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Emergencias : Revista de La Sociedad... Oct 2023Tools to identify patients with mild to moderate COVID-19 are as yet unavailable. Our aims were to identify factors associated with nonadverse outcomes and develop a...
OBJECTIVES
Tools to identify patients with mild to moderate COVID-19 are as yet unavailable. Our aims were to identify factors associated with nonadverse outcomes and develop a scale to predict nonadverse evolution in patients with COVID-19 (the CoNAE scale) in hospital emergency departments.
MATERIAL AND METHODS
Retrospective cohort study of patients who came to one of our area's national health service hospitals for treatment of SARS-CoV-2 infection from July 1, 2020, to July 31, 2021. From case records we collected sociodemographic information, underlying comorbidity and ongoing treatments, other relevant medical history details, and vital constants on arrival for triage. Multilevel multivariable logistic regression models were used to identify predictors.
RESULTS
The model showed that patients who had nonadverse outcomes were younger, female, and vaccinated against COVID-19 (2 doses at the time of the study). They arrived with normal vital signs (heart rate, diastolic and systolic pressures, temperature, and oxygen saturation) and had none of the following concomitant diseases or factors: heart failure other heart disease, hypertension, diabetes, liver disease, dementia, history of malignant tumors, and they were not being treated with oral or other systemic corticosteroids or immunosuppressant therapy. The area under the receiver operating characteristic curve for the model was 0.840 (95% CI, 0.834-0.847).
CONCLUSION
We developed the CoNAE scale to predict nonadverse outcomes. This scale may be useful in triage for evaluating patients with COVID-19. It may also help predict safe discharge or plan the level of care that patients require not only in a hospital emergency department but also in urgent primary care settings or out-of-hospital emergency care.
Topics: Humans; Female; COVID-19; SARS-CoV-2; Retrospective Studies; State Medicine; Emergency Medical Services
PubMed: 37801415
DOI: 10.55633/s3me/E024.2023 -
International Journal of Molecular... Mar 2024While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart... (Review)
Review
While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart failure, prognoses and survival rates are much worse in PAH. Patients with PAH are at a higher risk of developing supraventricular arrhythmias and malignant ventricular arrhythmias. The latter underlie sudden cardiac death regardless of the mechanical cardiac dysfunction. Systemic chronic inflammation and oxidative stress are causal factors that increase the risk of the occurrence of cardiac arrhythmias in hypertension. These stressful factors contribute to endothelial dysfunction and arterial pressure overload, resulting in the development of cardiac pro-arrhythmic conditions, including myocardial structural, ion channel and connexin43 (Cx43) channel remodeling and their dysfunction. Myocardial fibrosis appears to be a crucial proarrhythmic substrate linked with myocardial electrical instability due to the downregulation and abnormal topology of electrical coupling protein Cx43. Furthermore, these conditions promote ventricular mechanical dysfunction and heart failure. The treatment algorithm in HTN is superior to PAH, likely due to the paucity of comprehensive pathomechanisms and causal factors for a multitargeted approach in PAH. The intention of this review is to provide information regarding the role of Cx43 in the development of cardiac arrhythmias in hypertensive heart disease. Furthermore, information on the progress of therapy in terms of its cardioprotective and potentially antiarrhythmic effects is included. Specifically, the benefits of sodium glucose co-transporter inhibitors (SGLT2i), as well as sotatercept, pirfenidone, ranolazine, nintedanib, mirabegron and melatonin are discussed. Discovering novel therapeutic and antiarrhythmic strategies may be challenging for further research. Undoubtedly, such research should include protection of the heart from inflammation and oxidative stress, as these are primary pro-arrhythmic factors that jeopardize cardiac Cx43 homeostasis, the integrity of intercalated disk and extracellular matrix, and, thereby, heart function.
Topics: Humans; Connexin 43; Pulmonary Arterial Hypertension; Arrhythmias, Cardiac; Anti-Arrhythmia Agents; Cardiac Conduction System Disease; Familial Primary Pulmonary Hypertension; Hypertension; Heart Failure; Inflammation
PubMed: 38542257
DOI: 10.3390/ijms25063275 -
Frontiers in Oncology 2023To explore the factors influencing the successful implementation of same-day discharge in patients undergoing minimally invasive hysterectomy for malignant and... (Review)
Review
Factors influencing same-day discharge after minimally invasive hysterectomy for malignant and non-malignant gynecological diseases: a systematic review and meta-analysis.
