Palliative care terminology and practice in intensive care units in the Czech Republic: results of PEOpLE-C19 study

Study goal: Palliative care is an essential part of a complex approach to patients in the intensive care unit (ICU). This study aimed to describe palliative care practice in ICU in the Czech Republic. Study type: a cross-sectional, questionnaire study Material and methods: The inclusion criteria for study participation were nurses or physicians taking care of patients in the ICU for patients with Coronavirus Disease 2019 (COVID-19). The participants could participate by filling out the electronic survey with 40 questions. The questionnaire was evaluated by descriptive statistical analysis. Results: 313 questionnaires were analyzed. Participants reported up to 15 different terms for end-of-life care, the most often being palliative care (75.1%, n=235). The supportive care, especially sedatives, was most frequently adjusted according to the patient's needs. On the other hand, as a standard approach, the parenteral (35.8%, n=112) and enteral (17.3%, n=54) nutrition were most often withdrawn. Regarding organ support, renal replacement therapy (69.7%, n=218) and vasopressors (60.4%, n=189) were often withdrawn. The most rarely withdrawn organ support was artificial ventilation (24.6%, n=77), endotracheal intubation (11.5%,n=36), and tracheostomy cannula (2.9%, n=9). The majority of respondents would appreciate further education in palliative care. Conclusion: Palliative care is an essential theme not only in the COVID-19 pandemic. The palliative care terminology and practice used in the Czech Republic are heterogeneous. There is a space for further research and education in palliative care.

Ambroxol therapy for patients with Gaucher disease type 1, either poor responders to enzyme replacement therapy/substrate reduction therapy (ERT/SRT) or untreated

Ambroxol hydrochloride is an oral mucolytic drug, available over-the-counter for many years as cough medicine, which was found to also act as a pharmacological chaperone for mutant glucocerebrosidase, albeit in a several-fold higher dose. Proof-of-concept reports have been published over the past decade in all three forms of Gaucher disease (GD). The current study aimed to assess the safety and efficacy of 12-months ambroxol 600 mg/day in 3 groups of type 1 GD patients with sub-optimal response, after a minimum of 3 years, to enzyme replacement therapy (ERT)/substrate reduction therapy (SRT) defined as lumbar spine bone density <−2.0 t-score, or platelet count<100 × 10−3/L, or LysoGb1 > 200 ng/ml, and for a group of naïve patients, i.e., never treated or stopped therapy >12 months prior to enrollment, who had abnormal values in 2 of the 3 above-mentioned parameters. Forty patients were enrolled: 28 ERT/SRT treated and 12 naïve;21 (52%) males, mean age 52 years (range 24–84). Safety aspects included several adverse effects (mainly gastrointestinal, excessive saliva, and vertigo) all mild and transient in nature, but led to drug discontinuation in 14 patients, additional dropouts were 7 patients due to COVID19 pandemic and 3 due to personal reasons. Of the remaining 16 patients, 14 have completed 12 months, and 2 are ongoing. Of the 14 completers, 5 (~36%) achieved significant improvement in at least one of the three parameters, and nine did not demonstrate any improvement nor deterioration. The interpretation of the results must take into account the fact that most of the enrolled patients have had poor response to ERT/SRT (including 10 of the 12 naïve patients) and therefore may not represent the majority of the patients. Further studies are needed in never-treated patients as well as an oral, less expensive, alternative to unselected stable patients currently treated with ERT/SRT with a favorable response.

Comparison Of The Efficacy And Safety Of Secukinumab, Ustekinumab And Guselkumab For The Treatment Of Moderate To Severe Plaque Psoriasis: A Systematic Review

Psoriasis is a chronic inflammatory skin condition characterized by scaly erythematous patches or plaques affecting the extensor surfaces that are prominent but spreading to all areas of the body, including the flexor surfaces. Psoriasis occurs when the body's immune system attacks the skin;the interleukin (IL)-12 and IL-17/23 axes play a major role in its pathogenesis. Biologic therapies targeting IL-17 or IL-23 have emerged as an important treatment option for psoriasis and have led to substantial improvements in patients' quality of life. This systematic review aimed to evaluate the comparative efficacy and safety of secukinumab, ustekinumab and guselkumab for the treatment of moderate to severe plaque psoriasis. Based on the final analysis, there were 10 articles, namely 5 RCTs and 5 observational. We found that patients who were given secukinumab showed a rapid response, whereas guselkumab was superior in terms of long-term response (approximately 1 year) and complete remission compared to other biologics. Among all the biologics assessed, ustekinumab showed relatively low efficacy.

