Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome.

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the "Victor Babes" Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 µmol/L vs. 84.5 µmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (ß = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 µmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.

Clinical Outcomes and Molecular Predictors of Pembrolizumab (Keytruda) as a PD-1 Immune Checkpoint Inhibitor in Advanced and Metastatic Cervical Cancer: A Systematic Review and Meta-Analysis.

This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We adhered to the PRISMA guidelines for systematic reviews, conducting a database search in PubMed, Scopus, and Embase. The eligibility criteria centered on clinical outcomes, including the overall survival (OS), progression-free survival (PFS), and immune-related biomarkers post-pembrolizumab therapy. We included both prospective and retrospective studies that detailed clinical outcomes and molecular characteristics predictive of therapeutic response. Our search yielded six studies involving 846 patients treated with pembrolizumab from 2017 to 2022. The meta-analysis of these studies showed that pembrolizumab, used as monotherapy or in combination with chemotherapy, extended the OS by a weighted median of 10.35 months and the PFS by 8.50 months. The treatment demonstrated a pooled objective response rate (ORR) of 22.39%, although the I2 test result of 67.49% showed a high heterogeneity among the studies. Notably, patients with high PD-L1 expression (CPS ≥ 10) experienced improved outcomes in terms of the PFS and OS. The most common complications were fatigue, diarrhea, and immune-related adverse events. Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains a good safety profile, reinforcing its treatment potential for patients with advanced and metastatic cervical cancer. Future studies should explore long-term effects and strategies to integrate pembrolizumab optimally into current treatment regimens, aiming to maximize patient benefits and effectively manage side effects.

Aflibercept Versus Bevacizumab as First-Line Therapy in Age-Related Macular Degeneration.

BACKGROUND: AMD (age-related macular degeneration) is the main cause of central vision loss in the population over 60 years old. AMD does not affect peripheral vision and complete blindness does not occur, instead, central vision is affected both for distance and for near. The purpose of this study is to evaluate the neovascular form of AMD treatment and compare ocular and systemic effects after intravitreal injection of aflibercept, respectively after bevacizumab when administered in comparable dosages and regimens. We conducted a retrospective, single-center study from June 2021 to December 2022 and enrolled 20 patients with neovascular AMD who had not received any prior treatment for this condition. We randomly assigned them to two groups of 10: group one received aflibercept and group two received bevacizumab as intravitreal injections under aseptic conditions. We excluded 2 patients who did not meet the criteria and ended up with two groups of 9 patients who received monocular treatment. We gave the patients 3 monthly injections of anti-VEGF agent and followed them up at 1 month, 3 months, and 9 months after the treatment. We assessed their visual acuity, intraocular pressure and OCT appearance at each follow-up visit. The primary outcome was visual acuity. All 18 patients included in the study reported an improvement in visual acuity after the intervention. When comparing the two anti-VEGF agents, data revealed the effect of aflibercept was prompter and more long-lasting. Areas of retinal ischemia appeared in both cases. However, they were observed faster in the case of patients treated with aflibercept. Thus, neovascular AMD is a disease that occurs with age, it can be early detected by OCT and slowed the progression to central blindness with intravitreal treatment.

A rare encounter with two cases of Budd­Chiari syndrome in the Emergency Department: A case report.

Budd-Chiari syndrome (BCS) is a rare disorder clinically characterized by abdominal pain, hepatomegaly and ascites. The condition is often related to thrombosis of the hepatic veins or the terminal portion of the inferior vena cava. A myeloproliferative disorder is the most identified underlying prothrombotic risk factor, although almost one-half of affected patients are now recognized as having multiple underlying prothrombotic risk factors. Doppler ultrasound may be enough to confirm the diagnosis of BCS; however, computed tomography or magnetic resonance imaging is often employed. Anticoagulant therapy is the cornerstone of BCS treatment, but most patients also need additional treatment strategies. Most patients with BCS are now treated by endovascular intervention, which has improved survival rate in those afflicted by this disease. The long-term course of the disease can be complicated by progression or recurrence of the underlying myeloproliferative disorder. The present study reports the cases of two patients with BCS with the aim of alerting healthcare workers in Emergency Departments of this less common diagnosis in patients presenting with frequent complaints of abdominal pain.