OBJECTIVE
To explore the factors influencing the successful implementation of same-day discharge in patients undergoing minimally invasive hysterectomy for malignant and non-malignant gynecological diseases.
METHOD
We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and Clinical Trials.gov from inception to May 23, 2023. We included case-control and cohort studies published in English reporting same-day discharge factors in patients undergoing minimally invasive hysterectomy for malignant and non-malignant gynecological diseases. STATA 16.0 was used for the meta-analysis. Risk factors were assessed using odds ratios (OR) (relative risk (RR)/hazard ratios (HR)) with 95% confidence intervals (CI), and logistic regression determined the same-day discharge rate (%).
RESULTS
We analyzed 29 studies with 218192 patients scheduled for or meeting same-day discharge criteria. The pooled rates were 50% (95% CI 0.46-0.55), and were similar for malignant and non-malignant gynecological diseases (48% and 47%, respectively). In terms of basic characteristics, an increase in age (OR: 1.03; 95% CI: 1.01-1.05), BMI (OR: 1.02; 95% CI: 1.01-1.03), and comorbidities including diabetes and lung disease were risk factors affecting SDD, while previous abdominal surgery history (OR: 1.54; 95% CI: 0.93-2.55) and hypertension (OR: 1.53; 95% CI: 0.80-2.93) appeared not to affect SDD. In terms of surgical characteristics, radical hysterectomy (OR: 3.46; 95% CI: 1.90-6.29), surgery starting after 14:00 (OR: 4.07; 95% CI: 1.36-12.17), longer surgical time (OR: 1.03; 95% CI: 1.01-1.06), intraoperative complications (OR: 4.68; 95% CI: 1.78-12.27), postoperative complications (OR: 3.97; 95% CI: 1.68-9.39), and surgeon preference (OR: 4.47; 95% CI: 2.08-9.60) were identified as risk factors. However, robotic surgery (OR: 0.44; 95% CI: 0.14-1.42) and intraoperative blood loss (OR: 1.16; 95% CI: 0.98-1.38) did not affect same-day discharge.
CONCLUSIONS
An increase in age, body mass index, and distance to home; certain comorbidities (e.g., diabetes, lung disease), radical hysterectomy, surgery starting after 14:00, longer surgical time, operative complications, and surgeon preference were risk factors preventing same-day discharge. Same-day discharge rates were similar between malignant and non-malignant gynecological diseases. The surgery start time and body mass index have a greater impact on same-day discharge for malignant diseases than non-malignant diseases.
PubMed: 38264751
DOI: 10.3389/fonc.2023.1307694 -
Journal of Neuroimmunology Sep 2023Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS).
BACKGROUND
Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS).
OBJECTIVES
To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS).
METHODS
A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries.
RESULTS
We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment.
CONCLUSION
Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals.
Topics: Humans; Cladribine; Multiple Sclerosis; Immunosuppressive Agents; Retrospective Studies; Multiple Sclerosis, Relapsing-Remitting; Neoplasm Recurrence, Local; Tablets
PubMed: 37536052
DOI: 10.1016/j.jneuroim.2023.578164 -
Annals of Palliative Medicine Apr 2024Malignant ascites (MA) is common in patients with advanced cancer, and about 60% of patients with MA experience distressing symptoms. In addition, MA has been identified...
BACKGROUND AND OBJECTIVE
Malignant ascites (MA) is common in patients with advanced cancer, and about 60% of patients with MA experience distressing symptoms. In addition, MA has been identified as a poor prognostic factor, therefore, making the management of MA an important issue. We aimed to review literature describing MA provide a narrative synthesis of relevant studies.
METHODS
A literature search of articles published between 1971 and May 2023 was performed in PubMed, and Cochrane library using the words "ascites/malignant ascites" and the theme of each section. Authors independently selected the articles used and summarized. Finally, this manuscript was obtained consensus through discussed among all authors.