Rates of New Peanut Allergy and Discontinuation Following Introduction in High-Risk Infants

Rationale: Current guidelines recommend peanut introduction to high-risk infants. However, compliance and rates of new peanut allergy (PA) require further study. Methods: Participants aged 4-11 months with no prior peanut exposure and (i) diagnosis of non-peanut food allergy, (ii) moderate-severe atopic dermatitis, or (iii) first degree relative with PA were enrolled. PA status was determined by skin testing and food challenge. Participants without PA were advised to consume 2 grams of peanut protein three times/week. Monthly questionnaires were administered, with follow-up visits at 18 and 30 months. Results: At baseline, 35/326 (11%) participants were peanut allergic. Of 291 without PA, 78 (27%) discontinued peanut at least temporarily 115 times during follow-up because of suspected participant reaction (40%), fear of reaction (3%), reaction or fear of reaction in a family member (21%), participant refusal (9%), peanut introduction was too much work (3%), or other reasons (23%), including the COVID-19 pandemic. Six of 291 participants (2.1%) who consumed peanut developed PA (2 consistent with FPIES). Among 291 participants without PA at baseline, none of the 17 participants with initial skin prick test of at least 4 mm and <10 mm developed PA. Conclusions: New PA after early introduction recommendations was rare, confirming the LEAP study findings. Transient discontinuation was common, mostly due to suspected participant reaction. High-risk children may require substantial support to keep peanut in their diet.

Pneumopericardium in COVID-19 Infection

Pneumopericardium is a rare medical condition that occurs following trauma, surgery, or other medical interventions. The presence of pneumopericardium after COVID-19 pneumonia has been reported in some cases, and it has been explained that most cases could be self-limited. Here, we describe a 51-year-old man afflicted by pneumopericardium with COVID-19 infection. The patient had pneumopericardium and massive pericardial effusions, necessitating surgical strategies such as pericardial windows. This case highlights the potential severity of COVID-19. We also suggest that cardiologists pay attention to the possibility of pneumopericardium in cases with COVID-19 infection. © 2023, Iranian Heart Association. All rights reserved.

Post-COVID-19 non-traumatic iliopsoas hematoma: A case report

Background: Critically ill COVID-19 patients have an elevated risk of experiencing hypercoagulable conditions. Currently, many COVID-19 patients have been administered anticoagulation or antiplatelet therapies to lower the risk of systematic thrombosis. Iliopsoas hematoma is a potentially fatal and rare complication of bleeding disorders or anticoagulation therapy which sometimes grows to become clinically significant. The main purpose of this case review is to emphasize the importance of diagnosing iliopsoas hematomas and the possibility of antiplatelet contribution to its development. Case Presentation: We are reporting a rare presentation of non-traumatic iliopsoas hematoma in a non-anticoagulated patient. The patient is a 59-year-old male, with known type-2 diabetes, on oral hypoglycemic medications, 3-weeks post-COVID-19. He had started aspirin 81 mg orally, once daily, to prevent thrombotic events associated with COVID 19 infection, with no anticoagulant use and no other medications. He came in through the ED, presenting with two weeks history of progressive right lower limb weakness in which an iliopsoas hematoma diagnosis was confirmed based on radiological investigation. Conclusion: The possibility of iliopsoas hematoma should be considered in non-anticoagulated patients with no inherited or acquired coagulation disorders presenting with limb weakness. The link between antiplatelet use in a COVID-19 patient and the development of soft tissue bleeding (e.g., iliopsoas hematoma) must be studied further. © 2022 [The Author/The Authors]