The role of Anti-VEGF agents in treatment of neovascular glaucoma.

Aim: The aim of this study was to show the efficacy of intravitreal treatment with Bevacizumab (Avastin) in patients with secondary neovascular glaucoma, in different stages of the disease. Method: A retrospective study was performed on 67 patients with neovascular glaucoma. The main parameters evaluated were the patients' history, slit lamp examination, visual acuity, ocular tonometry, fundus examination, gonioscopy, and visual field. Results: It was observed that the pathology had a preponderance in males of the 6th decade, with frequently unilateral damage. Patients were referred to an ophthalmologist when the diseases reached an advanced stage, usually when the visual acuity had no light perception and the intraocular pressure was over 45 mmHg. However, the treatment with Avastin intravitreal showed a good evolution, with regression of neovessels in the first 4-7 days and maintenance of intraocular pressure within normal limits in about 60% of cases, 3 months after injection. Conclusion: The most effective treatment in secondary neovascular glaucoma is the correct therapy of the main disease. The association of Avastin and laser photocoagulation leads to regression in iris and retinal neovessels. Abbreviations: anti-VEGF = anti-Vascular Endothelial Growth Factor, PDGF = Platelet Derived Growth Factor, bFGF = basic Fibroblast Growth Factor.

Relationship between allergic rhinitis and allergic conjunctivitis (allergic rhinoconjunctivitis) - review.

Allergic rhinitis and allergic conjunctivitis are so frequently associated that the need to coin a new name to describe the simultaneous manifestations generated the term allergic rhinoconjunctivitis. The significant impact of rhinoconjunctivitis on the quality of life and the wellbeing of the patients is the reason why the medical community shows a great interest to this disease. Another aspect is the financial burden that is not negligible. The anatomical connection between the organs involved facilitates the propagation of the disease. The allergic pathophysiological mechanisms implicated in allergic rhinitis and conjunctivitis also share common features. The diagnosis of rhinoconjunctivitis is based on the concordance between the symptoms, the clinical examination, and the diagnostic tests that should reveal the existence of an allergen specific IgE in vivo or in vitro. Whilst the nasal smear for eosinophils is considered a reliable diagnostic test for allergic rhinitis, the occurrence of eosinophils in the conjunctive is not a trustworthy indicator of allergy. The therapy of allergic rhinoconjunctivitis is based on patient education, pharmacotherapy, and allergen-specific immunotherapy. The local treatment for the allergic rhinitis is primarily based on topical corticosteroids that also manage the ocular symptoms. The first line of treatment of the ocular manifestations is represented by topical antihistamines and mast-cell stabilizers or double action drugs.

Potential role for pentoxifylline as an anti-inflammatory drug for patients with acute coronary syndrome.

The link between inflammation and acute coronary syndrome (ACS) remains to be sufficiently elucidated. It has been previously suggested that there is an inflammatory process associated with ACS. Pentoxifylline, a methylxanthine derivate, is known to delay the progression of atherosclerosis and reduce the risk of vascular events, especially by modulating the systemic inflammatory response. The present study is a single-blind, randomized, prospective study of pentoxifylline 400 mg three times a day (TID) added to standard therapy vs. standard therapy plus placebo in ACS patients with non-ST elevation myocardial infarction (NSTEMI). Patients with ACS were randomized to receive standard therapy plus placebo in one arm (group A; aspirin, clopidogrel or ticagrelor, statin) and in the other arm (group B) pentoxifylline 400 mg TID was added to standard therapy. The primary outcome was the rate of major adverse cardiovascular events (MACEs) at 1 year. A total of 500 patients underwent randomization (with 250 assigned to group A and 250 to group B) and were followed-up for a median of 20 months. The mean age of the patients was 62.3±10.3 years, 80.4% were male, 20.8% had diabetes, 49.4% had hypertension, and 42% were currently smoking. The statistical analysis was performed for 209 patients in group A and 210 patients in group B (after dropouts due to study drug discontinuation). A primary endpoint occurred in 12.38% (n=26) of patients in group B, as compared with 15.78% (n=33) of those in group A [relative risk (RR), 0.78; 95% confidence interval (CI), 0.486-0.1.263; P=0.40], including cardiovascular death (RR, 0.93; 95% CI, 0.48-1.80, P=0.84), non-fatal myocardial infarction (RR, 1.1; 95% CI, 0.39-3.39, P=0.78), stroke (RR, 0.99; 95% CI, 0.14-6.99, P=0.99) and coronary revascularization (RR, 0.12; 95% CI, 0.015-0.985, P=0.048). Thus, adding pentoxifylline to standard treatment in patients with ACS did not improve MACE at 1 year but had some benefit on the need for coronary revascularization.

