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Journal of Gastrointestinal and Liver... Jun 2024During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19...
BACKGROUND AND AIMS
During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection developed secondary sclerosing cholangitis (SSC) as a hepatobiliary complication.
METHODS
17 patients were endoscopically diagnosed and treated with COVID-19 SSC from February 2020 until October 2022 at our center. We retrospectively reviewed and analyzed the data to define risk factors, establish endoscopic treatment options, and to estimate incidence and outcomes.
RESULTS
258 patients with COVID-19 infection were admitted to our tertiary center and mechanically ventilated. 10 patients developed COVID-19 SSC in-house, and 7 patients were transferred for further endoscopic treatment. All 17 patients were mechanically ventilated, received vasoactive substances and 12 of them were treated with extracorporeal membrane oxygenation therapy. Endoscopic retrograde cholangiography (ERC) was performed in all patients to establish the diagnosis of COVID-19 SSC and evaluate endoscopic treatment options. All ERCs revealed biliary casts. 9 patients had developed severe rarefication of the intrahepatic bile ducts and 4 showed biliary strictures. As endoscopic treatment approaches, casts were removed repeatedly, and strictures were dilated. During the study period, 14 patients died (82%). 3 patients are in follow-up to reassess the need for liver transplantation.
CONCLUSIONS
COVID-19 SSC was observed in 2.6 % of the patients with severe COVID-19 in our center. We show that endoscopic approaches offer the opportunity to extract casts and to treat biliary strictures. As the mortality rate of COVID-19 SSC is high, endoscopic treatment can be of great clinical relevance as a bridge to liver transplantation.
Topics: Humans; COVID-19; Male; Female; Cholangitis, Sclerosing; Middle Aged; Retrospective Studies; Cholangiopancreatography, Endoscopic Retrograde; Tertiary Care Centers; Aged; SARS-CoV-2; Adult; Treatment Outcome; Risk Factors; Liver Transplantation
PubMed: 38944874
DOI: 10.15403/jgld-5476 -
Frontiers in Neurology 2024Migraine, a prevalent neurological disorder, affects approximately 14.1% of the global population and disproportionately impacts females. This debilitating condition... (Review)
Review
Migraine, a prevalent neurological disorder, affects approximately 14.1% of the global population and disproportionately impacts females. This debilitating condition significantly compromises quality of life, productivity, and incurs high healthcare costs, presenting a challenge not only to individuals but to societal structures as a whole. Despite advances in our understanding of migraine pathophysiology, treatment options remain limited, necessitating ongoing research into effective therapies. This review delves into the complexity of migraine management, examining the roles of genetic predisposition, environmental influences, personalized treatment approaches, comorbidities, efficacy and safety of existing acute and preventive treatments. It further explores the continuum between migraine and tension-type headaches and discusses the intricacies of treating various migraine subtypes, including those with and without aura. We emphasize the recent paradigm shift toward trigeminovascular activation and the release of vasoactive substances, such as calcitonin gene-related peptide (CGRP), which offer novel therapeutic targets. We assess groundbreaking clinical trials, pharmacokinetic and pharmacodynamic perspectives, safety, tolerability, and the real-world application of CGRP monoclonal antibodies and gepants. In the face of persisting treatment barriers such as misdiagnosis, medication overuse headaches, and limited access to specialist care, we discuss innovative CGRP-targeted strategies, the high cost and scarcity of long-term efficacy data, and suggest comprehensive solutions tailored to Turkiye and developing countries. The review offers strategic recommendations including the formulation of primary care guidelines, establishment of specialized outpatient clinics, updating physicians on novel treatments, enhancing global accessibility to advanced therapies, and fostering patient education. Emphasizing the importance of lifestyle modifications and holistic approaches, the review underscores the potential of mass media and patient groups in disseminating critical health information and shaping the future of migraine management.
PubMed: 38938785
DOI: 10.3389/fneur.2024.1402569 -
Scientific Reports Jun 2024The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum...
The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum norepinephrine (NE) dosage (MND) and mortality in neonates with septic shock. This retrospective cohort study included neonates with evidence of septic shock and those who received NE infusion. The study included 123 neonates, with 106 in the survival group and 17 in the death group. The death group exhibited significantly lower birth weight (p = 0.022), 1-min Apgar score (p = 0.005), serum albumin (p < 0.001), and base excess (BE) (p = 0.001) levels, but higher lactate (LAC) levels (p = 0.009) compared to the survival group. MND demonstrated an ROC area under the curve of 0.775 (95% CI 0.63-0.92, p < 0.001) for predicting mortality, with an optimal threshold of 0.3 µg/(kg·min), a sensitivity of 82.4%, and a specificity of 75.5%. Multivariate logistic regression indicated that an MND > 0.3 µg/(kg·min) (OR, 12.08, 95% CI 2.28-64.01) was associated with a significantly higher mortality risk. Spearman rank correlation showed a positive correlation between MND and LAC (r = 0.252, p = 0.005), vasoactive-inotropic score (VIS) (r = 0.836, p < 0.001), and a negative correlation with BE (r = - 0.311, p = 0.001). MND > 0.3 µg/(kg min) is a useful predictive marker of mortality in neonatal septic shock.