NOISE POLLUTION AND ARTERIAL HYPERTENSION

Environmental noise significantly impacts human health and well-being. It is a widespread problem in Europe, where at least one in five people are exposed to harmful levels of noise. Hearing loss is the most known health effect related to noise exposure. There is, however, growing data that links noise exposure to hypertension, coronary artery disease, and stroke. According to some theories, this relationship may be explained by the indirect pathway of noise exposure, which can cause sympathetic and endocrine activation, as well as several cognitive and emotional responses, including annoyance. Noise exposure leads to stress reactions independent of cognitive involvement. There is a possibility that noise exerts its effects directly through synaptic interactions, as well as through cognitive and emotional effects. Epidemiological studies indicate that nocturnal noise exposure has more profound health consequences. Nighttime noise exposure is associated with an increase in heart rate due to sympathetic activation or parasympathetic withdrawal, and with an increase in blood pressure as well as endothelial dysfunction. Hypertension is a common condition and is an important risk indicator for other cardiovascular diseases. Previous studies showed an association between noise exposure, blood pressure and arterial hypertension. Meta-analysis of cross-sectional studies found an increase of hypertension prevalence per 10 dB increase in daytime average road traffic noise level. There is, however, some heterogeneity among these studies. Prospective studies have also found an association between aircraft noise exposure and hypertension, supporting the cross-sectional findings. The analyses, of data from the large Hypertension and Exposure to Noise near Airports (HYENA) study, showed that an increase in nocturnal aircraft noise exposure per 10 dB was associated with an increased incidence of hypertension. The meaningful effect of night-time aircraft noise on arterial hypertension was also observed in the prospective observation of the subset of individuals from that study. In a longitudinal observation of 420 participants, higher aircraft noise exposure during the night significantly associated with the incidence of hypertension. Previous cross-sectional case-control study conducted in 2015, in 2 suburban areas of Krakow, Poland, revealed an increase in blood pressure and arterial stiffness as determined by carotid - femoral pulse wave velocity in individuals exposed to increased aircraft noise levels. However, even short-term noise reduction, as experienced during the COVID-19 lockdown, may reverse those unfavorable effects. As a result of these observations, noise mitigation strategies are important for cardiovascular health.

CONSEQUENCES OF DISCONTINUING ANTIHYPERTENSIVE TREATMENT DURING THE FIRST WAVE OF A COVID-19 PANDEMIC

Arterial hypertension (AH), especially insufficiently and inadequately treated, is a disease with serious morbidity-mortality consequences. AH was the most common comorbidity in patients with COVID-19 infection. During the first wave of the COVID-19 pandemic, Slovakia has low number of COVID 19 patients. However, worldwide was reported 2-fold higher mortality in COVID 19 positive patients with untreated AH compared to patients with treated AH. Many patients have discontinued antihypertensive treatment due to changes in access to healthcare as well as the dissemination of unverified information. The aim of our study was to evaluate the AH treatment in patients during the first wave of the COVID-19 pandemic, to analyze the consequences of changes in AH treatment. It is a retrospective analysis of antihypertensive treatment of patients followed in the tertiary center. A total of 112 consecutive patients with AH who had a scheduled follow-up during the months of March-April 2020 were included. A telephone check-up was performed 6 months after the scheduled follow-up. These were patients with a mean age of 64 ± 18.1 years, 73 patients (65.2%) were male, and the mean number of antihypertensives per patient was 3.6 ± 2.2 drugs. Out of a total of 112 patients, 9 (8%) patients completely discontinued AH treatment, 15 (13.4%) patients discontinued ACEI / ARB without substitution, 5 (4.5%) patients discontinued ACEI / ARB with subsequent AH adjustment treatment. In the observed period March-April 2020, patients with newly diagnosed AH were absent. In our followed patient population (1.8%) were tested as COVID positive, 0 patients were hospitalized for COVID 19 infection. 4 (16,7%) patients overcame stroke, 1 (4.2%) patient overcame TIA, 1 (4.2%) was hospitalized for ACS, 2 (8.3%) for AF with rapid ventricular response, 2 (8.3%) for pulmonary edema, 2 (8.3%) patients died. In the group of patients who had adjusted treatment or did not discontinue AH treatment (a total of 88 patients) 1 (1.1%) patient overcame stroke, 1 (1.1%) was hospitalized for ACS, 1 (1.1%) for newly diagnosed AF, 1 (1.1%) patient died. Unjustified complete or partial discontinuation of antihypertensive treatment during the first wave of the COVID-19 pandemic has led to an increase in complications of arterial hypertension. Achieving BP targets should also be crucial during the COVID 19 pandemic.

