The Effect of α-lipoic Acid on C-Reactive Protein Level: A Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Studies.

The C-reactive protein is generally considered a marker of inflammation, and it is widely used in clinical practice as a minimally invasive index of any ongoing inflammatory response. Alpha-lipoic acid (ALA) supplementation can be beneficial for human health, especially in the sense of its anti-inflammatory action. The aim of this meta-analysis was to, based on the currently available highest level of evidence (prospective, randomized, double-blind, and placebo-controlled data), investigate the effect of ALA supplementation on CRP levels. Prospective, randomized, double-blind, and placebo-controlled clinical trials were extracted after a systematic search of PubMed, the Cochrane Library, the Web of Science, EMBASE, and the Scopus databases. A random effect model was used in this meta-analysis to investigate the influence of ALA on the blood CRP level. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. This meta-analysis provided evidence of the positive effect of ALA on the reduction of the blood CRP level. The subgroup analysis and meta-regression results indicated that ALA can reduce the CRP level when administrated at a 600 mg dose, and not in higher or lower doses. Also, a shorter duration of study positively correlates with the reduction of CRP after ALA supplementation.

Occluded Superior Mesenteric Artery and Vein. Therapy with the Stable Gastric Pentadecapeptide BPC 157.

BACKGROUND: We investigated the occluded essential vessel tributaries, both arterial and venous, occluded superior mesenteric vein and artery in rats, consequent noxious syndrome, peripherally and centrally. As therapy, we hypothesized the rapidly activated alternative bypassing pathways, arterial and venous, and the stable gastric pentadecapeptide BPC 157 since it rapidly alleviated venous occlusion syndromes. METHODS: Assessments were performed for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress), including portal hypertension, caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, the multiple organs lesions, heart, lung, liver, kidney and gastrointestinal tract, including brain (swelling, and cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus lesions). Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 min ligation-time. RESULTS: BPC 157 rapidly activated collateral pathways. These collateral loops were the superior mesenteric vein-inferior anterior pancreaticoduodenal vein-superior anterior pancreaticoduodenal vein-pyloric vein-portal vein pathway, an alternative pathway toward inferior caval vein via the united middle colic vein and inferior mesenteric vein through the left colic vein, and the inferior anterior pancreaticoduodenal artery and inferior mesenteric artery. Consequently, BPC 157 counteracted the superior sagittal sinus, portal and caval hypertension, aortal hypotension, progressing venous and arterial thrombosis peripherally and centrally, ECG disturbances attenuated. Markedly, the multiple organs lesions, heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain lesions, and oxidative stress in tissues were attenuated. CONCLUSIONS: BPC 157 therapy rapidly recovered rats, which have complete occlusion of the superior mesenteric vein and artery.

Complex Syndrome of the Complete Occlusion of the End of the Superior Mesenteric Vein, Opposed with the Stable Gastric Pentadecapeptide BPC 157 in Rats.

Background. Gastric pentadecapeptide BPC 157 therapy in rats compensated irremovable occlusion of various vessels and counteracted the consequent multiorgan dysfunction syndromes by activation of the corresponding collateral bypassing loops. Thus, we used BPC 157 therapy against the irremovable occlusion of the end of the superior mesenteric vein. Methods. Assessments, for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress) include the portal and caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension, systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, and heart, lung, liver, kidney and gastrointestinal tract, in particular, and brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus) lesions. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 or 15 min ligation time. Results. BPC 157 rapidly activated the superior mesenteric vein-inferior anterior pancreati-coduodenal vein-superior anterior pancreaticoduodenal vein-pyloric vein-portal vein pathway, reestablished superior mesenteric vein and portal vein connection and reestablished blood flow. Simultaneously, toward inferior caval vein, an additional pathway appears via the inferior mesenteric vein united with the middle colic vein, throughout its left colic branch to ascertain alternative bypassing blood flow. Consequently, BPC 157 acts peripherally and centrally, and counteracted the intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, ECG disturbances attenuated, abolished progressing venous and arterial thrombosis. Additionally, BPC 157 counteracted multiorgan dysfunction syndrome, heart, lung, liver, kidney and gastrointestinal tract, and brain lesions, and oxidative stress in tissues. Conclusion. BPC 157 therapy may be specific management also for the superior mesenteric vein injuries.

