SHL Medical (Switzerland)

Background. Hypertension is currently recognized as a major health problem in young and middle-aged adults and is associated with a substantial deterioration in prognosis, underscoring the importance of early diagnosis and timely risk factor control. Objective. To assess the clinical, laboratory, and instrumental characteristics of naive young and middle-aged patients with essential hypertension in real-world outpatient clinical practice. Methods: study included 73 patients with essential hypertension (median age, 41.0 [37.0; 48.0] years; women, 53.4 %) with stage I-III, grade 1-2 hypertension who had not previously received antihypertensive therapy. Clinical characteristics, office blood pressure (BP), ambulatory blood pressure monitoring (ABPM), echocardiography, and routine clinical and biochemical blood test parameters were evaluated. Results. Most patients had grade 1 hypertension and stage I hypertension (93.1 % in both cases). Obesity and overweight were identified in 46.4 % and 37.2 % of patients, respectively. Elevated total cholesterol (>4.9 mmol/L) was observed in 53.4 % of patients, and low-density lipoprotein cholesterol >3.0 mmol/L in 71.2 %. The predominant ABPM phenotypes were day-time systolic-diastolic hypertension (45.2 %) and day-time isolated systolic hypertension (27.4 %). An increased rate of morning BP surge (systolic and diastolic) was recorded in 91.7 and 97.3 % of patients, respectively. Left ventricular hypertrophy was detected in 6.8 % of patients. Increasing body mass index was associated with unfavorable changes in laboratory and echocardiographic parameters, as well as with higher mean daytime systolic BP. Conclusions. In young and middle-aged adults, hypertension is associated with a high prevalence of cardiometabolic risk factors, prognostically unfavorable 24-hour BP profile abnormalities, and progressive structural and functional cardiac changes with increasing body weight.

BackgroundReal-world first-line maintenance (1LM) treatment data are limited for advanced/metastatic non-small cell lung cancer (a/mNSCLC).Materials and MethodsIn this electronic health record-derived, deidentified database study, eligible patients (≥18 years; diagnosed with stage III/IV non-small cell lung cancer [June 1, 2017-September 30, 2021]) initiated pembrolizumab-based 1LM after 4-6 cycles of first-line (1L) platinum-based chemotherapy-pembrolizumab ± pemetrexed. Study outcomes were real-world time to next treatment or death (rwTTNTD), overall survival (rwOS), and predictors of outcomes.ResultsOf 1944 patients analyzed (median follow-up, 12.2 months), 51.9% received 1LM pembrolizumab-pemetrexed and 48.1% pembrolizumab monotherapy. Median rwTTNTD and rwOS were 9.2 (95% CI: 8.5-9.8) and 18.7 (95% CI: 17.7-20.3) months, respectively. In multivariable analyses, factors significantly associated with shorter rwTTNTD included 5%-<10% (hazard ratio [HR], 1.34; 95% CI: 1.17-1.54) or ≥10% (HR, 1.69; 95% CI: 1.42-2.01) weight loss during 1L versus 0% or <5% weight loss. Programmed death-ligand 1 (PD-L1) expression 1%–49% (HR, 0.81; 95% CI: 0.71-0.93) or ≥50% (HR, 0.55; 95% CI: 0.47-0.64) and female sex (HR, 0.85; 95% CI: 0.75-0.95) were significantly associated with longer rwTTNTD. These variables were also significantly associated with shorter (weight loss 5%-<10%: HR, 1.52; 95% CI: 1.30-1.77; ≥10% HR, 2.06; 95% CI: 1.71-2.48) and longer rwOS (PD-L1 expression: 1%-49% HR, 0.84; 95% CI: 0.72-0.98; ≥ 50% HR, 0.57; 95% CI: 0.48-0.68; female sex: HR, 0.81; 95% CI: 0.71-0.92).ConclusionsPredictors of real-world clinical outcomes included 1L treatment, weight loss, PD-L1 status, and sex. Poor outcomes persisted despite immunotherapy-based 1LM availability, revealing an unmet need in this population.