A survey to assess the incidence of Down syndrome risk in rural southwestern Romania.

Despite the significant evolution in recent years in the medical field, many fetal conditions that can be detected in the early stages, remain a social and economic burden due to a lack of diagnostic and treatment programs. The main objective of the present study was to realize a screening program related to the early detection of Down syndrome, by analyzing biochemical and imaging markers, in women from the rural areas of Southwest Romania. Accordingly, data from 269 pregnant women were taken into evaluation for maternal age, maternal weight, smoking and diabetic statuses, along with ultrasound measurements that were performed to establish fetal nuchal translucency (FNT) and biochemical analysis of free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein (PAPP-A). Patients at high risk for trisomy 21 (≥1:250) were counseled and the optimal protocol was established for each case. Of the 269 patients studied, 5.6% were included in the risk group based on ß-hCG-associated MoM (multiple median approaches) analysis, sonographic measurements and maternal age correlation. Specifically, 60% of patients at risk presented a ß-hCG MoM value >1.5 and 20% of patients at risk presented a value ≤0.5 for PAPP-A MoM, and the average maternal age was 33. Measurement of FNT and serum markers, together with associated MoM intervals, was not sufficient to establish the diagnosis of trisomy 21 and to make a risk group inclusion. In summary, the association between sonographic measurements and serum marker values, together with maternal age, are predetermined and indispensable conditions for the most accurate classification in a high-risk group.

Assessment of Betulinic Acid Cytotoxicity and Mitochondrial Metabolism Impairment in a Human Melanoma Cell Line.

Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 µM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.

Bevacizumab in Wet AMD treatment: A tribute to the thirteen years of experience from the beginning of the anti-VEGF era in Romania.

This study aimed to identify and describe anatomical and functional changes on short (1-3 months) and medium (6-12 months) term after intravitreal injections of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) in the context of exudative form of age-related macular degeneration (AMD). We performed a retrospective, analytical, interventional study, based on a series of cases with exudative form of AMD, which also comprised a prospective component related to the inclusion and treatment of the patients with a very new interventional method for that time (2006) and the follow-up of the effects of intravitreal injection of bevacizumab (1.25 mg) therapy in three monthly doses for short (1-3 months) and medium (6-18 months) periods of time. The follow-up of these patients was made by determining visual acuity (VA) as best corrected visual acuity (BCVA) at baseline and at every visit, slit lamp examination with contact or noncontact lenses each time, and optical coherence tomography and/or angiofluorography, applied only for certain patients, at various times of the study. In total, 376 intravitreal injections were administered to 117 eyes of 96 patients. The VA improved in the assessment of 3 months in 77 eyes (66%), either subjective (by the patient) or objectively quantified (by the physician). In 40 eyes (34%), there was no change in VA. In patients for whom optical coherence tomography could be performed, a significant reduction of the macula's thickness was found. The use of bevacizumab in subretinal neovascular membrane treatment is effective and safe on short and medium term, with the improvement of BCVA and reduction of macular edema in a significant number of cases.