Occlusion of the Superior Mesenteric Artery in Rats Reversed by Collateral Pathways Activation: Gastric Pentadecapeptide BPC 157 Therapy Counteracts Multiple Organ Dysfunction Syndrome; Intracranial, Portal, and Caval Hypertension; and Aortal Hypotension.

Gastric pentadecapeptide BPC 157 therapy counteracts multiple organ dysfunction syndrome in rats, which have permanent occlusion of the superior mesenteric artery close to the abdominal aorta. Previously, when confronted with major vessel occlusion, its effect would rapidly activate collateral vessel pathways and resolve major venous occlusion syndromes (Pringle maneuver ischemia, reperfusion, Budd-Chiari syndrome) in rats. This would overwhelm superior mesenteric artery permanent occlusion, and result in local, peripheral, and central disturbances. Methods: Assessments, for 30 min (gross recording, angiography, ECG, pressure, microscopy, biochemistry, and oxidative stress), included the portal hypertension, caval hypertension, and aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis; ECG disturbances; MDA-tissue increase; and multiple organ lesions and disturbances, including the heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus). BPC 157 therapy (/kg, abdominal bath) (10 µg, 10 ng) was given for a 1-min ligation time. Results: BPC 157 rapidly recruits collateral vessels (inferior anterior pancreaticoduodenal artery and inferior mesenteric artery) that circumvent occlusion and ascertains blood flow distant from the occlusion in the superior mesenteric artery. Portal and caval hypertension, aortal hypotension, and, centrally, superior sagittal sinus hypertension were attenuated or eliminated, and ECG disturbances markedly mitigated. BPC 157 therapy almost annihilated venous and arterial thrombosis. Multiple organ lesions and disturbances (i.e., heart, lung, liver, and gastrointestinal tract, in particular, as well as brain) were largely attenuated. Conclusions: Rats with superior mesenteric artery occlusion may additionally undergo BPC 157 therapy as full counteraction of vascular occlusion-induced multiple organ dysfunction syndrome.

Efficacy and Safety of Armolipid Plus®: An Updated PRISMA Compliant Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

Armolipid Plus® is a multi-constituent nutraceutical that claims to improve lipid profiles. The aim of this PRISMA compliant systematic review and meta-analysis was to globally evaluate the efficacy and safety of Armolipid Plus® on the basis of the available randomized, blinded, controlled clinical trials (RCTs). A systematic literature search in several databases was conducted in order to identify RCTs assessing the efficacy and safety of dietary supplementation with Armolipid Plus®. Two review authors independently identified 12 eligible studies (1050 included subjects overall) and extracted data on study characteristics, methods, and outcomes. Meta-analysis of the data suggested that dietary supplementation with Armolipid Plus® exerted a significant effect on body mass index (mean difference (MD) = -0.25 kg/m2, p = 0.008) and serum levels of total cholesterol (MD = -25.07 mg/dL, p < 0.001), triglycerides (MD = -11.47 mg/dL, p < 0.001), high-density lipoprotein cholesterol (MD = 1.84 mg/dL, p < 0.001), low-density lipoprotein cholesterol (MD = -26.67 mg/dL, p < 0.001), high sensitivity C reactive protein (hs-CRP, MD = -0.61 mg/L, p = 0.022), and fasting glucose (MD = -3.52 mg/dL, p < 0.001). Armolipid Plus® was well tolerated. This meta-analysis demonstrates that dietary supplementation with Armolipid Plus® is associated with clinically meaningful improvements in serum lipids, glucose, and hs-CRP. These changes are consistent with improved cardiometabolic health.

Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies.

Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA and 2294 assigned to placebo. A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all p > 0.05). ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, neurological disorders, rheumatic affections, severe renal impairment, and status of children/adolescents at baseline.

Treatment of Hypertension Induced Albuminuria.

Regardless of having a similar antihypertensive effect, different antihypertensive drug classes have a different effect on albuminuria. Patients with albuminuria will usually need more than one drug to achieve blood pressure control, particularly if the aim is also to reduce albuminuria. Albuminuria is independently associated with cardiovascular and renal risk regardless of diabetes status. The recent ESC/ESH guidelines listed microalbuminuria among the hypertension-mediated organ damages. Albumin-to-creatinine ratio was suggested to be included in routine workup for evaluation of every hypertensive patient and changes in albuminuria were considered to have moderate prognostic value. Because of its specific effects on renal hemodynamic and glomerular structure, the ACEIs and ARBs should be prescribed in maximum tolerated doses. The MRAs can be considered in uncontrolled hypertensive patients. The CCBs can be used in addition to the RAAS blockade. Data on antialbuminuric effect of the new CCBs generation (T-type and N-type calcium channel blockers) is promising and they might be preferential CCBs when available. In case of resistant hypertension, thiazide or thiazide-like diuretic has to be added into the combination with RAAS blockers and other antihypertensive drugs. Low-salt intake has to be recommended for all hypertensive patients, particularly those with albuminuria. A multifactorial and early antialbuminuric approach should be started even when albuminuria values are below the cut-off value for microalbuminuria.

