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European Journal of Internal Medicine Nov 2023Diabetic ketoacidosis (DKA) is an acute life-threatening emergency in patients with diabetes, it can result in serious morbidity and mortality. Management of DKA... (Review)
Review
Diabetic ketoacidosis (DKA) is an acute life-threatening emergency in patients with diabetes, it can result in serious morbidity and mortality. Management of DKA requires reversing metabolic derangements, correcting volume depletion, electrolyte imbalances and acidosis while concurrently treating the precipitating illness. There are still controversies regarding certain aspects of DKA management. Different society guidelines have inconsistencies in their recommendations, while some aspects of treatment are not precise enough or have not been thoroughly studied. These controversies may include issues such as optimal fluid resuscitation, rate and type of Insulin therapy, potassium and bicarbonate replacement. Many institutions follow common society guidelines, however, other institutions either develop their own protocols for internal use or do not routinely use any protocols, resulting in inconsistencies in treatment and increased risk of complications and suboptimal outcomes. The objectives of this article are to review knowledge gaps and controversies in the treatment of DKA and provide our perspective on these issues. Moreover, we believe that special patient factors and comorbidities should receive more careful attention and consideration. Factors like pregnancy, renal disease, congestive heart failure, acute coronary syndrome, older age, use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and site of care all impact the treatment approach and require tailored management strategies. However, guidelines often lack sufficient recommendations regarding specific conditions and comorbidities, we aim to address unique circumstances and provide an approach to managing complex patients with specific conditions and co-morbidities. We also sought to examine changes and trends in the treatment of DKA, illuminate on aspects of latest research with a perspective towards future developments and modifications.
Topics: Pregnancy; Female; Humans; Diabetic Ketoacidosis; Insulin; Fluid Therapy; Potassium; Diabetes Mellitus
PubMed: 37419787
DOI: 10.1016/j.ejim.2023.07.005 -
Clinical Implant Dentistry and Related... Aug 2023Peri-implant mucosal integration is becoming a critical aspect for long term implant health and can be triggered the selection of implant components. The aim of this... (Review)
Review
Peri-implant mucosal integration is becoming a critical aspect for long term implant health and can be triggered the selection of implant components. The aim of this review is therefore to investigate the evidence concerning implant connection and abutment characteristics (abutment materials, design, handling) as predisposing or precipitating factor for peri-implant mucositis and peri-implantitis. Although the evidence that these features can directly predispose/precipitate peri-implant diseases is limited, there are -few- studies showing a potential role of the implant connection, trans-mucosal configuration, and handling in the development of early bone loss and/or peri-implantitis. With bone level implants, conical internal connections (with inherent platform switching) might be preferred over internal flat-flat and external connections to decrease the risk of early bone loss and potentially the risk of peri-implant disease. Moreover, there is a trend suggesting moving the prosthetic interface coronally (to the juxta-mucosal level) as soon as possible to reduce the number of disconnections and to limit the risk of cements remnants. This can be achieved by choosing a tissue-level implant or to place a trans-mucosal abutment (one abutment-one time approach) to optimize the peri-implant soft tissue seal. In absence of evidence for the biocompatibility regarding several restorative materials, biocompatible materials such as titanium or zirconia should be preferred in the trans-mucosal portion. Finally, higher implants (≥2mm) with an emergence angle below 30° seem more favourable. It should however be noted that some of this information is solely based on indirect information (such as early bone loss) and more research is needed before making firm recommendations about abutment choice. [Correction added on 13 March 2023, after first online publication: 'longer implants (≥2mm)' was changed to 'higher implants (≥2mm)' in this version.].
Topics: Humans; Peri-Implantitis; Dental Implants; Dental Implant-Abutment Design; Precipitating Factors; Dental Abutments
PubMed: 36825512
DOI: 10.1111/cid.13185 -
Diagnostics (Basel, Switzerland) Aug 2023Diabetic ketoacidosis (DKA) represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM)... (Review)
Review
Diabetic ketoacidosis (DKA) represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, Type 2 Diabetes Mellitus (T2DM) in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia, and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline and Scopus databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, between DKA and hyperosmolar hyperglycaemic state (HHS), and between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen, and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration, restoration of shifting electrolyte disorders and addressing underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention, and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.
PubMed: 37568965
DOI: 10.3390/diagnostics13152602 -
European Journal of Anaesthesiology Feb 2024Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role...
Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.
Topics: Adult; Humans; Emergence Delirium; Anesthesiology; Postoperative Complications; Delirium; Consensus; Critical Care; Risk Factors
PubMed: 37599617
DOI: 10.1097/EJA.0000000000001876 -
American Journal of Clinical Dermatology Jul 2023Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including... (Review)
Review
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.
