the perianal area. After clinical examination and imaging evaluation, including plain X-rays and magnetic resonance, coccygeal disc disease was identified. Other findings, such as tumor and fracture were excluded. We decided to undertake conservative management and the pain was eventually relieved. This is the first case report of coccygodynia and perianal numbness attributed to coccygeal disc disease. CONLCUSION: Although there is no standard treatment, coexisting coccygeal disc disease should be always taken into account, with clinical and imaging examinations being considered of major importance to establish both medical diagnosis and treatment.

Primary Health Care: Our Experience From an Urban Primary Health Care Center in Greece.

This observational study reported patient data derived from the emergency files of a primary health care (PHC) center in Greece, with the aim of providing potential solutions for a well-organized, well-structured, and effective social healthcare system. This series was conducted at a single urban PHC center in Greece between August 2017 and March 2020. A total of 83,592 patient visits were registered. The mean patient age was 42.5 years (range: three months to 93 years). Demographics, presenting complaints, and the need for patients who visited the healthcare center to be referred to tertiary hospitals were examined. Further perspectives and future strategies to strengthen the national PHC system were addressed. The most common reasons for visits were pathological (33.6%), followed by general surgery (21.2%) and orthopedics (18.1%). Pediatric conditions accounted for 12% of visits, cardiological conditions accounted for 8.6%, and dental problems accounted for 6.8%. The majority of the patients (n = 81,317, 97.3%) were managed within the health center, and only 2.7% of cases (n = 2275) needed to be referred to a secondary or tertiary healthcare structure. Reasons for patient referral included the severity or complexity of the patient's situation, lack of a specific medical specialty, and the unavailability of overnight laboratory tests. The PHC center remains the cornerstone of a high-quality healthcare system. A well-structured PHC unit can improve health outcomes and decongest secondary and tertiary health care.

Vitamin E and diabetic foot ulcers.

This narrative mini-review discusses vitamin E levels in subjects with diabetic foot ulcers (DFUs). Vitamin E may be reduced in subjects with DFUs, but this finding is inconsistent. Its administration appears to benefit patients with DM, delaying the onset of complications, including DFU. There is also evidence that it may promote DFU healing. Nonetheless, further studies are required to confirm these promising results and estimate vitamin E administration's cost-effectiveness.

Zinc Levels and Diabetic Foot Ulcers: A Mini Review.

The aim of this nonsystematic mini review was to discuss serum levels of zinc in subjects with diabetic foot ulcers (DFUs). Most studies have reported low zinc levels in subjects with DFUs. Furthermore, there is some evidence that oral zinc supplementation may have a positive and beneficial impact on DFUs healing. Nonetheless, findings have so far not provided definitive answers. More studies are needed to clarify the role of zinc and its supplementation in this setting.

Magnesium and Diabetic Foot Ulcers: A Mini Review.

There is accumulating evidence that magnesium, an important mineral having a pivotal role in many physiological functions, may be important in development and healing of diabetic foot ulcers (DFUs). In this non-systematic mini review, we discuss the role of magnesium in DFUs, as well as the effects of magnesium administration in DFUs. Reduced Mg levels appear to be associated with DFUs. Moreover, Mg administration may be beneficial for the outcome of DFUs. Further investigation is imperative in order to shed more light on these findings.

Frailty, sarcopenia and diabetic kidney disease: where do we stand?

The aim of this narrative non-systematic review was to investigate the potential interplay among frailty syndrome, sarcopenia and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients. Data derived from a limited number of studies underline that DKD is a significant risk factor for frailty. On the other hand, frailty syndrome poses a higher risk for end-stage renal disease (ESRD) in subjects with DKD. In addition, frailty seems to affect the cognitive function and social life of DKD individuals, whilst as DKD deteriorates, there is a higher prevalence of sarcopenia which is a fundamental frailty factor. As a result, it is shown that a bidirectional relation is established between these entities, as diabetes mellitus (DM) affects the components of frailty and sarcopenia and vice versa. This vicious cycle is created through multiple pathophysiologic mechanisms, including the anabolic role of insulin, low-grade inflammation, cytokines and endothelial function, prompting further investigation in this area. Specific nutritional and exercise interventions are imperative to be established in order to ameliorate potential adverse outcomes, concerning these entities.

Significance of Circulating Cell-Free DNA Biomarkers in HBeAg-Negative Chronic Hepatitis B Virus Infection and Their Changes after Treatment Initiation.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a common chronic liver disease that is closely associated with increased morbidity and mortality. Circulating cell-free DNA (cf-DNA) and global DNA methylation, expressed as circulating levels of 5-methyl-2'-deoxycytidine, are increasingly used to monitor chronic inflammatory diseases of several etiologies. This study attempts to investigate the serum levels of circulating cf-DNA and 5-methyl-2'-deoxycytidine in HBeAg-negative patients with chronic infection (carriers) and chronic hepatitis B (CHB), as well as their changes after treatment initiation in CHB. METHODS: Serum samples from a total of 61 HBeAg-negative patients (30 carriers and 31 CHB patients) were included in order to quantify the levels of circulating cf-DNA and 5-methyl-2'-deoxycytidine. In addition, serum samples from 17 CHB patients in complete virological and biochemical remission after initiation of treatment with a nucleos(t)ide analogue were included. RESULTS: Circulating cf-DNA concentration was significantly increased after the initiation of treatment (15 vs. 10 ng/mL, p = 0.022). There was a trend in higher mean levels of circulating 5-methyl-2'-deoxycytidine in carriers compared to CHB patients (211.02 vs. 175.66 ng/mL, p = 0.089), as well as a trend in increasing 5-methyl-2'-deoxycytidine levels after treatment initiation in CHB patients compared to pre-treatment levels (215 vs. 173 ng/mL, p = 0.079). CONCLUSIONS: Both circulating levels of cf-DNA and 5-methyl-2'-deoxycytidine might be useful biomarkers in order to monitor liver disease activity and response to antiviral treatment in HBeAg-negative chronic HBV patients, but further studies are essential in order to validate these intriguing findings.