Morphological and Angiographic Peripheral Retinal Changes in Patients with Age-Related Macular Degeneration.

OBJECTIVE: To show morphologic and angiographic changes in the peripheral retina in patients with age-related macular degeneration (AMD) using wide-field fundus imaging, and to compare these findings with those from healthy controls. DESIGN: Cross-sectional clinical study. PARTICIPANTS: In total, 152 patients with clinical AMD and 150 healthy controls (without AMD in either macula) were studied. Subjects were ≥50 years of age. Exclusion criteria were diabetic retinopathy, previous retinal surgery, high myopia, or dense cataract, as well as any retinal inflammatory, degenerative, or occlusive disease. METHODS: For both groups of patients, color fundus images were captured with the Optos P200 MA camera (Optos, Dunfermline, Scotland). Image analysis software was used to characterize each image. Angiography was performed on the AMD group only. Morphological and angiographic peripheral retinal changes were studied per the frequency of their occurrence, the affected peripheral retina (clock hours), and the localization of peripheral changes with regard to the eye equator. Statistical significance was defined at a level of P < 0.05. MAIN OUTCOME MEASURES: Peripheral changes in both groups according to their type and frequency (percentage of eyes with detected retinal changes), the number of clock hours of affected peripheral retina, and their localization with regard to the equator of the eye. RESULTS: Drusen, reticular pigmentary changes, and paving stone degeneration occurred more frequently in the AMD group than in controls (P < 0.001, P < 0.001, and P < 0.001 respectively), whereas white without pressure occurred more frequently in the control group (P = 0.027). In both groups, peripheral retinal changes were observed peripheral to the equator in more than 40% of analyzed eyes. In control Croatian subjects, peripheral drusen were seen in 38% of subjects compared with 68% of AMD subjects. CONCLUSION: Drusen, reticular pigmentary change , and paving stone degeneration occur significantly more frequently in subjects with AMD compared with controls. White without pressure degeneration was present in a high percentage of control subjects.

Muscular Adverse Drug Reactions Associated with Proton Pump Inhibitors: A Disproportionality Analysis Using the Italian National Network of Pharmacovigilance Database.

INTRODUCTION: Proton pump inhibitors (PPIs) have been implicated in the occurrence of moderate to severe myopathies in several case reports. AIM: This study was performed to assess the reporting risk of muscular adverse drug reactions (ADRs) associated with PPIs in the Italian National Network of Pharmacovigilance database. METHODS: A disproportionality analysis (case/non-case) was performed using spontaneous reports collected in the database between July 1983 and May 2016. Reporting odds ratio (ROR) and 95% confidence intervals (CIs) were calculated as a measure of disproportionality. In a secondary and tertiary analysis, we explored the association of PPIs with muscular ADRs after taking into account the masking effect of statins. Moreover, the possibility of an interaction between PPIs and statins, leading to the occurrence of muscular ADRs, was also tested. RESULTS: The study was carried out on 274,108 reports. The ROR of muscular ADRs for PPIs, adjusted for age and gender, was 1.484 (95% CI 1.204-1.829; p < 0.001), whereas the ROR for rhabdomyolysis was 0.621 (95% CI 0.258-1.499). Similar results were obtained in the secondary analysis. The tertiary analysis, where PPIs were considered regardless of whether their role was suspected or concomitant, showed a potential disproportionate reporting for the combination PPIs-rhabdomyolysis (ROR 1.667, 95% CI 1.173-2.369; p < 0.01). The PPIs-statins combination was not associated with an enhanced ROR of muscular ADRs/rhabdomyolysis compared with statins alone. CONCLUSIONS: This explorative study suggests that the class of PPIs could be involved in reports of muscular ADRs, rather than any other ADR, more frequently than any non-statin drug. Our results must be corroborated by further studies.

