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Favorable response to multimodal treatment in hepatocellular carcinoma with inferior vena cava and right atrial tumor thrombus and left adrenal gland metastasis: A case report and literature review.
Sun, N, Zhang, J, Li, B, Li, A, Lv, M, Zhang, C
Medicine. 2021;(49):e27987
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Abstract
RATIONALE Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths and the sixth most commonly diagnosed cancer globally. Interdisciplinary and multimodal treatment strategies are essential for a successful therapy in HCC. Established therapies for HCC treatment include surgical resection, liver transplantation, local ablative therapies, transarterial chemoembolization (TACE), tyrosine kinase inhibitors (TKIs), immunotherapy, and radiotherapy (RT). PATIENT CONCERNS A 52-year-old male patient did an ultrasound scan and found a large mass within the right lobe of the liver and gallstones in December 2018. He had a history of chronic hepatitis C virus infection (30 years) and was treated with sofosbuvir (400 mg, q.d.) for 1 year. The patient never had any symptoms of gallstones. Enhanced abdominal computed tomography of this patient showed a heterogeneous irregular mass with the largest measurement of up to 13.7 × 11.1 cm in size in the right lobe of the liver, meanwhile also had inferior vena cava (IVC) tumor thrombus, right atrial (RA) tumor thrombus, and left adrenal gland metastasis. The laboratory test data revealed that the serum tumor marker α-fetoprotein was 2.63 ng/mL, cancer antigen 19-9 (CA 19-9) was 34.40 U/mL, and protein induced by Vitamin K absence was 391.94 mAU/mL. DIAGNOSIS HCC with IVC tumor thrombus, RA tumor thrombus, and left adrenal gland metastasis, and gallstones. INTERVENTIONS He was hospitalized and received TACE treatment, oral TKIs, intravenous drip programmed cell death-1 (PD-1) inhibitor and RT. OUTCOMES The patient showed a favorable response after consecutive treatment with TACE, TKIs, PD-1 inhibitor, and RT. Until now, the patient has survived 34 months since the diagnosis of the disease. LESSONS Our case suggests that TACE combined with TKIs, PD-1 inhibitor, and RT may be a suitable treatment option for advanced HCC patients with IVC tumor thrombus and/or RA tumor thrombus, and/or adrenal gland metastasis.
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Treatment of portal vein thrombosis: an updated narrative review.
Caiano, LM, Riva, N, Carrier, M, Gatt, A, Ageno, W
Minerva medica. 2021;(6):713-725
Abstract
Portal vein thrombosis (PVT) is the most frequent among the splanchnic vein thrombosis, accounting for 90% of cases. More than half of PVT are provoked by liver cirrhosis, solid cancer or myeloproliferative neoplasms. The remaining cases are non-malignant non-cirrhotic PVT and include either unprovoked events or thrombosis secondary to other less common risk factors (e.g. abdominal surgery, intrabdominal inflammations/infections, or hormonal stimuli). Anticoagulant therapy in patients with acute symptomatic PVT should be started early after diagnosis, if no active bleeding, to obtain greater vessel recanalization and reduce the occurrence of portal-hypertension related complications. Gastroesophageal varices do not represent a contraindication to anticoagulant treatment, as long as adequate measures have been undertaken for the prophylaxis of gastroesophageal bleeding. Different treatment options (unfractionated or low molecular weight heparin, vitamin K antagonists and direct oral anticoagulants [DOACs]) can be considered. In this narrative review we will discuss the treatment of PVT in the three most common scenarios (cirrhosis-associated, cancer-associated and non-malignant non-cirrhotic PVT). We will also discuss the role of the DOACs and summarize recent guidelines on this topic.
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[Modern treatment of deep vein thrombosis and pulmonary embolism].
Renczes, J, Lindhoff-Last, E
Der Internist. 2019;(6):644-655
Abstract
Virchow's triad has been known for a 100 years. The development of therapeutic possibilities during this time was enormous. Today anticoagulant therapy is much more differentiated. Four new oral substances have replaced the traditional treatment with vitamin K antagonists in angiology. A standardized dosage is available. The monitoring of the coagulation parameters is no longer necessary, but it is important to monitor renal function. Direct oral anticoagulants are approved for the treatment of venous thrombosis and pulmonary embolism, but not during pregnancy or in children. Severe bleeding complications, especially intracerebral bleeding, are less common. The incidence of venous thromboembolism is still high. Obesity and cancer are of particular importance. The "therapeutic pact" with the patient requires that physicians master the art of "talking medicine".