The prevalence of rheumatoid arthritis (ra) flare post covid-19 vaccination in malaysian population and the associated risk factors

Background: Rheumatoid Arthritis (RA) flare post-COVID- 19 vaccination has been reported and poses a great concern among patients. This study aims to evaluate the prevalence of RA flare post COVID-19 vaccination and its associated risk factors. Method(s): This was a cross-sectional questionnaire-based study assessing RA flare based on patient self-report disease flare or documented physician assessment (physician-reported flare). The study was conducted from May to July 2022 in Hospital Putrajaya and recruited RA patients who received at least one dose of COVID-19 vaccine under the Malaysian National Vaccination Programme. Patient self-reported disease flare was defined as 'a sudden worsening of rheumatology condition or arthritis within 1 month post-vaccination' while physician-reported flare was defined as 'an increment of disease activity score 28-joint (DAS28 CRP/ESR) documented within 3 months post-vaccination' from either a scheduled or unscheduled clinic visit. Demographic data, vaccination history and disease parameters were retrieved from electronic medical records. Statistical analysis included descriptive and univariate analyses were performed using SPSS. Result(s): A total of 186 patients were enrolled. Majority (93%) were female with the mean age of 58 years old (standard deviation, SD 12.2). Most patients were seropositive (66% Rheumatoid factor, 63% anti-citrullinated peptide antibodies) with mean disease duration of 12 years (SD 7.7). Majority were on methotrexate (MTX) (71%), 21.5% were on leflunomide and only 4.8% were on biologics or targeted synthetic disease modifying anti-rheumatic drugs. A small proportion of patients were on steroids (14%). Half of the patients were in remission prior to vaccination. All patients completed 2 doses of vaccination in which 62% received Pfizer-BioNTech vaccine followed by Sinovac (coronaVac) vaccine (24.6%) and Oxford-AstraZaneca vaccine (13.4%). Only 80% received booster dose, of which 88.7% was Pfizer-BioNTech vaccine. A total of 52 patients who were on MTX therapy discontinued the drug post-vaccination for a week duration. The prevalence of flare was only 12.9% (n: 24) in which 14 were self-reported and 10 were physician-reported flares (4 severe flare, 6 mild-moderate flare). Majority of flares occurred during the first and second dose of vaccination with 29.2% respectively, and only 12.5% were reported after booster vaccination. There were no significant differences in the occurrence of flare post-vaccination between age, gender, disease activity prior to vaccination, types of vaccine, usage of MTX and steroids, and discontinuation of MTX post-vaccination. Conclusion(s): Prevelance of RA flare post-COVID- 19 vaccination is low and there were no significant associated risk factors identified in this study.

Cancer, Covid and Control of Ra - a Toxic Combination?