KEY CONTENT AND FINDINGS
The pathophysiological mechanism of ascites formation involves increased vascular permeability and impaired fluid drainage through the lymphatic system, which explain the occurrence of peritoneal carcinomatosis, portal hypertension due to liver tumors, liver cirrhosis in the background of hepatocellular carcinoma, and Budd-Chiari syndrome caused by tumor occlusion of the hepatic vein. The efficacy and safety of various treatments and procedures have been investigated previously; however, no treatment guidelines have been established yet. Diuretics and paracentesis are often selected as the first lines of treatment. Intraperitoneal drug administration (catumaxomab, bevacizumab, aflibercept, hyperthermic intraperitoneal chemotherapy, triamcinolone), indwelling peritoneal catheters, peritoneovenous shunting, and cell-free and concentrated ascites reinfusion therapy are commonly used to manage refractory ascites. A new device for this purpose is alfapump, which transfers ascites fluid from the peritoneum into the urinary bladder. In addition, thoracic epidural analgesia may be effective for managing ascites-related symptoms.
CONCLUSIONS
Despite these options, no standard treatment for MA has been established yet because few trials have been conducted in this area. There are many issues to be investigated, and future research and treatment development are expected.
PubMed: 38644553
DOI: 10.21037/apm-23-554 -
European Journal of Medical Research Oct 2023The main symptoms of preeclampsia (PE), a specific ailment that develops during pregnancy, are proteinuria and hypertension. The pathological root of the onset and...
BACKGROUND
The main symptoms of preeclampsia (PE), a specific ailment that develops during pregnancy, are proteinuria and hypertension. The pathological root of the onset and progression of PE is widely regarded as abnormal placental trophoblast cell function. This study aimed to look into the character and mechanism of Placenta-specific 8 (PLAC8) in trophoblast cell invasion and migration.
METHODS
Expressions of PLAC8 and AlkB homologue 5 (ALKBH5) were examined by western blot and quantitative real-time PCR. The m6A level of PLAC8 mRNA was detected by methylated RNA Immunoprecipitation. Using Transwell experiments, cell invasion and migration were examined. The enzyme-linked immunosorbent assay was utilized to analyze the MMP-2 and MMP-9 secretion levels. RNA pull-down and RNA immunoprecipitation were conducted to detect the binding between ALKBH5 and PLAC8.
RESULTS
In PE tissue and hypoxia-treated HTR-8/SVneo cells, levels of ALKBH5 and PLAC8 were increased, and PLAC8 m6A methylation levels were decreased. There was a positive correlation between PLAC8 and ALKBH5 expression in clinical tissues. In addition, overexpressing PLAC8 promoted HTR-8/SVneo cell migration and invasion, and so as the levels of MMP-2 and MMP-9; while interference with PLAC8 reduced the migration and invasion of hypoxia-treated HTR-8/SVneo cells, and so as the levels of MMP-2 and MMP-9. Moreover, the PLAC8 mRNA's m6A modification site was GAACU (Position 1449, Site 2). Increased levels of MMP-2 and MMP-9, as well as migration and invasion of HTR-8/SVneo cells exposed to hypoxia, were all facilitated by the m6A Site2 mutation. Furthermore, ALKBH5 could bind to PLAC8, reduce its m6A modification, and promote its expression.
CONCLUSION
High-expressed ALKBH5 inhibits the m6A level of PLAC8 mRNA and promotes PLAC8 expression, while PLAC8 overexpression can promote hypoxia-induced invasion and migration of HTR-8/Svneo cells, indicating its potential protective function in PE.
Topics: Humans; Pregnancy; Female; Up-Regulation; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Cell Line; Pre-Eclampsia; Trophoblasts; Placenta; Cell Movement; RNA; RNA, Messenger; Hypoxia; Proteins
PubMed: 37885015
DOI: 10.1186/s40001-023-01442-7 -
Frontiers in Pharmacology 2023Malignant melanoma is a highly aggressive cancer that spreads and metastasizes quickly. In recent years, the antiangiogenic drug bevacizumab has been trialed to treat...
Efficacy and safety of bevacizumab in patients with malignant melanoma: a systematic review and PRISMA-compliant meta-analysis of randomized controlled trials and non-comparative clinical studies.