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Deep vein thrombosis during long-term surveillance of patients with liver transplantation.
Balaceanu, A
Irish journal of medical science. 2019;(4):1191-1193
Abstract
BACKGROUND In the European Liver Transplant Registry, there are 137,863 liver transplantations recorded. Forty-one percent of patients survived 20 years after liver transplantation in the European countries. From 1988, when the US database for liver transplantation was created, to 2006, there are more than 56,000 liver transplants. Almost 80% of the liver transplant recipients survived 5 years after transplantation. The incidence of deep vein thrombosis (DVT) in the European population is 70-140/100.000 person-years. Cancer, paresis, immobilization, thrombophilia, inflammatory bowel disease, replacement hormonal or contraceptive therapies are associated with an increased risk of occurrence DVT or complications. The incidence of DVT in long-term surveillance of liver transplant recipients is unknown. Immunosuppressive therapy, thrombophilia abnormalities, hepatitis C and hepatocellular carcinoma recurrence, renal insufficiency, malignant tumours, obesity and diabetes were associated with DVT in long-term post-liver transplantation. The reported maximum time between liver transplantation and DVT was 210 days. AIM: The aim of the study is to update existing data in the literature regarding the occurrence and management of deep vein thrombosis in liver transplant patients over the long-term surveillence period. CONCLUSIONS There are no specific guideline recommendations regarding acute DVT treatment in long-term surveillance after liver transplantation. Low molecular weight heparin (LMWH), unfractionated heparin (UFH) and vitamin K antagonist (VKA) are the anticoagulants used in specific complications post-transplantation. The safety and the efficacy of direct anticoagulants in liver transplantation recipients need to be assessed in future trials. Given that long-term survival of liver transplantation is much improved, complications associated with transplantation and ageing require appropriate cardiovascular guidelines.
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5.
Apixaban-induced subdural bleeding: case presentation and literature review.
Alayad, E, Khairy, S, Aloraidi, A
BMJ case reports. 2018
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Abstract
Apixaban is a factor Xa inhibitor which is a non-vitamin K dependent oral anticoagulant known tocause the lowest rate of intracranial bleeding among the same kind of inibitors. In this paper, we report a rare case in a 60-year-old man with a history of hypertension and oligodendroglioma on apixaban for deep venous thrombosis who presented to our hospital with decreased level of consciousness and slurred speech with rapid deterioration. We highlight the risk of subdural bleeding requiring immediate neurosurgical intervention due to apixaban, with literature review.
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Heparin promotes recanalization of venous thrombotic occlusions.
Poredos, P, Poredos, P, Jezovnik, MK
International angiology : a journal of the International Union of Angiology. 2018;(4):261-268
Abstract
Thrombosis is a consequence of disbalance between the procoagulant and fibrinolytic activity of blood and is frequently associated with chronic sequelae, which are the consequence of chronic occlusion of affected veins. Treatment of venous thrombosis should not be oriented in the prevention of thrombus progression and associated thromboembolic events, but also in stimulation of thrombolysis and recanalization of occluded veins, which are one of the most important preventive mechanisms of late sequelae, including post-thrombotic syndrome. The treatment of acute venous thrombosis (superficial and deep) is based on drugs with anticoagulant activity, like antagonists of vitamin K, heparins, and new oral anticoagulants. One of the most frequently used anticoagulant drugs is heparin, particularly the low molecular weight heparin (LMWH). It was shown that besides strong anticoagulant activity heparin has pro-fibrinolytic effects, which promote thrombolysis and recanalization of occluded veins. LMWH markedly increases tissue factor pathway inhibitor levels and a release of tissue plasminogen activator from vascular endothelium. Heparins are also capable of increasing the nitrogen oxide level, which is responsible for circulatory homeostasis.
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Developments of Anticoagulants and New Agents with Anti-Coagulant Effects in Deep Vein Thrombosis.