Bronchial Asthma and Sarcopenia: An Upcoming Potential Interaction.

BACKGROUND: Sarcopenia seems to be an emerging health issue worldwide, concerning the progressive loss of skeletal muscle mass, accompanied by adverse outcomes. Asthma is a chronic inflammatory respiratory condition that is widespread in the world, affecting approximately 8% of adults. Although data are scarce, we aim to shed light on the potential association between low muscle mass and asthma and point out any probable negative feedback on each other. METHODS: We searched within the PubMed, Scopus, MEDLINE, and Google Scholar databases. STUDY SELECTIONS: Three studies were included in our analysis. Only original studies written in English were included, while the references of the research articles were thoroughly examined for more relevant studies. Moreover, animal model studies were excluded. RESULTS: 2% to 17% of asthmatics had sarcopenia according to the existent literature. Sarcopenic asthmatic patients seem to have reduced lung function, while their mortality risk may be increased. Furthermore, patients with asthma- chronic obstructive pulmonary disease (COPD) overlap syndrome phenotype and sarcopenia might have a higher risk of osteopenia and osteoporosis progression, leading consequently to an increased risk of fractures and disability. CONCLUSIONS: Emerging data support that pulmonologists should be aware of the sarcopenia concept and be prepared to evaluate the existence of low muscle mass in their asthmatic patients.

B12 levels and frailty syndrome.

Vitamin B12, widely known as cobalamin, is a water-soluble vitamin crucial for human metabolism. It is synthesized only by prokaryotic organisms and since humans do not have the ability to synthesize it, they rely on its exogenous dietary intake. After its consumption, vitamin B12 undergoes a complicated procedure of absorption and assimilation and it is essential for cellular function, especially for nervous system, red blood cell production and DNA synthesis. Deficiency of vitamin B12 is considered as an important public health issue worldwide, while it is common in the elderly. Deficiency of this vitamin, as well as high levels, indicate a risk factor for morbidity with various clinical manifestations. Frailty is an age-related syndrome, which affects the elderly and is characterized by decreased function in many physiological systems, accompanied by vulnerability to stressors. A narrative non-systematic mini review of the literature was conducted and highlighted that vitamin B12 levels may have an impact on frailty and vice versa. As shown in several studies, vitamin B12 levels may be related to sarcopenia, cognitive and musculoskeletal disorders, neurological or psychiatric symptoms, which are closely linked to frailty. Furthermore, it is suggested that the extensions of frailty may affect the bioavailability of vitamin B12.

Vitamin B12 and Diabetic Foot: Α Mini-Review.

This narrative mini-review article aimed to investigate the potential association of vitamin B12 levels with diabetic neuropathy (DN) and diabetic foot ulcers (DFUs). It was demonstrated that B12 deficiency seems to be related to DFUs in cases of metformin administration and bariatric surgery. B12 supplementation with dietary measures and agents may improve DN and quality of life (QoL). However, data are still preliminary and more experience is needed.

Sarcopenia, Frailty and Diabetic Foot: A Mini Narrative Review.

The aim of this narrative mini review was to investigate the potential association of the diabetic foot (DF) with sarcopenia and frailty. Data is still limited, but it appears that DF patients may be more prone to frailty. In addition, patients with DF and sarcopenia exhibit more frequently foot ulcers and amputations, as well as increased mortality rates post-operatively. Further studies are now needed to see how these realizations may be used in clinical practice, aiming to improve DF outcomes.

Frailty in metabolic syndrome, focusing on nonalcoholic fatty liver disease.

In recent years, frailty has been increasingly recognized among researchers of distinct medical specialties worldwide. Frailty comprises a complex of multisystemic physiological decline, reduced physiologic reserve, and vulnerability to stressors. Frail people tend to have a shorter lifespan and greater disability, morbidity and mortality. In the field of hepatology, frailty is identified in nearly 50% of patients who have cirrhosis of any cause. The most predominant cause of chronic liver disease is nonalcoholic fatty liver disease (NAFLD), considered as the hepatic manifestation of the metabolic syndrome (MetS). Although it is viewed as a benign disease, it may progress to nonalcoholic steatohepatitis (NASH), characterized by the additional emergence of inflammation and hepatocyte ballooning, with or without fibrosis. During the progression of NAFLD to NASH and liver cirrhosis, NAFLD patients present sarcopenia along with lower skeletal muscle strength and function. Moreover, aging and the increased prevalence of comorbidities further exacerbate their physical performance. The aforementioned features are strongly associated with the frailty phenotype, implying that the latter could be associated with both MetS and NAFLD. Although it is a relatively new topic of research interest, in this review we aim to provide a synopsis of the current literature dealing with the interplay between frailty and MetS, and to shed more light on the association between NAFLD and frailty. Finally, we discuss the potential pathophysiological mechanisms linking the distinct features of MetS and NAFLD with aspects of the frailty phenotype.