Perimortem changes in clinical parameters in patients undergoing maintenance hemodialysis

Background End-of-life medical care for patients receiving maintenance hemodialysis (HD) therapy has become an increasingly important issue worldwide. Thus far, no clear indicators and/or biomarkers exist regarding the timing of HD therapy withdrawal. Methods To clarify the perimortem circumstances, we examined temporal changes in multiple clinical parameters during the last 10 serial HD sessions of 65 terminal patients with end-stage renal disease who had undergone maintenance HD and died in our hospital. Results The results showed that, while most of the laboratory data were unaltered, the physical parameters, such as systolic blood pressure and consciousness levels, gradually and significantly deteriorated toward the last HD session prior to death. The frequency of the use of vasopressors and O2 inhalation tended to increase. The accumulation of such severe conditions was observed at the last HD session. Of interest, the accumulation of severe conditions at the last HD session in patients with malignancies was significantly less than those with cardiovascular diseases or infectious diseases. The accumulation of severe conditions at the last HD session did not differ between patients who withdrew HD versus those who continued HD. Conclusion The results of the present study suggest that predicting the timing of maintenance HD therapy withdrawal is likely to be difficult and that the timing of maintenance HD therapy termination may differ among patient groups with distinct comorbid conditions.

Virus reactivation in a non-cirrhotic HBV patient requiring liver transplantation after cessation of nucleoside analogue therapy

Nucleos(t)ide analogues (NAs) are a mainstay of therapy for chronic hepatitis B (CHB) infections and have a profound effect on hepatitis B virus (HBV) suppression. We report a rare case of HBV reactivation in a CHB patient without cirrhosis following cessation of NA therapy that resulted in acute liver failure requiring liver transplantation. Investigation of the viral genetics and host immune responses suggest that viral mutations known to promote virus replication are associated with reactivation, whereas adaptive immunity to HBV remained defective in this patient. Viral sequencing may be useful for identifying mutations that are unfavorable for therapy withdrawal.

When and How Is it Possible to Stop Therapy in Patients with Lupus Nephritis?

Glucocorticoids and other immunosuppressants still represent the cornerstone drugs for the management of SLE (Systemic Lupus Erythematosus) and lupus nephritis. The refined use of these drugs over the years has allowed to obtain stable disease remission and improvement of the long-term kidney and patient survival. Nevertheless, a prolonged use of immunosuppressive agents may be accompanied by severe and even life-threatening side effects. Theoretically, a transient or even definitive withdrawal of immunosuppression could be useful to prevent iatrogenic morbidities. For many years, however, the risk of SLE reactivation has held clinicians back from trying to interrupt therapy. In this review we report the results of the attempts to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. The available data suggest that the therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy. A slow and gradual reduction of treatment under medical surveillance is needed to prevent flares of activity. After therapy withdrawal around one quarter of patients may have kidney or systemic flares. However, most flares may respond to therapy if rapidly diagnosed. The other patients can enter stable remission even for 20 years or more. The use of antimalarials can help in maintaining the remission after the withdrawal of the immunosuppressive therapy. A repeated kidney biopsy could be of help in deciding to stop therapy, but given the few available data, it cannot be considered essential.

Fixed dose combination of olmesartan and amlodipine in patients with hypertension and abdominal obesity. Data of 3-month observation of efficacy and adherence to therapy

Funding Acknowledgements Type of funding sources: None. Background Essential hypertension (H), which is combined with abdominal obesity (AO), is characterized by the early formation of refractoriness to antihypertensive therapy. In this regard, it is urgent to search for the most effective therapy regimens, among which fixed combinations (FC) of drugs have recently attracted considerable interest. Purpose To study the efficacy of FC olmesartan (O) and amlodipine (F) and adherence to it in patients with H and AO. Methods. 60 patients with grade 2 H with AO of I-II degrees (36 men and 24 women aged 48 to 62 years) were examined using standard clinical, biochemical and instrumental methods. Before enrollment in the study, all patients received various non-FC two-component combinations of antihypertensive drugs, however, target blood pressure (BP) levels were not achieved by any patient. After inclusion in the study, all patients were transferred to FC O and A, which was prescribed once a day , taking into account BP levels in the following daily doses: 20/5 mg; 40/5 mg and 40/10 mg. The examination was carried out for 3 months with dose adjustments every 7-10 days. Results. The use of FC O and A made it possible to achieve the target BP level after 3 month of therapy in 72% of patients with H and AO. At the same time, high adherence to this therapy was also noted: 80% of patients continued to receive this therapy for 3 months. It was found that in order to achieve target BP levels, in 84% of patients it was necessary to use O and A in a daily dose of 40/10 mg, in 16% of patients -in a dose of 40/5 mg. The tested FC was characterized by a low incidence of side effects, the most frequent of which was leg edema (in 7% of patients) and good tolerability (therapy withdrawal rate was 3%). Conclusion. The established high antihypertensive efficacy and tolerability of FC O and A in patients with H and AO indicates the promise of its widespread use in this category of patients.