Dang, YP, Chen, YF, Li, YQ, Zhao, L
Mini reviews in medicinal chemistry. 2017;(4):338-350
Abstract
Deep Vein Thrombosis (DVT) has been known as a common medical problem all over the world. Thrombus traveling in blood vessels may lead to pulmonary embolism (PE), associated with high rates of mortality. Anticoagulant therapy is the mainstay treatment of DVT. Common anticoagulants, Vitamin K antagonists (VKAs), unfractionated heparin (UFH) and Low-molecular-weight heparin (LMWH) have been used in clinical application over decades, but can increase the risk of hemorrhage. Thereby, several new oral anticoagulants (NOACs) have been developed, which includes direct thrombin inhibitors (DTI) and direct factor Xa inhibitors. To be contrast with VKAs and UFH, NOACs have many advantages such as rapid offset action, few drug/food interactions and no need for routine coagulation monitoring, etc. Many NOACs are still being evaluated in Phase III clinical trials such as Betrixaban and Darexaban (YM150). However, NOACs still have problems to be solved such as lack of antidotes and laboratory monitoring, high drug costs, etc. Besides, several agents have already shown the potential to be new anticoagulants. Factor Xa play an important role in thrombin generation and coagulation pathway. Thus, the new compounds directly targeting on factor Xa for prevention DVT are highly anticipated. DPC423, a new series of 6-substituted coumarin derivatives and Phenyltriazolinones as potent factor Xa inhibitors have been recently reported. Recent studies revealed that agents extracted from botanicals not only have anti-coagulant effects but also possess other pharmacological activities such as anti-inflammation to alleviate the post-thrombotic syndromes. All the evidence above suggests that many new compounds might have great potential to be more effective and safe oral anticoagulants.
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Platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis.
Colli, A, Gana, JC, Yap, J, Adams-Webber, T, Rashkovan, N, Ling, SC, Casazza, G
The Cochrane database of systematic reviews. 2017;(4):CD008759
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Abstract
BACKGROUND Current guidelines recommend screening of people with oesophageal varices via oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis. This requires that people repeatedly undergo unpleasant invasive procedures with their attendant risks, although half of these people have no identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis. Platelet count, spleen length, and platelet count-to-spleen length ratio are non-invasive tests proposed as triage tests for the diagnosis of oesophageal varices. OBJECTIVES Primary objectives To determine the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices of any size in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology. To investigate the accuracy of these non-invasive tests as triage or replacement of oesophago-gastro-duodenoscopy. Secondary objectives To compare the diagnostic accuracy of these same tests for the diagnosis of high-risk oesophageal varices in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology.We aimed to perform pair-wise comparisons between the three index tests, while considering predefined cut-off values.We investigated sources of heterogeneity. SEARCH METHODS The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), and Science Citation Index - Expanded (Web of Science) (14 June 2016). We applied no language or document-type restrictions. SELECTION CRITERIA Studies evaluating the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices via oesophago-gastro-duodenoscopy as the reference standard in children or adults of any age with chronic liver disease or portal vein thrombosis, who did not have variceal bleeding. DATA COLLECTION AND ANALYSIS Standard Cochrane methods as outlined in the Cochrane Handbook for Diagnostic Test of Accuracy Reviews. MAIN RESULTS We included 71 studies, 67 of which enrolled only adults and four only children. All included studies were cross-sectional and were undertaken at a tertiary care centre. Eight studies reported study results in abstracts or letters. We considered all but one of the included studies to be at high risk of bias. We had major concerns about defining the cut-off value for the three index tests; most included studies derived the best cut-off values a posteriori, thus overestimating accuracy; 16 studies were designed to validate the 909 (n/mm3)/mm cut-off value for platelet count-to-spleen length ratio. Enrolment of participants was not consecutive in six studies and was unclear in 31 studies. Thirty-four studies assessed enrolment consecutively. Eleven studies excluded some included participants from the analyses, and in only one study, the time interval between index tests and the reference standard was longer than three months. Diagnosis of varices of any size. Platelet count showed sensitivity of 0.71 (95% confidence interval (CI) 0.63 to 0.77) and specificity of 0.80 (95% CI 