Case report - Introduction: This case highlights the dilemma of keeping rheumatoid arthritis disease under control in active cancer cases and establishing a consistent multidisciplinary dialogue during a pandemic and staffing crises. During chemotherapy and active cancer treatment, disease-modifying therapies (conventional and biologic) are often stopped. In some cases, the potential benefits versus risks of restarting usual therapies have to be balanced against risks of suppressing disease activity with highdose steroids. Risks of infection (common and atypical) need to be considered. Case report - Case description: A is a 67-year-old female nonsmoker diagnosed with seropositive rheumatoid arthritis (RF, anti - CCP positive) in 2008. Other conditions include type 2 diabetes, atrial fibrillation (on warfarin), hypothyroidism and obstructive sleep apnoea. Due to active disease, despite triple therapy (methotrexate, sulphasalazine and hydroxychloroquine), anti-TNF therapy (etanercept) commenced in 2009 with primary non-response. However, she responded well to B-cell therapy (rituximab) in conjunction with oral methotrexate (25mg weekly) receiving annual infusions from 2010 to 2016. In 2017, an elective sleeve gastrectomy procedure for high BMI was abandoned after peritoneal deposits of concern were noted. Histology and CT imaging were consistent with a primary peritoneal malignancy (Stage 3c low-grade serous adenocarcinoma). Treatment involved debulking surgery (total abdominal hysterectomy, bilateral salpinoophorectomy, omentectomy) and tamoxifen. Treatment for rheumatoid arthritis stalled during this period but as frequent steroids were required for active joint inflammation, in agreement with the oncologists, she had a rituximab cycle in 2018. Unfortunately, in 2019 she had signs of cancer progression (elevated tumour markers, CT imaging) and has subsequently started carboplatin chemotherapy. She has been unable to continue methotrexate or rituximab pending completion of the chemotherapy cycles (ongoing). However, her arthritis is now uncontrolled without increased steroids. Due to recurrent flares, her maintenance dose has been increased from 5mg to 7.5-10mg prednisolone daily until we can establish if it is safe and appropriate to recommence her usual arthritis regime. Even without disease-modifying therapy like methotrexate and rituximab, risk of infection (including atypical ones) is still significant with the combination of chemotherapy and steroids. Risk of progressive joint damage and adverse quality of life with active arthritis also needs to be considered. Staffing crises, exacerbated by COVID pandemic issues, have added to complexity of decision making and coordination of regular multidisciplinary discussions regarding treatment. Case report - Discussion: Cancer is a known association in rheumatoid arthritis patients with a twofold higher risk of lymphoma compared to the general population. Whether condition or treatment affects risk remains unclear as immune dysregulation is relevant in both autoimmunity and cancer. Paraneoplastic, recent onset arthritis, chemotherapy- or immunotherapy-induced arthralgia/arthritis are also well documented. This case had a seropositive rheumatoid arthritis phenotype quite a few years prior to cancer diagnosis. Primary peritoneal cancer is uncommon, often presenting as in this case as an incidental finding. It is usually treated like ovarian cancer Whilst methotrexate has been implicated in lung cancer, melanoma and non-Hodgkin lymphoma, overall safety data suggest any risk is quite low (e.g., EBV-associated lymphoproliferative disorders usually resolve with drug discontinuation). It is also a known chemotherapeutic agent. Anti-TNF treatment algorithms generally exclude patients with recent cancer. Rituximab, originally developed as a cancer drug, is not thought to affect risk of cancer development or progression. Treatment with disease-modifying therapy (conventional and biologics) is often withheld in patients with active malignancy undergoing chemotherapy due to a theo etical risk of potentiated immunosuppression and toxicity, particularly cytopaenias. However, maintaining arthritis control with glucocorticoids also has short- and long-term risks. Combining chemotherapy agents like carboplatin with methotrexate has been used for urothelial carcinoma and can be well tolerated with close monitoring of haematological parameters. Thus, it could be argued this patient is at risk of infections whichever treatment approach is taken and regaining control of arthritis with recommencement of methotrexate and rituximab is much better for her quality of life. Regular multidisciplinary discussions are important to outline risks versus benefits of combined treatment. This may be difficult in practice during staffing crises. Covid risk in patients receiving rituximab and/or chemotherapy, timing and response to COVID vaccination are also important considerations. Case report - Key learning points: . Primary peritoneal cancer is uncommon and can present as an incidental finding . Whilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of life . Morbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers - lack of "named" providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult.

Milrinone-induced platelet inhibition in patients supported on veno-aterial extracorporal membrane oxygenation: a case series