We report data on survival and complications for a longitudinal cohort of 709 transfusion-dependent β-thalassemia major patients (51.1% males) born between 1970 and 1997 and followed through 2020 at seven major centers in Italy. Overall survival probability at 30 years was 83.6% (95%CI: 78.5-89.1) in the oldest birth cohort (1970-1974) compared with 93.3% (95%CI: 88.6-98.3) in the youngest birth cohort (1985-1997) (p=0.073). Females showed better survival than males (p=0.022). There were a total of 93 deaths at a median age of 23.2 years with the most frequent disease-related causes being heart disease (n=53), bone marrow transplant (BMT) complication (n=10), infection (n=8), liver disease (n=4), cancer (n=3), thromboembolism (n=2) and severe anemia (n=1). There was a steady decline in the number of deaths due to heart disease from the year 2000 onwards and no death from BMT was observed after the year 2010. A progressive decrease in the median age of BMT was observed in younger birth cohorts (p < 0.001). A total of 480 (67.7%) patients developed ≥1 complication. Patients in younger birth cohorts demonstrated better complication-free survival (p < 0.001) which was comparable between sexes (p=0.230). Independent risk factors for death in multivariate analysis included heart disease (HR: 4.63, 95%CI: 1.78-12.1, p=0.002), serum ferritin >1000 ng/mL (HR: 15.5, 95%CI: 3.52-68.2, p < 0.001), male sex (HR: 2.75, 95%CI: 0.89-8.45, p=0.078), and splenectomy (HR: 6.97, 95%CI: 0.90-54.0, p < 0.063). Survival in patients with β-thalassemia major continues to improve with adequate access to care, best practice sharing, continued research, and collaboration between centers.

Aim. To identify and characterize the associations of the presence and severity of atherosclerosis of various localization with the blood level of biochemical parameters, as well as to assess the potential of their use as markers of metabolic disorders with increased atherogenic potential.Material and methods. The study included 216 patients (men, 53%) aged 24-87 years (mean age, 61,5±10,73 years). All patients underwent coronary angiography, carotid (CA) and femoral arterial (FA) duplex ultrasound to assess the presence and severity of atherosclerosis. In blood serum/plasma, biochemical parameters were analyzed using standard methods.Results. Based on the analysis of circulating biomarker profile, diagnostic complexes have been established that allow assessing atherosclerosis of different localization. According to the data obtained, the determinants of coronary and CA atherosclerosis are endothelial dysfunction (concentration of nitric oxide metabolites &lt;36,0 μmol/L) and an increased level of creatinine (≥73,0 μmol/L). The specific markers associated with severe atherosclerosis of coronary and FAs (but not CA) were low high-density lipoprotein cholesterol (≤1,0/1,2 μmol/L for male/ female, respectively) and an increased C-reactive protein level (≥1,0 mg/l). Severe peripheral atherosclerosis (CA and FA involvement) was associated with hyperglycemia (glucose ≥6,1 μmol/L), while severe FA atherosclerosis — with hyperinsulinemia (insulin ≥14,0 μU/ml).Conclusion. The analysis of associations of circulating biochemical parameters with atherosclerosis localization and severity revealed a number of metabolic markers associated with the increased atherogenic potential. It is possible to distinguish both universal parameters that are associated with atherosclerosis, regardless of its localization and/or severity, and specific biomarkers that characterize either the localization or the severity of atherosclerosis, or both.

Background: Malaria is one of the most common human infections and continues to cause significant morbidity and mortality all over the world. To assess and compare the hematological changes in common types of malaria in our patients.Methods: This observational study included 100 diagnosed malaria patients of Multan Medical and Dental college, Multan both from out patient department (OPD) and in-patient department, between March 2020 and March 2021. The diagnosis of malaria was confirmed by thick and thin film stained with Geimsa’s staining for malaria parasite and plasmodium species and the parasite index (MPI) in some cases. Complete blood counts (CBCs) were performed and WBC differential was done on all cases.Results: The most common type of malarial parasite was Plasmodium vivax followed by Plasmodium falciparum and 89% of the patient had thrombocytopenia, 70 % anemia, 23% had leukopenia and 10% had raised WBC count. The mean parasite load was 1.275±0.629%, 20 % of the cases showed neutropenia, 40 % had lymphopenia and 40 % showed monocytopenia. Of all the cases 15 % had neutrophilia, 8 % had lymphocytosis and 5 % had eosinophilia. Thrombocytopenia was slightly more in P. falciparum (58.69%) than P. vivax (30.18%) cases, p&gt;0.05, whereas there was no significant difference in the incidence of anemia in two groups (34.68% vs 33.82%) with p&gt;0.05.Conclusions: P. vivax is the common malarial parasite in our population. Both P. vivax and P. falciparum can cause marked hematological changes including thrombocytopenia, anemia, lymphopenia and monocytopenia.

The objective of this study was to perform a systematic review of randomized controlled trials (RCTs) related to chronic urticaria in Indian patients evaluating different treatment options published in the last decade. A systematic literature search of PubMed/Medline was performed using keywords “Study(ti) OR trial(ti) AND urticaria(ti) AND “2009”(Date-Publication): “2020”(Date-Publication). All the selected articles were screened for author information and study design. Only RCTs from India were considered for the final analysis. Out of 205 articles retrieved, 11 RCTs were selected for the systematic review. Six RCTs evaluated the effects of antihistamines (loratadine, levocetirizine, rupatadine, and olopatadine) in Indian patients with chronic urticaria. The results show that these agents are effective and well tolerated in the treatment of chronic urticaria. Other therapies evaluated through RCTs included levocetirizine plus montelukast, add-on methotrexate, azathioprine, cyclosporine, narrowband ultraviolet B, psoralen plus ultraviolet A, and vitamin D. Levocetirizine 5 mg plus montelukast 10 mg combination was found to be as effective as levocetirizine 10 mg in patients not responding to levocetirizine 5 mg/day. A small trial did not prove the benefit of methotrexate add-on therapy with antihistamine. Azathioprine trials show that it can be a useful option in resource-limited settings. Second-generation antihistamines represent the most commonly investigated therapies through RCTs in India, and they represent a valuable option in the management of chronic urticaria.