Melanomas in Renal Transplant Recipients: A Single-center Study.

Skin cancers are the most common malignancies in renal transplant recipients, with squamous-cell and basal-cell cancers accounting for the majority of all skin cancer cases. Melanoma is relatively rare in this group of patients. From 1973 to May 2017, out of 1889 patients who received allografts at our institution, 4 developed melanoma. After the mean follow-up of 11.5 months, 2 patients died and 2 are still alive with functioning allografts. Malignancies were localized in the legs in both female patients, and in the neck and head in 1 male patient each. Compared to the general population of Croatia, renal transplant recipients from our cohort have 6.85 times higher risk for development of melanoma. Regular screenings and patient education are mandatory, especially in Mediterranean countries.

Integrated information for integrated care in the general practice setting in Italy: using social network analysis to go beyond the diagnosis of frailty in the elderly.

BACKGROUND: Frailty has been defined in different ways and several diagnostic tools exist, but most of them are not applicable in routine primary care. Nonetheless, general practitioners (GPs) have a natural advantage in identifying frailty, due to their continued access to patients, patient-centered approach and training. GPs have also an advantage in conducting population-based evaluation as consequence of their role of gatekeepers of the health care system. This paper aims to identify those socio-demographic and clinical profiles and the relative information sources that, from the GPs' perspective, act as frailty markers, not solely as a diagnosis of state but as the ability to identify a patient's trajectory, over time, through the aging process. METHODS: This study was performed as a survey within a population aged 75 and over, attending 148 GPs in Italy. A total of 23,996 patients were classified by GPs in distinct frailty status, without the use of a specific evaluation tool, but only referring to general indications. Co-morbidity was objectively assessed by a record-linkage with previous hospitalizations, in order to assess the occurrence of previous illnesses that could be associated with the likelihood of being identified as frails or at risk. The methodological approach is based on social network analysis (SNA), suited to explore relational aspects of complex phenomena. RESULTS: Our findings reveal that GPs are able to perform low cost population-based evaluation, by exploiting the advantages of their approach to patients, combined with the information derived from their daily practice and from other sources currently available. CONCLUSION: We believe that informative integration among different sources of available data can provide a comprehensive picture of the health state of patients in a shorter time and at lower cost. The identification of limited patient trajectories based on these observations can enable the development of critical biomarkers/diagnostics and prognostic indicators that will enhance patient care and potentially reduce inappropriate healthcare use. We also believe that network analysis is an extremely flexible research tool and a rich theoretical paradigm, and it may be used in the healthcare planning.

Prevalence of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in Population of North-West Croatia Aged 40 and Over

The purpose of this study was to assess the prevalence of pseudoexfoliation syndrome and pseudoexfoliation glaucoma and to evaluate its association with open-angle glaucoma in patients attending the Department of Ophthalmology, Dr Tomislav Bardek General Hospital in Koprivnica, northwestern Croatia. This prospective study was conducted at Dr Tomislav Bardek General Hospital between December 2012 and October 2013. A total of 5349 subjects aged 40 or above presenting for general ophthalmic examination were screened for pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Each patient underwent complete ophthalmologic examination including ocular history, visual acuity testing, slit-lamp examination, applanation tonometry, optic disc evaluation, visual field analysis, and gonioscopy if glaucoma was suspected. Exclusion criteria were pseudophakic and/or aphakic patients of any age, patients with concomitant congenital eye disease, and patients with very dense ocular media opacities. Out of 5349 patients examined, there were 1994 (38.38%) males and 3201 (61.61%) females. The prevalence of pseudoexfoliation syndrome was 3.6% and primary open angle glaucoma 9.4%, out of which 23.6% with pseudoexfoliation glaucoma. The findings of this study improve our knowledge of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in Croatia, particularly in the northwest region.

Bilateral Pseudomonas aeruginosa endogenous endophthalmitis in an immune-competent patient with nosocomial urosepsis following abdominal surgery.

Endogenous endophthalmitis is a vision-threatening condition that results from hematogenous spread of infection to the eye, originating from a distant primary focus. It is considered as a rare entity that predominantly occurs in immune-compromised patients. We present a case of a critically ill immune-competent patient who underwent abdominal surgery later followed by nosocomial urosepsis complicated with bilateral Pseudomonas aeruginosa endogenous endophthalmitis that resulted in blindness. This case is clinically important because of the absence of predisposing factors for this kind of eye infection.

