A Comprehensive Systematic Review of the Latest Management Strategies for Hepatorenal Syndrome: A Complicated Syndrome to Tackle.

Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.

GDE6 promotes progenitor identity in the vertebrate neural tube.

The generation of neurons in the central nervous system is a complex, stepwise process necessitating the coordinated activity of mitotic progenitors known as radial glia. Following neural tube closure, radial glia undergo a period of active proliferation to rapidly expand their population, creating a densely packed neurepithelium. Simultaneously, radial glia positioned across the neural tube are uniquely specified to produce diverse neuronal sub-types. Although these cellular dynamics are well studied, the molecular mechanisms governing them are poorly understood. The six-transmembrane Glycerophosphodiester Phosphodiesterase proteins (GDE2, GDE3, and GDE6) comprise a family of cell-surface enzymes expressed in the embryonic nervous system. GDE proteins can release Glycosylphosphatidylinositol-anchored proteins from the cell surface via cleavage of their lipid anchor. GDE2 has established roles in motor neuron differentiation and oligodendrocyte maturation, and GDE3 regulates oligodendrocyte precursor cell proliferation. Here, we describe a role for GDE6 in early neural tube development. Using RNAscope, we show that Gde6 mRNA is expressed by ventricular zone progenitors in the caudal neural tube. Utilizing in-ovo electroporation, we show that GDE6 overexpression promotes neural tube hyperplasia and ectopic growths of the neurepithelium. At later stages, electroporated embryos exhibit an expansion of the ventral patterning domains accompanied by reduced cross-repression. Ultimately, electroporated embryos fail to produce the full complement of post-mitotic motor neurons. Our findings indicate that GDE6 overexpression significantly affects radial glia function and positions GDE6 as a complementary factor to GDE2 during neurogenesis.

Effect of prior immunisation with smallpox vaccine for protection against human Mpox: A systematic review.

Monkeypox is an emerging threat to humans since a new outbreak in May 2022. It is hypothesised that increasing the immunologically naive population after the cessation of the smallpox vaccination campaign in the 1980s is one of the leading causes of it. A literature search was conducted using different electronic databases including MEDLINE (through PubMed), SCOPUS, Web of Science, Cochrane library, and EMBASE for relevant studies. After duplication removal, abstract and title screening, and full-text screening were done, the data were extracted, tabulated, and analysed. The risk of bias was assessed following the Risk of Bias Assessment tool for Non-randomised Studies. We found a total of 1068 relevant articles and finally, we included 6 articles including 2083 participants. The studies suggested that smallpox is 80.7% efficacious to prevent human monkeypox and the immunity provided by prior smallpox vaccination is long-lasting. Moreover, the smallpox vaccination decreases the risk of human monkeypox by 5.2-folds. Two cross-sectional studies based on the Democratic Republic of the Congo (DRC) including a total of around 1800 monkeypox cases found that unvaccinated participants had 2.73 and 9.64-fold increased risk of monkeypox compared to the vaccinated participants. Other studies in USA and Spain also demonstrated that unvaccinated people were more prone to develop monkeypox than vaccinated people. Furthermore, monkeypox incidence has increased by 20 folds, 30 years after the cessation of the smallpox vaccination campaign in DRC. Evidence-based preventive and therapeutic agents are still not available for human monkeypox. Further study should be done to explore the role of the smallpox vaccine in preventing human monkeypox.

The influence of apoE-deficiency and LDL-receptor-deficiency on the HDL subpopulation profile in mice and in humans.