Topics: Humans; Acute Generalized Exanthematous Pustulosis; Diagnosis, Differential; Skin; Exanthema; Erythema
PubMed: 37156992
DOI: 10.1007/s40257-023-00779-3 -
Cardiovascular Drugs and Therapy Aug 2023Antiphospholipid syndrome (APS) is a systemic autoimmune disorder clinically characterized by recurrent arterial and venous thrombosis and/or pregnancy morbidity in the... (Review)
Review
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder clinically characterized by recurrent arterial and venous thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. Currently, treatment is mainly focused on anticoagulation, but therapies targeting mechanisms involved in APS autoimmune pathogenesis could play an important role in specific settings. An evidence-based therapeutic approach is limited by the broad clinical spectrum of the syndrome and the nature of a "rare disease" that makes it difficult to carry out well-designed prospective studies. Vitamin K antagonists (AVK), notably warfarin, are the standard treatment for preventing recurrent venous thrombosis and perhaps also arterial thrombosis. Direct oral anticoagulants (DOACs) are not recommended at least in patients with triple positivity APS. Treatment options for the prevention of pregnancy complications in obstetric APS, as combined use of aspirin and heparin, low-dose prednisolone, hydroxychloroquine, intravenous immunoglobulin (IVIG), may improve pregnancy outcome. The catastrophic antiphospholipid syndrome (CAPS) is the most severe form of APS with acute multiple organ involvement and small vessel thrombosis. Glucocorticoids, heparin, plasma exchange or IVIG, rituximab, or eculizumab must be added to concurrent treatment of precipitating factors (e.g. infections) as rescue therapies. Finally, it has been observed that SARS COV2 infection may produce vascular complications mimicking the clinical and pathophysiological features of APS and particularly of CAPS. From this point of view, attention has been focused on the "protective" role of anticoagulant therapy in preventing thrombotic complication when these clinical conditions coexist.
PubMed: 37572208
DOI: 10.1007/s10557-023-07496-3 -
Nucleic Acids Research Sep 2023Histone deacetylase 6 (HDAC6) mediates DNA damage signaling by regulating the mismatch repair and nucleotide excision repair pathways. Whether HDAC6 also mediates DNA...
Histone deacetylase 6 (HDAC6) mediates DNA damage signaling by regulating the mismatch repair and nucleotide excision repair pathways. Whether HDAC6 also mediates DNA double-strand break (DSB) repair is unclear. Here, we report that HDAC6 negatively regulates DSB repair in an enzyme activity-independent manner. In unstressed cells, HDAC6 interacts with H2A/H2A.X to prevent its interaction with the E3 ligase RNF168. Upon sensing DSBs, RNF168 rapidly ubiquitinates HDAC6 at lysine 116, leading to HDAC6 proteasomal degradation and a restored interaction between RNF168 and H2A/H2A.X. H2A/H2A.X is ubiquitinated by RNF168, precipitating the recruitment of DSB repair factors (including 53BP1 and BRCA1) to chromatin and subsequent DNA repair. These findings reveal novel regulatory machinery based on an HDAC6-RNF168 axis that regulates the H2A/H2A.X ubiquitination status. Interfering with this axis might be leveraged to disrupt a key mechanism of cancer cell resistance to genotoxic damage and form a potential therapeutic strategy for cancer.
Topics: Humans; Cell Line, Tumor; DNA Damage; DNA Repair; Histone Deacetylase 6; Ubiquitin; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 37503842
DOI: 10.1093/nar/gkad631 -
Cephalalgia : An International Journal... Dec 2023Migraine's astonishing prevalence and preserved genetic background contrast with the definition of a disease and the biological meaning of experiencing recurrent, severe... (Review)
Review
INTRODUCTION
Migraine's astonishing prevalence and preserved genetic background contrast with the definition of a disease and the biological meaning of experiencing recurrent, severe headache attacks is still puzzling.
METHODS
To provide a comprehensive explanation of the migraine evolutionary meaning, we review (i) the putative role of the autonomic nervous system in migraine attacks, (ii) the inter-ictal autonomic, functional, and metabolic signature of migraine patients, (iii) the bio-behavioral perspective of pain, and (iv) the allostatic perception of migraine chronification.
RESULTS
Migraineurs have inter-ictal cortical hyperexcitability and metabolic dysfunction that predisposes to brain energetic imbalance. Multiple precipitating factors may lead to brain energy consumption over the migraine attack generation threshold. In response, the brain engenders adaptive, evolutionary conserved, autonomic-behavior responses through the antidromic activation of the trigeminovascular system. The sickness behavior and severe pain experienced during migraine attacks result in avoiding mental and physical activity, allowing brain energy restoration. Chronic exposure to stressors may result in an allostatic overload, leading to maladaptive chronic activation of these responses. In this bio-behavioral perspective, the chronification of migraine should be envisioned as a pathological process, whereas the migraine itself should not.
CONCLUSION
Migraine has an evolutionary (Darwinian) meaning.
Topics: Humans; Migraine Disorders; Brain; Pain; Autonomic Nervous System; Headache
PubMed: 38041827
DOI: 10.1177/03331024231209303