Intralesional triamcinolone acetonide injection for chalazion.

The aim of the study was to evaluate the efficacy of intralesional triamcinolone acetonide injection in primary and recurrent chalazion. The study included 30 patients with primary and recurrent chalazion (37 cases) and 24 patients as a control group. Patients with primary and recurrent chalazion received intralesional injection of 0.1 to 0.2 mL triamcinolone acetonide (40 mg/mL). Control group received intralesional injection of 0.1 to 0.2 mL 0.9% NaCl. Data on the lesion size, including digital color photography, lesion regression or recurrence, and complete ophthalmic examination were recorded at the time of injection and after a week or two until resolution or surgical excision. Success was defined as at least 80% decrease in size with no recurrence. Resolution of the lesion was found in 35 cases after one or two injections, with a mean time to resolution of 15.27 +/- 6.12 days. Subcutaneous injection of the steroid triamcinolone acetonide in primary and recurrent chalazion appears to be a simple and efficacious therapeutic option for chalazion.

Common variant in myocilin gene is associated with high myopia in isolated population of Korcula Island, Croatia.

AIM: To study the association between genetic variants in myocilin and collagen type I alpha 1 genes and high myopia in an isolated island population. METHODS: A total of 944 examinees from the genetic epidemiology study conducted on the island of Korcula, Croatia, were included in the study. We selected 2 short nucleotide polymorphisms (SNP) available in our genome-wide scan set of SNPs that were previously associated with high myopia and used them to replicate previous claims of possible association. RESULTS: Nineteen cases of high myopia, defined as the refraction of

Botulinum toxin A injection for primary and recurrent chalazia.

BACKGROUND: To study the efficacy and safety of subcutaneous botulinum toxin A injections in the treatment of primary and recurrent chalazia. METHODS: Prospective, placebo-controlled consecutive case-series trial. Sixty three patients were divided into two groups: group 1 consisting of 32 patients previously diagnosed with and treated for primary or recurrent chalazia with 2-5 international units (IU) in 0.2-0.5 ml of preserved saline solution of botulinum toxin injection, and group 2 consisting of 31 patients receiving placebo. The main outcome measures were localization and duration of the disease, size of chalazion before and after treatment, clinical resolution of chalazion, time to resolution, and complications of treatment. RESULTS: There was a clinically and statistically significant between-group difference in the rate of therapeutic success and post-therapeutic chalazion regression, but not in the rate of complications. CONCLUSIONS: Botulinum toxin A injection is effective and safe treatment for primary and recurrent chalazia. Lesion regression that did not respond to the average of two injections would benefit more from surgical excision or systemic antibiotic therapy.

Iridogoniodysgenesis syndrome: a case report.

A rare case is presented of iridogoniodysgenesis syndrome, an autosomal dominant inheritance disorder that includes abnormalities in the differentiation of the anterior segment structures and increased values of intraocular pressure, which at long run increases the risk of glaucomatous optic neuropathy. The syndrome is diagnosed when ocular changes are accompanied by extraocular structure anomalies such as maxillary hypoplasia, micro- and anodontia, redundant periumbilical skin, inguinal hernia and hypospadias (males). A 44-year-old male patient presented for treatment of retinal detachment on his left eye. Cataract surgery and pars plana vitrectomy with endolaser were done. Due to his vision loss, high intraocular pressure values bilaterally and positive family history of glaucoma, he was rehospitalized for complete glaucomatous diagnostic evaluation. The rare iridogoniodysgenesis syndrome and associated juvenile glaucoma were verified in the patient by positive family history of glaucoma, slit lamp iris hypoplasia and mild pupillary deformities, gonioscopic results of open angle with iridotrabecular synechiae and neovascularizations at the iris root and ciliary body, fundus examination showing optic disk changes with a cup to disk ratio of 0.9 and 0.8 for the right and left eye, respectively, visual field dG2 program abnormalities such as absolute scotomata within 30 degrees on both eyes, and finally optical coherent tomography results of the cup to disk area ratio of 0.9 and 0.8 for the right and left eye, respectively, with average thickness of the retinal nerve fiber layer of 51 mm and 72 mm for the right and left eye, respectively. Disease control was achieved with medicamentous therapy; however, continuous follow up of the patient is a priority to prevent the potential glaucomatous damage.