OBJECTIVE: As apoE(-/-) and LDL-Receptor(-/-) mice are commonly used in atherosclerosis research; our objective was to point out the differences in HDL metabolism between mice and humans regarding the roles of apoE and LDLR. METHODS: We examined HDL particles obtained from wild type (WT), LDLR(-/-), and apoE(-/-) mice, as well as from normal, homozygous familial hypercholesterolemic (FH), and apoE-deficient human subjects by 2-dimensional non-denaturing PAGE followed by immunoblot and image analysis. RESULTS: In WT mice, the majority of apoA-I was in large (9.0-12.0 nm), α-mobility HDL with trace amounts of apoA-I in small, preß-1 HDL. In LDL(-/-) mice, both apoA-I- and apoE-containing HDL looked normal. About one-third of apoE was associated with large apoA-I-containing HDL (LpA-I:E) and two-thirds formed large HDL without apoA-I (LpE). In apoE(-/-) mice, apoA-I was detected in multiple, ß-preß-mobility, tightly-packed bands (7.0-13.0 nm) indicating that apoA-I in these animals was present only in poorly-lipidated, discoidal particles. Neither FH nor apoE-deficient humans showed significant alterations in apoA-I-containing HDL particles as compared to non-carriers. CONCLUSIONS: Our data indicate that apoE is necessary for the formation of spherical, lipidated HDL particles in mice, but not in humans, probably because mice lack CETP. Based on our data, we hypothesize that apoE(-/-) mice have little or no functional HDL, therefore results from apoE(-/-) mice cannot be extrapolated to humans without taking this significant difference into consideration.

Appropriateness use criteria for transthoracic echocardiography: relationship with radiology benefit managers preauthorization determination and comparison of the new (2010) criteria to the original (2007) criteria.

BACKGROUND: In response to growth in cardiac imaging, medical societies have published appropriateness use criteria (AUC) and payers have introduced preauthorization mandates, largely through radiology benefits managers (RBM). The correlation of algorithms used to determine preauthorization with the AUC is unknown. In addition, studies applying the 2007 AUC for transthoracic echocardiography revealed that many echocardiograms could not be classified. We sought to examine the impact of the revised 2010 AUC on appropriateness ratings of transthoracic echocardiograms previously classified by the 2007 AUC and the relationship of preauthorization determination to AUC rating. METHODS: We reclassified indications for transthoracic echocardiography as appropriate, inappropriate, uncertain, or unclassifiable using the 2010 AUC in the same 625 patients previously reported using 2007 AUC. We also evaluated the relationship between preauthorization status by 2 RBM precertification algorithms and appropriateness rating by 2007 AUC. RESULTS: The appropriateness classification of 148 (24%) transthoracic echocardiograms was changed by the updated AUC (P < .001). The number of unclassifiable echocardiograms was markedly reduced from 99 (16%) to 8 (1%), and more echocardiograms were classified as inappropriate (95 [15%] vs 45 [7%]) or uncertain (43 [7%] vs 0 [0%]). Limited correlation between the 2007 AUC rating and RBM preauthorization determinations was noted, with only moderate agreement with RBM no. 1 (90%, κ = 0.480, P < .001) and poor agreement with RBM no. 2 (72%, κ = 0.177, P < .001). CONCLUSION: The updated AUC (2010) provide enhanced clinical value compared with 2007 AUC. There is limited agreement between RBM preauthorization determination and 2007 AUC rating.

Adherence to appropriateness criteria for transthoracic echocardiography: comparisons between a regional department of Veterans Affairs health care system and academic practice and between physicians and mid-level providers.

We compared adherence to appropriateness criteria for transthoracic echocardiography in a Veterans Administration Medical Center (VAMC) and an academic practice and, within the VAMC, between physicians and mid-level providers. We reviewed 201 outpatient echocardiograms performed in the laboratory of an academic practice and 424 outpatient and inpatient studies performed at a VAMC. Echocardiographic examinations requested for indications addressed in the criteria were considered classified, and those for indications not addressed were considered unclassified. Classified studies were further rated as appropriate or inappropriate. Of 625 echocardiograms reviewed, 99 (16%) were unclassified. Approximately 80% of the indications for these could be assigned to 4 categories. Of the remaining 526 echocardiograms, indications were appropriate in 481 (91.4%) and inappropriate in 45 (8.6%). Among classified outpatient studies at the VAMC, mid-level providers requested significantly more studies for inappropriate indications than physicians (16.0% vs 7%, P = .024). There was no significant difference in the frequency of outpatient studies requested for inappropriate indications by VAMC and academic practice physicians (7.0% vs 9.5%, P = .558). The appropriateness criteria perform reasonably well at evaluating variations in use of echocardiography between health care systems and providers. The large majority of studies are requested for appropriate indications, although there is room for improvement.