Case Report: Purpose: Milrinone is an inodilator that is used in the treatment of cardiogenic dysfunction and shock. It causes increased cardiac output by stimulating myocardial contractility, enhancing cardiac relaxation, and reducing afterload via phosphodiesterase III inhibition, preventing cyclic adenosine monophosphate (cAMP) degradation. Increased cAMP concentrations are known to inhibit platelet aggregation. Veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal treatment option for inotrope-refractory cardiogenic shock and is often used in conjunction with inodilators. Often, patients supported on ECMO require systemic anticoagulation to prevent clotting complications. Therefore, thromboelastography (TEG) with platelet mapping is used to help gauge a patient's clotting status and gives clinicians information about the degree of platelet inhibition present. We present the case of two patients, both supported on VA-ECMO, who developed platelet inhibition with clinically significant bleeding while on milrinone, requiring the cessation of the milrinone infusion. Cases: First, we present an adult female in her fourth decade of life who required VA-ECMO for Covid-19 ARDS and cardiogenic shock. TEG platelet mapping was obtained for clinically significant bleeding from her trachea and gastrointestinal tract. Ten days after starting milrinone, adenosine-5'-diphosphate (ADP) inhibition was elevated at 67.4% and arachidonic acid (AA) inhibition normal at 1.8%. Twenty days after starting milrinone, ADP inhibition was 93.3% and AA inhibition was 76.4%. Milrinone discontinued and repeat TEG platelet mapping (10 days after discontinuation) showed ADP inhibition of 76.8% and AA inhibition of 0%. Her lowest ADP inhibition was 41.9%, approximately 1 month after milrinone discontinuation. Milrinone again attempted and ADP inhibition was 87.9% and AA inhibition 89.2% within 24 hours of initiation. No data available for platelet inhibition prior to starting milrinone. Next, we present a 9 year old female with acute myeloid leukemia who required VA-ECMO for septic shock. Initial TEG platelet mapping, obtained 2 days after milrinone initiation, showed ADP inhibition of 43.6% and AA inhibition of 98.7%. Two days after discontinuation of milrinone, her ADP inhibition was 19.6% but AA inhibition remained elevated at 91.9%. However, after 4 days off milrinone, her ADP inhibition was normal at 15.5% and AA inhibition mildly elevated at 33.6%. No data available for platelet inhibition prior to starting milrinone. Conclusion(s): Milrinone is a known platelet inhibitor due to increased intracellular cAMP concentrations. For patients on ECMO and milrinone, care should be given to the degree of platelet inhibition and potential risk of clinically significant bleeding. Further studies are needed to further investigate the correlation between milrinone, platelet inhibition, and clinically significant bleeding in ECMO patients. Copyright © 2023 Southern Society for Clinical Investigation.

A Virulent Disease Called Monkeypox: A Case Report of Countries in Africa Where the Disease is Endemic

Cases of Monkeypox continue to rise and the World Health Organization (WHO), declared it a public health emergency of international concern (PHEIC). A virus called monkey pox causes the disease and it is zoonotic. The epidemiological surveillance from 1981-1986 in the Democratic Republic of Congo (DRC) a country in Africa were the disease is endemic, documented only 338 cases. Previously, 90% of the affected persons were children approximately 15 years of age at least in the endemic countries in Africa. Beyond Africa, 99% cases of the current outbreak were found in men and of those, 98% involved men who have sex with men implying it is being transmitted through sexual activities. Crowded living quarters, poor hygiene, discontinuation of the smallpox vaccination, amongst others were implicated in the human to human transmission. The symptoms of the disease includes, viremia with 1-2 days of fever and lymphadenopathy before lesions appear. Patients at this stage may be contagious. For treatments, there are no known clinically proven treatments for the disease. Polymerase chain reaction (PCR) amplification are used for specific diagnosis and smallpox vaccines are effective against the disease. Table 1 shows cases from Africa union member countries (AUMC), and Congo Republic, Cameroon and DRC, have a high cumulative frequency (CFR) of occurrence (43, 5.6 and 4.1%), respectively (see Fig 2). The vaccine is not readily available in these endemic countries thus, donors countries needs to collaborate with researchers and health officials to determine what these endemic countries in the global south requires towards enabling scale up in response to this disease. Copyright © 2022 iGlobal Research and Publishing Foundation. All rights reserved.

Donor-specific tolerance induction by combined kidney and hematopoietic stem cell transplantation

Background: Long-term survival of kidney allografts is limited by either inadequately controlled rejection and/or by side effects of long-term immunosuppression (drug toxicity, infections and neoplasia). Induction of donor-specific tolerance would resolve most, if not all of these limitations. Here, we report on 6 patients included in the first European trial of combined kidney and hematopoietic stem cell transplantation (HSCT;swisstolerance. CH). Methods or Case description: Six patients (3 female / 3 male) underwent combined kidney and hematopoietic stem cell transplantation from their HLA-identical living siblings between 2016 and 2022. Conditioning therapy for HSCT and immunosuppression was performed according to the Stanford protocol including total lymphoid irradiation, anti-thymocyte globulin followed by corticosteroids (3 days), mycophenolate (1 months) and cyclosporine for 6-15 months. After 9-15 months all immunosuppression was withdrawn. Results or Learning points: Five out of six patients were completely withdrawn from all immunosuppression (follow-up between 6 years and 4 months). No rejection or graft-versus-host disease episodes and no relevant infections occurred. Initial donor chimerism was seen in all patients. However, in 5/6 patients the chimerism level was declining, whereas one patient remained a stable mixed chimera. Specificity of tolerance was tested by molecular microscope analysis (absence of rejection signature) and by successful SARS CoV2 vaccination in some of the patients. One patient experienced a relapse of her primary glomerulonephritis in the allograft. She developed proteinuria, but renal function remained normal so far. Conclusion(s): Combined HSCT and kidney transplantation from the same living donor provides tolerance to a kidney allograft. This tolerance is donor-specific, as shown by protective immune responses against a SARS-CoV2-specific vaccine and absence of "molecular rejection".