Malignant melanoma is a highly aggressive cancer that spreads and metastasizes quickly. In recent years, the antiangiogenic drug bevacizumab has been trialed to treat malignant melanoma. We conducted the first meta-analysis to examine the efficacy and safety of bevacizumab combined with other drugs in malignant melanoma. We searched for randomized controlled trials (RCTs) and non-comparative clinical studies of bevacizumab combined with chemotherapy, targeted medicine, and interferon to treat malignant melanoma in PubMed, Embase, the Cochrane Library, and Web of Science. Meta-analysis of RCT was performed using Review Manager (version 5.4), and non-comparative meta-analysis was performed using R (version 4.0.3). The primary outcome was the objective response rate. Depending on the heterogeneity of the included studies, the pooled outcomes and 95% CI were calculated using either random-effects or fixed-effect models. Subgroup outcomes were calculated with possible relevant variables. Sensitivity analyses were carried out by excluding each study from the highly heterogeneous pooled results in turn. Funnel plot and Begg's test were used to test the included studies' potential publication bias. The level of significance was set at < 0.05. This meta-analysis included 20 trials: five RCTs and 15 non-comparative clinical studies with a total of 23 bevacizumab intervention arms. In 14 treatment arms, bevacizumab was combined with chemotherapy drugs such as fotemustine, dacarbazine, carboplatin/paclitaxel, and temozolomide. In six treatment arms, bevacizumab was combined with targeted medicines such as imatinib, everolimus, sorafenib, erlotinib, and temsirolimus. There were also six treatment arms that used bevacizumab in combination with interferon. The pooled objective response rate was 15.8% (95% CI, 11.4%-20.2%). Bevacizumab plus carboplatin/paclitaxel significantly increased the overall survival compared to carboplatin/paclitaxel (HR = 0.64, 95% CI, 0.49-0.85, < 0.01). Fatigue, nausea, leukopenia, thrombocytopenia, and neutropenia were the most common adverse events. The pooled incidence of hypertension of all bevacizumab arms in malignant melanoma was 32.4% (95% CI, 24.5%-40.3%). This study showed that bevacizumab combined with chemotherapy might be effective and well-tolerated in patients with stage III or IV unresectable malignant melanoma. : [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=304625], identifier [CRD42022304625].
PubMed: 37521468
DOI: 10.3389/fphar.2023.1163805 -
Journal of Hypertension May 2024Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and...
BACKGROUND
Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and efficiently improving treatment and control of hypertension. We aimed to identify, characterize, and critically appraise hypertension STPs.
METHODS
We defined STP as a series of steps for the pharmacological treatment of primary hypertension, with information on target population, BP threshold for treatment initiation, target BP, specific drugs/classes/doses, and follow-up frequency. STPs for adult patients were identified from the websites of relevant health organizations, Google search, and through expert consultations (until July 2023). STPs for secondary, gestational, or malignant hypertension or those that were templates/samples were excluded. Included STPs were critically appraised using HEARTS in the Americas Checklist for hypertension management in primary care and compared with the 2021 WHO hypertension management guideline recommendations.
RESULTS
Fifty STPs were identified. All STPs had a stepwise treatment approach, involved guideline-recommended first-line drugs, and 98% consisted of at least four steps. Majority (54%) recommended monotherapy with calcium channel blockers as first-line treatment. Only 44% STPs recommended treatment initiation with combination therapy, and 16% recommended single-pill combinations. Most (62%) had dose-intensification as the second step. Most (74%) STPs did not provide complete dosing information. Only one STP mentioned a target time for achieving BP control. On average, STPs scored a performance of 68% on the HEARTS Checklist.
CONCLUSION
Several STPs are available globally; however, most of them have enormous scope for improvement through interventions aimed at alignment with the latest evidence-based guidelines and multistakeholder engagement.
Topics: Adult; Humans; Antihypertensive Agents; Hypertension; Calcium Channel Blockers; Combined Modality Therapy; Clinical Protocols
PubMed: 38108382
DOI: 10.1097/HJH.0000000000003636 -
Annals of Surgical Oncology Jul 2024Up to 41% of intra- and extra-adrenal paragangliomas are linked to germline mutations with autosomal dominant transmission, which necessitates genetic testing for...