Two successful pregnancies in a woman with active acromegaly

Acromegaly is a rare systemic disease, predominantly caused by growth hormone (GH)-secreting pituitary adenoma, leading to insulin-like growth factor-1 (IGF-1) overproduction. Pituitary adenoma extension and/or its treatment can cause infertility or subfertility in both sexes in different mechanisms. Pregnancies in women with active acromegaly are rarely observed but considered generally safe. Growth hormone and IGF-1 concentrations are usually stable during pregnancy and in most cases no significant tumour expansion emerges despite pharmacological therapy withdrawal. A 28 year-old woman with symptoms of acromegaly and amenorrhoea was admitted to the Department of Endocrinology. Diagnosis of acromegaly was made and treatment with somatostatin analogues (SSA) was initiated with subsequent surgical intervention. However, persistent acromegaly was diagnosed post-operatively due to residual tumour and the medical treatment was restarted. During follow-up the patient became pregnant twice and then treatment with somatostatin analogues was ceased. Both pregnancies were complicated by gestational diabetes and in the course of the second pregnancy treatment with dopamine agonist (DA) was commenced to alleviate persistent headaches and it was followed by clinical and biochemical improvement. The patient successfully delivered two healthy babies. After second labour treatment with SSA was resumed and the patient has achieved adequate disease control. The risk of pregnancy complications in women with acromegaly is slightly higher than in general population, especially if uncontrolled disease was present before conception or acromegaly was diagnosed during pregnancy. In rare cases pituitary tumour expansion during pregnancy occurs and then pharmacological or surgical interventions should be considered.

COVID-19 Pneumonia in Patients with Chronic Myocarditis (HBV-Associated with InfarctLike Debute): Specifics of the Diseases Course, the Role of the Basic Therapy (Part II)

Chronic infectious-immune myocarditis of severe course can potentially be considered as a factor that aggravates the course of new coronavirus disease (COVID-19) and increases the risk of adverse outcomes. The interaction of chronic myocarditis and COVID-19 during long-term immunosuppressive therapy has not been studied. We present a description of a 35-year-old female patient with chronic infectious-immune myocarditis (morphologically confirmed, with a history of infarction-like onset and thromboembolic complications), who had continuous immunosuppressive therapy with methylprednisolone and mycophenolate mofetil. The patient also received new oral anticoagulants and tenofovir (for chronic HBV infection). COVID-19 (SARS-Cov-2 RNA+) was diagnosed in May 2020. Risk factors for the adverse course of coronavirus infection included severe obesity, heart failure, and life-threatening ventricular arrhythmias. Correction of immunosuppressive therapy (withdrawal of the cytostatic agent, administration of hydroxychloroquine) and therapy with levofloxacin, an interleukin-17 inhibitor (netakimab) were performed. The severity of pneumonia and respiratory failure was moderate despite high fever and high levels of inflammatory markers in the blood (including interleukin-6). Signs of exacerbation of myocarditis, increased levels of troponin T and anticardial antibodies (compared with the initial ones) were not found. It can be assumed that supportive immunosuppressive therapy for myocarditis has a positive effect on the course of coronavirus pneumonia and avoids exacerbation of myocarditis. Careful continuation of immunosuppressive therapy with temporary withdrawal of aggressive cytostatics can be recommended in chronic myocarditis. Further study of the features of the course of previous myocarditis and COVID-19 pneumonia is necessary.

Heart rate as a marker of relapse during withdrawal of heart failure therapy in patients with recovered dilated cardiomyopathy: an analysis from TRED-HF

Introduction In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short-term during phased withdrawal of drug therapy. Non-invasive markers of relapse may be used to monitor patients who wish a trial of therapy withdrawal and provide insights into the pathophysiological drivers of relapse. Purpose To investigate the relationship between changes in heart rate (HR) and relapse amongst patients with recovered DCM undergoing therapy withdrawal in TRED-HF. Methods Patients with recovered DCM were randomised to phased withdrawal of therapy or to continue therapy for 6 months. After 6 months of continued therapy, those in the control arm underwent withdrawal of therapy in a single arm crossover phase. HR was measured at each study visit. Mean HR and 95% confidence intervals (CI) were calculated at baseline, 45 days after baseline, 45 days prior to the end of the study or relapse and at the end of the study or relapse. Patients were stratified by treatment arm and the occurrence of the primary relapse end-point. Heart rate at follow-up was compared amongst patients who had therapy withdrawn and relapsed versus those who had therapy withdrawn and did not. ANCOVA was used to adjust for differences in HR at baseline between the two groups. Results Of 51 patients randomised, 26 were assigned to continue therapy and 25 to withdraw therapy. In the randomised and cross-over phases, 20 patients met the primary relapse end-point; one patient withdrew from the study and one patient completed follow-up in the control arm but did not enter the cross-over phase. Mean HR (standard deviation) at baseline and follow-up for (i) patients in the control arm was 69.9 (9.8) & 65.9 (9.1) respectively; (ii) for those who had therapy withdrawn and did not relapse was 64.6 (10.7) & 74.7 (10.4) respectively; and (iii) for those who had therapy withdrawn and relapsed was 68.3 (11.3) & 86.1 (11.8) respectively [all beats per minute]. The mean change in HR between the penultimate visit and the final visit for those who had therapy withdrawn and did not relapse was −2.4 (9.7) compared to 3.1 (15.5) for those who relapsed. After adjusting for differences in HR at baseline, the mean difference in HR measured at follow-up between patients who underwent therapy withdrawal and did, and did not relapse was 10.4bpm (95% CI 4.0–16.8; p=0.002) (Figure 1 & Table 1). Conclusion(s) A larger increase in HR may be a simple and effective marker of relapse for patients with recovered DCM who have insisted on a trial of therapy withdrawal. Whether HR control is crucial to the maintenance of remission amongst patients with improved cardiac function, or is simply a marker of deteriorating cardiac function, warrants further investigation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation