Evaluation of the Incidence of Chronic Thromboembolic Pulmonary Hypertension 1 Year After First Episode of Acute Pulmonary Embolism: A Cohort Study

Purpose

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important complication after acute pulmonary embolism (PE) with considerable morbidity and mortality. The aim of this study was to estimate the CTEPH incidence in a cohort after the first occurrence of PE.

Methods

We conducted a 1-year follow-up cohort study between 2015 and 2018 to assess the incidence of CTEPH in 474 patients with their first acute episode of PE. For the diagnosis of CTEPH, patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography, right heart catheterization, ventilation-perfusion lung scanning, and CT pulmonary angiography.

Results

Overall, 317 patients were included in the study. The mean age of the patients was 56.5 ± 16 years. One hundred and three patients (32%) had exertional dyspnea at the 1-year follow-up. Patients with evidence of pulmonary hypertension (PH) on echocardiography underwent right heart catheterization. Eleven patients (18%) had no PH (mPAP < 25 mmHg); 47 patients (81%) had mPAP > 25 mmHg. Fifteen patients had PAWP > 15 mmHg, including those with underlying left heart problems or valvular diseases. There were 32 patients with PAH (mPAP > 25 mmHg and PVR > 3 WU) undergoing CTEPH studies; 22 patients (6.9%) had multiple segmental defects suggesting CTEPH on a perfusion scan.

Conclusion

The incidence of CTEPH observed in this study 1 year after the first episode of acute PE was approximately 6.9%. This incidence seems to be high in our population, and diagnostic and therapeutic strategies for the early identification of CTEPH are needed.

     

Worldwide prevalence of microbial agents’ coinfection among COVID‐19 patients: A comprehensive updated systematic review and meta‐analysis

BackgroundTo provide information about pathogens’ coinfection prevalence with SARS‐CoV‐2 could be a real help to save patients’ lives. This study aims to evaluate the pathogens’ coinfection prevalence among COVID‐19 patients.MethodIn order to find all of the relevant articles, we used systematic search approach. Research‐based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID‐19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed.ResultsA total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID‐19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95–26.46; I ²: 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31–18.96; I ²: 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84–17.36; I ²: 98.3%). Meta‐regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity.ConclusionWe identified a high prevalence of pathogenic microorganism coinfection among COVID‐19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID‐19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents’ coinfection with SARS‐CoV‐2.     

Protective effects of a magnesium magnetic isotope (Mg25)‐exchanging nanoparticle (25MgPMC16) on mitochondrial functional disorders in esmolol‐induced cardiac arrest in rats

1 In cardiac surgery, agents are needed to produce temporary cardiac arrest (cardioplegia). One of these agents is esmolol (ESM) which is a short‐acting selective beta‐1 adrenergic receptor antagonist and its overdose causes diastolic ventricular arrest. 2 The ²⁵MgPMC₁₆ (porphyrin adducts of cyclohexil fullerene‐C60) is known as a nanoparticle which has a cardioprotective effect when the heart is subjected to stressful conditions. 3 In this study, we aimed to confirm the deleterious effects of ESM overdose on cardiac mitochondria and identify any protective effects of ²⁵MgPMC₁₆ in male Wistar rats. Esmolol 100 mg kg^?1 (LD50 = 71 mg kg^?1) was injected intravenously (i.v.) into tail vein to induce cardiac arrest. This dose was obtained from an ESM dose–response curve which induces at least 80% arrest in rats. 4 ²⁵MgPMC₁₆ at three different doses (45, 90 and 224 mg kg^?1) was injected i.v. as pretreatment, eight hours before ESM injection. ²⁵MgCl₂ or ²⁴MgPMC₁₆ were used as controls. Following cardiac arrest, the heart was removed and the mitochondria extracted. Mitochondrial viability and the adenosine 5′‐diphosphate sodium salt hydrate/Adenosine 5′‐triphosphate disodium salt hydrate (ADP/ATP) ratio were measured as biomarkers of mitochondrial function. 5 Results indicate that ²⁵MgPMC₁₆ caused a significant increase in mitochondrial viability and decrease in ADP/ATP ratio. No significant changes were seen with ²⁴MgPMC₁₆ or ²⁵MgCl₂. It is concluded that cardiac arrest induced by ESM overdose leads to a significant decrease in mitochondrial viability and their ATP levels, whereas pretreatment by ²⁵MgPMC₁₆ can protect mitochondria by increasing ATP level through liberation of Mg into cells and the improvement of hypoxia.     