Topics: Humans; Shock, Septic; Infant, Newborn; Norepinephrine; Male; Female; Retrospective Studies; ROC Curve; Apgar Score
PubMed: 38937631
DOI: 10.1038/s41598-024-65744-4 -
Pediatric Critical Care Medicine : a... Jun 2024Transcutaneous carbon dioxide (Tcco2) monitoring can noninvasively assess ventilation by estimating carbon dioxide (CO2) levels in the blood. We aimed to evaluate the...
OBJECTIVES
Transcutaneous carbon dioxide (Tcco2) monitoring can noninvasively assess ventilation by estimating carbon dioxide (CO2) levels in the blood. We aimed to evaluate the accuracy of Tcco2 monitoring in critically ill children by comparing it to the partial pressure of arterial carbon dioxide (Paco2). In addition, we sought to determine the variation between Tcco2 and Paco2 acceptable to clinicians to modify patient care and to determine which patient-level factors may affect the accuracy of Tcco2 measurements.
DESIGN
Retrospective observational cohort study.
SETTING
Single, quaternary care PICU from July 1, 2012, to August 1, 2020.
PATIENTS
Included participants were admitted to the PICU and received noninvasive ventilation support (i.e., continuous or bilevel positive airway pressure), conventional mechanical ventilation, or high-frequency oscillatory or percussive ventilation with Tcco2 measurements obtained within 15 minutes of Paco2 measurement.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Three thousand four hundred seven paired arterial blood gas and Tcco2 measurements were obtained from 264 patients. Bland-Altman analysis revealed a bias of -4.4 mm Hg (95% CI, -27 to 18.3 mm Hg) for Tcco2 levels against Paco2 levels on the first measurement pair for each patient, which fell within the acceptable range of ±5 mm Hg stated by surveyed clinicians, albeit with wide limits of agreement. The sensitivity and specificity of Tcco2 to diagnose hypercarbia were 93% and 71%, respectively. Vasoactive-Infusion Score (VIS), age, and self-identified Black/African American race confounded the relationship between Tcco2 with Paco2 but percent fluid overload, weight-for-age, probe location, and severity of illness were not significantly associated with Tcco2 accuracy.
CONCLUSIONS
Tcco2 monitoring may be a useful adjunct to monitor ventilation in children with respiratory failure, but providers must be aware of the limitations to its accuracy.
PubMed: 38935571
DOI: 10.1097/PCC.0000000000003564 -
Frontiers in Pharmacology 2024Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and...
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial.
Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (C) and the area under the concentration-time curve (AUC) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. http://www.chinadrugtrials.org.cn, identifier CTR20210064.
PubMed: 38933676
DOI: 10.3389/fphar.2024.1359939 -
Diagnostics (Basel, Switzerland) Jun 2024Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin... (Review)
Review
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin A (CgA), pancreatic polypeptide (PP), and neuron-specific enolase (NSE) have limitations in terms of specificity and sensitivity. Specific circulating markers such as serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and various gastrointestinal hormones such as gastrin, glucagon, somatostatin, and vasoactive intestinal peptide (VIP) have a role in identifying functional NENs. Recent advances in molecular and biochemical markers, also accounting for novel genomic and proteomic markers, have significantly improved the landscape for the diagnosis and monitoring of NENs. This review discusses these developments, focusing on both traditional markers such as CgA and NSE, as well as specific hormones like gastrin, insulin, somatostatin, glucagon, and VIP. Additionally, it covers emerging genomic and proteomic markers that are shaping current research. The clinical applicability of these markers is highlighted, and their role in improving diagnostic accuracy, predicting surgical outcomes, and monitoring response to treatment is demonstrated. The review also highlights the need for further research, including validation of these markers in larger studies, development of standardized assays, and integration with imaging techniques. The evolving field of biochemical markers holds promise for improving patient outcomes in the treatment of NENs, although challenges in standardization and validation remain.
PubMed: 38928704
DOI: 10.3390/diagnostics14121289 -
International Journal of Developmental... Jun 2024Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder...
Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder (ASD) often experience gastrointestinal problems and dysbiosis in their gut microbiota. Our previous study revealed that SMPS interventions had an impact on the gut microbiota of valproic acid (VPA)-induced autism model rats. However, the effects of SMPS on the behavior and gut function of autism model rats remain poorly understood. Therefore, we gave different doses of SMPS intervention in the early stage of autism model rats to observe their developmental conditions and behavior performances. Through histological evaluation and real-time polymerase chain reaction (PCR), integrity of the intestinal structure and the expression of tight junction-related gene Zo-1 and Occludin were detected. The results indicated that SMPS intervention improved the physical development, learning and memory impairment, and social performance of autism model rats. Meanwhile, SMPS promoted intestinal peristalsis and restored the integrity of the intestinal structure, reduced the number of inflammatory cells, and increased the expression of the Zo-1 and Occludin genes. Furthermore, the expression levels of neurotransmitters (substance P, enkephalin, vasoactive intestinal peptide, and 5-hydroxytryptamine) in the hippocampal tissues were altered after SMPS treatment. In conclusion, SMPS could ameliorate ASD-like phenotypes and gut problems in autism model rats. Collectively, these results provide new evidence for the relationship between the gut-brain axis and ASD and suggest a novel therapeutic target for ASD treatment.
PubMed: 38923604
DOI: 10.1002/jdn.10354 -
BJOG : An International Journal of... Jun 2024Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains...
OBJECTIVE
Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes.
DESIGN
Superiority, double-blind randomised controlled trial.
SETTING
A total of 20 UK fetal medicine units.
POPULATION
Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22 and 29 weeks of gestation.
METHODS
Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation.
MAIN OUTCOME MEASURES
All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85.
RESULTS
In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm).
CONCLUSIONS
Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.
PubMed: 38923115
DOI: 10.1111/1471-0528.17888 -
Journal of Cardiovascular Pharmacology Apr 2024Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may...
Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may have a nonhemostatic role. We characterized thrombin expression and vasoactivity in brain cerebral parenchymal arterioles (PAs) in rat models of pregnancy and PE. PAs were isolated and pressurized from nonpregnant (NP), late-pregnant (LP) rats and rats with experimental preeclampsia (ePE). Reactivity to thrombin (1-50 U/mL) was measured in the absence and presence of inhibition of cyclooxygenase (COX) and nitric oxide synthase (NOS). Plasma levels of prothrombin, thrombin-antithrombin (TAT), tissue plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) and cerebrospinal fluid (CSF) levels of TAT were compared via ELISA. Expression of protease-activated receptor (PAR) types 1 and 2 in PAs were measured by Western blot and immunohistochemistry. Neuronal thrombin expression was quantified in brains from all groups by immunohistochemistry. Prothrombin and TAT were elevated in ePE plasma compared to NP and LP. TAT was detected in CSF from all groups and significantly elevated in LP (NP: 0.137±0.014 ng/mL, LP: 0.241±0.015 ng/mL, ePE: 0.192±0.028 ng/mL; p<0.05). Thrombin caused modest vasoconstriction in PAs from all groups regardless of COX or NOS inhibition. PAR1 and PAR2 were found in PAs from all groups co-localized to smooth muscle. Thrombin expression in central neurons was decreased in both LP and ePE groups compared to NP. These findings suggest a role for thrombin and other hemostatic changes during pregnancy and PE beyond coagulation.
PubMed: 38922586
DOI: 10.1097/FJC.0000000000001579 -
Journal of the Saudi Heart Association 2024Incidence and outcomes of acute kidney injury (AKI) among neonates who underwent open-heart surgery are not well highlighted in the literature. We aim to assess the...
BACKGROUND
Incidence and outcomes of acute kidney injury (AKI) among neonates who underwent open-heart surgery are not well highlighted in the literature. We aim to assess the incidence, risk factors, and outcome of AKI among neonates undergoing open-heart surgery.
METHODS
This is a retrospective cohort study between 2016 and 2021 for all neonates requiring open heart surgery. The cases were divided into 2 groups: the AKI (index) group and the non-AKI (control) group. The two groups were statistically compared for risk factors, needs for dialysis, and outcomes.
RESULTS
100 patients fulfilled the inclusion criteria. Among them, 74 (74%) developed AKI, including 41 (55%), 15 (21%), and 18 (24%) patients in KDIGO stages 1, 2, and 3, respectively. Multivariate analysis comparing both groups demonstrated that low pre-operative creatinine (p = 0.01), prolonged bypass time (p = 0.0004) and high vasoactive inotropic score (VIS), (p = 0.0008) were risk factors for developing AKI post-operatively. Furthermore, in the AKI group, 17 (23%) neonates required renal replacement therapy in the form of peritoneal dialysis. The length of stay was higher in the AKI index group (p = 0.015). Patients who had AKI recovered their kidney function at discharge. There was no difference in mortality between both groups.
CONCLUSION
The AKI occurred in 74% of neonates undergoing open-heart surgery, with 23% of them needing peritoneal dialysis. Low pre-operative creatinine, high VIS score, and prolonged bypass time are potential risk factors for AKI development after neonatal open-heart surgery. AKI may lead to prolonged hospitalization, though most affected patients recovered their normal kidney function at discharge.
PubMed: 38919507
DOI: 10.37616/2212-5043.1374