Withdrawal from dialysis in Switzerland between 2014 and 2021

Background: A recent Dutch study suggests that dialysis withdrawal has increased over the last years. The aims of this study were to investigate whether this is also the case in Switzerland, and to identify factors associated with withdrawal. Methods or Case description: In this retrospective study, data were retrieved from the Swiss Dialysis Registry (srrqap). Annual death rates and causes of death were analyzed between 2014-2021. We compared clinical characteristics of patients who were withdrawn for medical/other reasons or who withdrew from dialysis with those who had another cause of death and with those who stayed alive. Results or Learning points: A total of 7'246 incident patients on hemodialysis or peritoneal dialysis between 2014-2021 were included;of those, 2'325 patients died. In 2020, there was an above-average number of deaths, due to the coronavirus pandemic. Dialysis withdrawal because the patient refused further treatment represented 8.3-13.3% of all causes of death. Withdrawal by the patient did not increase throughout the study period, but withdrawal for medical/other reasons increased from 6.2 to 8.9% (see figure). Patients who died because of withdrawal from dialysis were significantly older and longer on dialysis than those with other causes of death, and had suffered less often from COVID-19. In multivariate regression analysis adjusted for age, sex, and Charlson score, testing negative for coronavirus was the only factor associated with withdrawal by the patient, whereas withdrawal for medical or other reason was also associated with higher age. Conclusion(s): Unlike the Netherlands, dialysis withdrawal is not the leading cause of death in Switzerland, and withdrawal by the patient has not increased, not even during the COVID-19 epidemic. However, the percentage of patients who was withdrawn for medical/other reasons increased during this period, for unclear reasons. The only risk factors for withdrawal were higher age and - surprisingly - testing negative for the coronavirus.

Evaluation of a Propofol Dosing Capping Strategy in Patients with Hypertriglyceridemia and Covid-19

INTRODUCTION: Propofol can be associated with hypertriglyceridemia (HTG), which may lead clinicians to change to non-preferred sedatives such as benzodiazepines (BZD) to avoid HTG complications. Patients with COVID-19 have been observed to require increased doses and durations of sedatives, which may increase the risk of HTG development. The purpose of this study was to evaluate a dose capping strategy of propofol versus discontinuation on minimizing BZD exposure in ventilated patients. METHOD(S): This retrospective study included patients with COVID-19 and HTG after receiving propofol between March 1, 2020 and April 30, 2021. HTG was defined as serum triglycerides (TG) greater than or equal to 500 mg/dL. The propofol dose cap used in select patients was a reduced maximum dose of 30 to 40 mcg/kg/min. The remainder of patients had propofol discontinued (standard of care). Descriptive statistics were used to evaluate differences in propofol duration, BZD doses, and intensive care unit (ICU) length of stay (LOS) between groups. Incidence of pancreatitis was also evaluated. RESULT(S): Seventy-one patients were included. The propofol dose cap was used in twenty patients. The mean baseline TG were similar in both groups, 256 mg/dL (standard deviation (SD)=125) in the propofol dose cap group compared to 252 mg/dL (SD=104) in the standard group (P=0.9). Propofol was continued four days longer after dose capping, with a median duration of 11.7 vs. 7.4 days, P=0.255. Cumulative intermittent doses of BZDs were higher in the dose cap cohort (average cumulative dose 28mg vs. 20mg, P=0.245), however BZD continuous infusion cumulative doses were lower (1214mg vs. 1377mg, P=0.778). Median ICU LOS was similar between groups (20.4 vs. 20.9 days, P=0.451). No patients in either group developed pancreatitis. CONCLUSION(S): The dose capping strategy allowed for clinicians to continue using propofol for sedation in mechanically ventilated patients with COVID-19 and HTG. This in turn helped minimize BZD exposure with no evidence of HTG associated adverse effects such as pancreatitis. Future investigation in a larger population is warranted to determine the dose cap impact on clinical outcomes, such as incidence of delirium and length of mechanical ventilation.