BACKGROUND
Up to 41% of intra- and extra-adrenal paragangliomas are linked to germline mutations with autosomal dominant transmission, which necessitates genetic testing for patients and their relatives. Certain alterations, such as the succinate dehydrogenase (SDH) subunit B gene mutation, are associated with a significant risk of extra-adrenal, malignant, and metastatic disease forms. This highlights the need for routine genetic counseling and diligent surveillance, as well as surgeon awareness of hereditary paraganglioma-pheochromocytoma syndrome (HPPS).
METHODS
We present a multimedia article featuring a step-by-step video of a complex retroperitoneal resection, enriched with perioperative management insights.
RESULTS
A 17-year-old female presented with episodes of hypertension, tachycardia, and diffuse diaphoresis. CT revealed a paraaortic mass adjacent to the left renal hilum later confirmed by a SPECT/CT with iodine-123 meta-iodobenzylguanidine. Additional imaging with gallium-68 DOTATATE was not performed then due to unknown mutation status. The patient underwent robotic removal of the tumor and adjacent lymph nodes. Pathology confirmed a poorly differentiated paraganglioma with 0/6 lymph node metastases. Genetic tests revealed SDHB gene mutation, indicative of HPPS. At 12 months, the patient remained disease-free on CT with normalized metanephrines levels and no detectable circulating tumor DNA. Familial screening detected her mother, maternal uncle, and maternal grandfather to be SDHB mutation carriers, although phenotypically silent.
CONCLUSIONS
Robotic-assisted resection can be safe and effective for retroperitoneal malignant paragangliomas. However, management extends beyond surgery and requires cascade genetic testing to address familial risks. Because of the high probability of cancer associated with SDHB mutation, lifelong patient surveillance is imperative.
Topics: Humans; Female; Adolescent; Paraganglioma, Extra-Adrenal; Robotic Surgical Procedures; Retroperitoneal Neoplasms; Prognosis; Pheochromocytoma
PubMed: 38615151
DOI: 10.1245/s10434-024-15267-z -
The American Journal of Case Reports Aug 2023BACKGROUND Hypertensive crisis is a relatively common condition often due to uncontrolled essential hypertension, but also potentially driven by one of many possible...
BACKGROUND Hypertensive crisis is a relatively common condition often due to uncontrolled essential hypertension, but also potentially driven by one of many possible secondary etiologies. In this report, we detail a case of new-onset resistant hypertension leading to hypertensive emergency complicated by myocardial infarction and congestive heart failure secondary to underlying cortisol-producing metastatic adrenocortical carcinoma. CASE REPORT A 57-year-old woman with no past medical history presented with generalized weakness and weight gain. Her blood pressure was 239/141 with a pulse of 117. Other vital signs were normal. A physical exam was notable for obesity and lower-extremity edema. Initial serum investigations were notable for leukocytosis, hypokalemia, metabolic alkalosis, and elevated troponin and BNP. An ECG showed anterolateral ST depression and left ventricular hypertrophy. A coronary angiogram revealed no coronary artery disease. Her ejection fraction was 25% by echocardiogram. Further investigation revealed severely elevated serum cortisol levels. CT scans were notable for left adrenal mass with evidence of hepatic, lung, and bone metastasis. A liver biopsy confirmed metastatic adrenocortical carcinoma. The patient was started on antihypertensives and a steroidogenesis inhibitor, with improvement in her blood pressure. She received palliative chemotherapy but later elected to pursue hospice care. CONCLUSIONS This report highlights the potential for underlying cortisol excess and adrenocortical carcinoma as a potential secondary etiology of resistant hypertension and hypertensive crisis. Due to the aggressive nature of this tumor, as demonstrated in this patient, a high index of suspicion and prompt attention are required for patients presenting with these clinical manifestations.
Topics: Female; Humans; Middle Aged; Adrenocortical Carcinoma; Hydrocortisone; Hypertension, Malignant; Hypertension; Adrenal Cortex Neoplasms
PubMed: 37605388
DOI: 10.12659/AJCR.940228