Die fehlende Möglichkeit der kardialen Triggerung limitiert bisher die fetale Kardio-MRT. Ziel der Studie war die Evaluation eines neu entwickelten Doppler-Ultraschall Sensors zur Triggerung fetaler dynamischer Kardio-MRT Aufnahmen.

Intrigue, provocation, and the birth of independence: the Estonian foreign delegation and Aleksander Kesküla This article is an account of the relations between two groups working in Scandinavia in 1918 in order to attain foreign recognition of Estonian independence. The first of these was the official Estonian foreign delegation, headed by Jaan Tõnisson, which began its work in February 1918. The other group consisted for the most part of a single person: the emigré adventurer and self-styled politician Aleksander Kesküla who had been involved in quasi-diplomatic activities as a representative of Estonians since the beginning of the war. Due to the nature of the available sources, I am focusing on the delegation's viewpoint on the events described. I have tried to frame the basic difference between the delegation and Kesküla with the help of the notions of proto-diplomacy and para-diplomacy, as they have been used by Ivo D. Duchacek and others. The identity of the delegation, a proto-diplomatic body, was that of a foreign representation of Estonian Maapäev (the first ever representative body of the Estonian people). The delegation members' mandates, however, were vague and of doubtful authority since Maapäev had been dissolved and Estonia had been occupied by German forces. This situation made it almost impossible to get up-to-date instructions from the nearly dysfunctional provisional government in Estonia. The members of the delegation, all inexperienced in diplomacy, were correspondingly prone to passivity and – if not – to missteps. Kesküla as a para-diplomat was on the outside unconcerned with legalities and thought that his experience alone made him superior to his amateur colleagues, lack of mandate notwithstanding. Unlike the official delegation, he was well-connected and highly competent in the political affairs of Stockholm, which he could and would use against the delegation. The conflict between the delegation and Kesküla grew out of personal animosities, as well as the basic incompatibility between their viewpoints: one proto- and the other para-diplomatic. It began with the total failure of negotiations between Kesküla and Tõnisson, and was cemented by the delegation's public declaration that Kesküla had no right to act as a representative of Estonians. Kesküla's revenge was to spread rumors that some of the delegation members – particularly Jaan Tõnisson and Mihkel Martna, who also happened to be his personal enemies – were German-friendly, if not outright German agents. This could be "proved" in several ways: certainly by referring to their contacts with German ministers in Stockholm and Copenhagen, but also by raising suspicions of past contacts with German authorities. The intrigue was mostly arranged through the Embassy of France in Stockholm where Kesküla had good, long-term contacts with the minister Thiébaut and the "press attaché" André Waltz, and where he presented himself as the leader of an alternative, left-wing anti-German movement in Estonia. The first provisional de facto French recognition of the Estonian constitutive assembly, although sent to Tõnisson, had also been achieved at least partially thanks to Kesküla. Kesküla's schemes had the effect of exacerbating already-existing personal and political animosities inside the delegation. The naturally domineering personality of Tõnisson was one source of tension, another one was the orientation controversy between German-friendly and Ententefriendly members of the delegation. The main rift appeared between the members situated in Copenhagen (Tõnisson, Martna, Karl Menning, and occasionally Eduard Virgo) and those in Stockholm (Ferdinand Kull and Gustav Suits). Kull in particular was apt to demand more decisive action against Germany and began to consider himself something of a counterbalance to the delegation's German-friendliness, which provoked him to act increasingly on his own volition and eventually caused his expulsion. Any long-term effect of Kesküla's activities on the obtainment of Estonian independence and the development of Estonian statehood was probably negligible. All the same, the story illustrates well the problems facing the first Estonian diplomats, and their inherent vulnerability to intrigue and provocation. On a more positive note, the need to resist Kesküla's attacks also had the result of making the delegation tackle more decisively the delicate questions of its inner hierarchy, orientation vis à vis the belligerents and the overall course of action. Keywords: History of Estonia, First World War, Aleksander Kesküla, protodiplomacy. Mart Kuldkepp (b. 1983), Ph.D. student, Assistant Lecturer at the Department of Scandinavian Studies, University of Tartu. Correspondence: Mart Kuldkepp, Department of Scandinavian Studies, University of Tartu. Ülikooli 17, 51014, Tartu, Estonia. E-mail: Mart.Kuldkepp@ut.ee