0.69 to 0.88) (cut-off value of around 150,000/mm3 from 140,000 to 150,000/mm3; 10 studies, 2054 participants). When examining potential sources of heterogeneity, we found that of all predefined factors, only aetiology had a role: studies including participants with chronic hepatitis C reported different results when compared with studies including participants with mixed aetiologies (P = 0.036). Spleen length showed sensitivity of 0.85 (95% CI 0.75 to 0.91) and specificity of 0.54 (95% CI 0.46 to 0.62) (cut-off values of around 110 mm, from 110 to 112.5 mm; 13 studies, 1489 participants). Summary estimates for detection of varices of any size showed sensitivity of 0.93 (95% CI 0.83 to 0.97) and specificity of 0.84 (95% CI 0.75 to 0.91) in 17 studies, and 2637 participants had a cut-off value for platelet count-to-spleen length ratio of 909 (n/mm3)/mm. We found no effect of predefined sources of heterogeneity. An overall indirect comparison of the HSROCs of the three index tests showed that platelet count-to-spleen length ratio was the most accurate index test when compared with platelet count (P < 0.001) and spleen length (P < 0.001). Diagnosis of varices at high risk of bleeding. Platelet count showed sensitivity of 0.80 (95% CI 0.73 to 0.85) and specificity of 0.68 (95% CI 0.57 to 0.77) (cut-off value of around 150,000/mm3 from 140,000 to 160,000/mm3; seven studies, 1671 participants). For spleen length, we obtained only a summary ROC curve as we found no common cut-off between studies (six studies, 883 participants). Platelet count-to-spleen length ratio showed sensitivity of 0.85 (95% CI 0.72 to 0.93) and specificity of 0.66 (95% CI 0.52 to 0.77) (cut-off value of around 909 (n/mm3)/mm; from 897 to 921 (n/mm3)/mm; seven studies, 642 participants). An overall indirect comparison of the HSROCs of the three index tests showed that platelet count-to-spleen length ratio was the most accurate index test when compared with platelet count (P = 0.003) and spleen length (P < 0.001). DIagnosis of varices of any size in children. We found four studies including 277 children with different liver diseases and or portal vein thrombosis. Platelet count showed sensitivity of 0.71 (95% CI 0.60 to 0.80) and specificity of 0.83 (95% CI 0.70 to 0.91) (cut-off value of around 115,000/mm3; four studies, 277 participants). Platelet count-to-spleen length z-score ratio showed sensitivity of 0.74 (95% CI 0.65 to 0.81) and specificity of 0.64 (95% CI 0.36 to 0.84) (cut-off value of 25; two studies, 197 participants). AUTHORS' CONCLUSIONS Platelet count-to-spleen length ratio could be used to stratify the risk of oesophageal varices. This test can be used as a triage test before endoscopy, thus ruling out adults without varices. In the case of a ratio > 909 (n/mm3)/mm, the presence of oesophageal varices of any size can be excluded and only 7% of adults with varices of any size would be missed, allowing investigators to spare the number of oesophago-gastro-duodenoscopy examinations. This test is not accurate enough for identification of oesophageal varices at high risk of bleeding that require primary prophylaxis. Future studies should assess the diagnostic accuracy of this test in specific subgroups of patients, as well as its ability to predict variceal bleeding. New non-invasive tests should be examined.
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Pentasaccharides for the treatment of deep vein thrombosis.
Brandao, GM, Junqueira, DR, Rollo, HA, Sobreira, ML
The Cochrane database of systematic reviews. 2017;(12):CD011782
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Abstract
BACKGROUND Standard treatment of deep vein thrombosis (DVT) is based on antithrombotic therapy, initially with parenteral administration of unfractionated heparin or low molecular weight heparins (LMWH) for five to seven days, then subsequent long-term therapy with oral vitamin K antagonists (e.g. warfarin). Pentasaccharides are novel anticoagulants that may be favourable over standard therapy due to their predictable effect, no need for frequent monitoring or re-dosing, and few known drug interactions. Heparin-induced thrombocytopenia, a harmful effect of heparins, appears to be rare during treatment with pentasaccharides. OBJECTIVES To assess the efficacy and harms of pentasaccharides for the treatment of deep vein thrombosis. SEARCH METHODS The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (22 March 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2) (searched 22 March 2017). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles for additional citations. SELECTION CRITERIA We included randomised controlled trials in which people 18 years of age or older with a DVT confirmed by standard imaging techniques were allocated to receive a pentasaccharide (fondaparinux, idraparinux, or idrabiotaparinux) for the treatment of DVT in comparison with standard therapy or other treatments. DATA COLLECTION AND ANALYSIS We extracted data characterising the included trials according to the methods, participants, interventions, and outcomes. We assessed risk of bias using Cochrane's 'Risk of bias' tool and employed the GRADE methodology to evaluate the quality of the evidence.The main primary outcome for efficacy was recurrent venous thromboembolism (VTE), and the main primary outcome for harm was major and clinically relevant bleeding. Since our outcomes were dichotomous, we calculated the risk ratio (RR) with a 95% confidence interval (CI). We combined the effects of different comparisons through a meta-analysis using a fixed-effect model. MAIN RESULTS We included five randomised controlled trials of 6981 participants comparing pentasaccharides with standard therapy or other pentasaccharides. The quality of the evidence varied depending on the outcome and was judged as of moderate to very low quality. We downgraded the quality of the evidence due to risk of bias or imprecision, or both.Two studies evaluated fondaparinux, at doses of 5.0 mg, 7.5 mg, and 10.0 mg, plus vitamin K antagonist in comparison with standard therapy. A meta-analysis of these two studies showed no clear difference in the risk of recurrent VTE (RR 0.80, 95% CI 0.43 to 1.47; 2658 participants); moderate-quality evidence. The frequencies of major bleeding were similar between interventions in the initial period of treatment (approximately five days) (RR 1.15, 95% CI 0.39 to 3.44; 2645 participants) and at three months' follow-up (RR 1.05, 95% CI 0.64 to 1.71; 2645 participants). We judged the quality of the evidence as moderate.One study (757 participants) compared idrabiotaparinux (3.0 mg) with idraparinux (2.5 mg) and demonstrated no clear difference in the risk of recurrent VTE at six months' follow-up (RR 0.72, 95% CI 0.31 to 1.69); low-quality evidence. Major bleeding during the initial treatment period was not reported. Major bleeding at six-month follow-up was less frequent in participants receiving idrabiotaparinux versus participants treated with idraparinux (RR 0.21, 95% CI 0.06 to 0.71); low-quality evidence.The effect of an initial treatment with LMWH followed by three months of idraparinux (10 mg) showed no clear difference from standard therapy for risk of recurrent VTE (RR 1.51, 95% CI 0.26 to 8.90; 263 participants); very low-quality evidence; one study. Major bleeding during the initial treatment period was not reported. The frequency of major and other clinically relevant bleeding at three months' follow-up ranged from 2% to 15% in participants receiving LMWH and increasing doses of idraparinux of 2.5 mg, 5 mg, 7.5 mg, or 10 mg. When dosage groups were combined, there was no clear difference in major plus other clinically relevant bleeding or in major bleeding alone between the idraparinux treatment group and the standard therapy group (RR 1.30, 95% CI 0.70 to 2.40; 659 participants; RR 3.76, 95% CI 0.50 to 28.19; 659 participants, respectively); very low-quality evidence.One study (2904 participants) compared idraparinux (2.5 mg) to standard therapy. There was no clear difference in the risk of recurrent VTE at three months' follow-up (RR 0.98, 95% CI 0.64 to 1.48); low-quality evidence. Major bleeding during the initial treatment period was not reported. Major bleeding at three months of follow-up appeared to be similar in the idraparinux group and the standard therapy group (RR 0.71, 95% CI 0.34 to 1.47); very low-quality evidence. AUTHORS' CONCLUSIONS We found moderate-quality evidence that the effects of fondaparinux at doses of 5.0 mg, 7.5 mg, and 10.0 mg plus vitamin K antagonist are similar in terms of recurrent VTE and risk of major bleeding compared with standard treatment for DVT.Low-quality evidence suggests equal efficacy of idraparinux at 2.5 mg and the equimolar dose of 3.0 mg of idrabiotaparinux with regard to recurrent VTE, but a higher frequency of major bleeding was observed in participants treated with idraparinux.We judged evidence on the effectiveness of idraparinux compared with standard therapy, with or without initial treatment with LMWH, and on associated bleeding risk to be low to very low quality, therefore we have very limited confidence in the estimated effects.The observed similar effectiveness in terms of recurrent DVT and harmful effects in terms of bleeding risk with fondaparinux plus vitamin K antagonist compared to standard treatment for DVT suggest that it may be an alternative to conventional anticoagulants for the treatment of DVT in certain circumstances.
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Management of Venous Thromboembolism: Recent Advances in Oral Anticoagulation Therapy.
Finks, SW, Trujillo, TC, Dobesh, PP
The Annals of pharmacotherapy. 2016;(6):486-501
Abstract
OBJECTIVE To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products. DATA SOURCES Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information. STUDY SELECTION AND DATA EXTRACTION Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions. DATA SYNTHESIS The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy. CONCLUSIONS The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.