Role of cholecystokinin receptors in induction of antinociception in hot-plate test

In the present study, the antinociceptive effect of cholecystokinin receptor agonists in the hot-plate test in mice has been evaluated. Subcutaneous administration of cholecystokinin octapeptide (cholecystokinin-8; 0.001, 0.005, 0.01, 0.05, and 0.1 mg/kg), unsulfated cholecystokinin octapeptide (cholecystokinin-8U; 0.1 mg/kg) or caerulein (0.25 mg/kg) produced antinociception. Administration of the cholecystokinin tetrapeptide (cholecystokinin-4; 0.25, 0.5 and 1.0 mg/kg) had no effect in the hot-plate test. Subcutaneous injection of the selective cholecystokinin receptor antagonists, MK-329 (0.125, 0.25 and 0.5 mg/kg) or L-365,260 (0.125, 0.25 and 0.5 mg/kg), produced no antinociceptive response. When the animals were pretreated with the cholecystokinin receptor antagonists or naloxone (0.5 and 1 mg/kg), a significant decrease in the antinociceptive response induced by cholecystokinin-8 and caerulein was obtained. The results indicate that single administration of cholecystokinin receptor agonists could produce an antinociceptive effect which is probably mediated via cholecystokinin receptors. With respect to the results obtained from morphine and naloxone administration, it is concluded that there may be an interaction between cholecystokinin and opiate mechanisms.     

Antinociceptive effect of intracerebroventricular administration of cholecystokinin antagonist in nerve-ligated mice

In the present study we investigated the effects of intracerebroventricular injection of caerulein, the cholecystoki nin receptor agonist and proglumide, the receptor antagonist on morphine response in the sciatic nerve ligation in mice. Subcutaneous administration of morphine induced antinociception in the both intact and ligated mice, however, the response of the opioid was lower in the ligated mice as compared with the intact animals. Caerulein induced antinociception in the non-ligated but not in the nerve-ligated animals. Combination of caerulein with morphine elicited higher response in ligated animals, however, the response induced in ligated animals was much more prominent. Proglumide alone did not elicit any response in both animal groups. The antagonist decreased the response of caerulein in the nonligated mice. Low doses of proglumide in the combination with caerulein induced antinociception in the ligated mice. We conclude that cholecystokinin receptor mechanism(s) may alter morphine resistance induced by nerve ligation.     

Cholecystokinin and GABA interaction in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety

In the present study, we have investigated the effects and interaction of CCK and GABAergic systems in the dorsal hippocampus of rats using the elevated plus-maze test of anxiety. Bilateral injection of different doses of CCK(8s) (0.01, 0.05 and 0.1 microg/rat) into the dorsal hippocampus (intra-CA1) decreased percentage of open arm time (%OAT) and open arm entries (%OAE) that are representative of anxiogenic-like behavior. The bilateral injection of three doses of LY225910, a selective CCK2 receptor antagonist (0.01, 0.1 and 0.5 microg/rat) produced significant anxiolytic behavior. Although muscimol (GABA(A+)) (0.1, 0.5 and 1 microg/rat, intra-CA1) produced dose dependent increase in %OAT and a slight increase in %OAE, bicuculline (GABA(A-)), (1, 2 and 4 microg/rat, intra-CA1) failed to change the anxiety profile. Both muscimol (0.1 microg/rat) and bicuculline (1 microg/rat), when co-administered with LY225910, reversed the effect of latter drug on anxiety but when co-administered with CCK8s (0.05 microg/rat) showed no effect on anxiety profile. In conclusion, it seems that both CCK and GABAergic systems not only play a part in the modulation of anxiety in the dorsal hippocampus of rats but also have demonstrated a complex interaction as well.     

Recurrent Kaposi sarcoma of the ear in an HIV‐negative patient: A case report with review of the literature. Is ear a predilection site for Kaposi sarcoma in HIV‐negatives?

While Kaposi sarcoma (KS) of the head and neck is common in HIV‐positives, it is a rare presentation in HIV‐negatives. It is important to consider KS in the differential diagnosis of ear lesions in HIV‐negative patients.     

Interactions between Antinociception Induced by Cholecystokinin Antagonists and GABA Agonists in the Tail-Flick Test

Abstract: In this work, the influences of cholecystokinin receptor antagonists L-365,260, MK-329 and proglumide on antinociception induced by baclofen and GABA uptake inhibitor 4, 5, 6, 7–tetrahydroisoxazolo [4, 5-c]pyridin-3-ol (THPO) in the tail flick test has been studied. Baclofen and THPO induced antinociception in the tail flick test. Morphine, and the CCK receptor antagonists, MK-329, L-365,260 and proglumide also induced antinociception. The CCK receptor antagonists potentiated antinociceptive response induced by both baclofen and THPO. It may be concluded that cholecystokinin receptor mechanism(s) may interact with antinociception induced by GABA receptor mechanism(s).