Safety of Dexmedetomidine Administered for Alcohol Withdrawal Syndrome to Nonintubated Icu Patients

INTRODUCTION: Dexmedetomidine is administrated in the ICU to treat adrenergic hyperactivity associated with alcohol withdrawal syndrome (AWS). Reduced ICU bed availability and drug shortages during the COVID-19 pandemic have spurred interest in mitigation strategies. The objective of this study was to develop preliminary data on the safety of dexmedetomidine when administered for AWS in nonintubated patients in order to develop a protocol for its use outside of the ICU. METHOD(S): Patients >=18 years of age admitted to an ICU for AWS and received dexmedetomidine between January 2020 and January 2022 were included. Patients were excluded if they required invasive mechanical ventilation or received dexmedetomidine for indications other than AWS. Bradycardia was defined as a heart rate < 40 beats per minute and hypotension as a systolic blood pressured < 80 mmHg. Heart block was identified using 12-lead electrocardiograms. Need for intervention for adverse drug effects was also recorded. Continuous data are reported as median (IQR) and nominal or categorical data as number (%). RESULT(S): Of the 204 patients screened, 148 (73%) were excluded for invasive mechanical ventilation and 8 (4%) for receipt of dexmedetomidine for non-AWS indications, leaving 48 (24%) evaluable patients. Most were male (n=36, 75%), white (n=43, 90%) and non-Hispanic/ Latino (n=47, 98%). Patients were bedded in the emergency department (n=20;42%), an intermediate care unit (n=11;23%), an outside hospital (n=10;21%), a general medical floor (n=6;12%), or perioperative unit (n=1, 2%) prior to ICU admission. The median initial dexmedetomidine dose was 0.35 (0.1, 0.5) mcg/kg/hr and the maximum dose was 1.2 (0.8, 1.4) mcg/ kg/hr. Time to the maximum dose was 2.2 (0.5, 8.5) hours and the total dexmedetomidine infusion duration was 25 (13, 40) hours. Hypotension occurred in 10 (21%) patients-only 2 (4%) required fluid administration, none received pressors or dose reduction. Bradycardia and heart block were not observed. CONCLUSION(S): Dexmedetomidine administration for AWS in non-intubated ICU patients was safely accomplished in 95% of patients with only 4% of the cohort developing hypotension requiring fluid administration. These results will be used to develop a protocol for dexmedetomidine administration in non-ICU areas for AWS.

Evaluation of Response Rate to Fixeddose Inhaled Epoprostenol

INTRODUCTION: Inhaled epoprostenol (iEPO) is adjunctive therapy for acute respiratory distress syndrome (ARDS) in addition to prone positioning and neuromuscular blockade. Previous studies report mixed improvement in PaO2/FiO2 (P:F) ratios using fixed-dose and weight-based protocols. The aim of this study was to evaluate patient response rate to fixed-dose iEPO via palladium vibrating mesh nebulizer and the rate of rebound hypoxemia following abrupt iEPO discontinuation without titration per local protocol. METHOD(S): Single-center, retrospective, descriptive study of adult patients admitted to an ICU at a Veterans Affairs hospital who received iEPO for ARDS between 5/23/14 and 4/1/21. Patients were included if they received iEPO 1500 mcg/75 mL (120 mcg load, then 160 mcg/hr continuous nebulization) for at least 12 hours. Patients receiving iEPO for an indication other than ARDS were excluded. Response was defined as an increase in P:F >10% within 12 hours. Safety was assessed via decline in P:F after iEPO stop. RESULT(S): Of the 29 patients included, 72.4% had a baseline P:F < 100 mmHg (median 76.8, range 38-250). Diagnosis included direct ARDS in 44.8% and COVID ARDS in 24.1%. Adjunctive therapies included paralytics (58.6%), corticosteroids (44.8%) and pronation (27.6%). Seventeen patients (58.6%) were responders with a median P:F increase of 41.6% (range 11.6-322.1) at 3.8 hours (0.1-20.3) after iEPO initiation. iEPO was given for a median of 3 days (0.5-18.6) overall, and 3.4 days (0.5-8.7) in non-responders. The median best P:F during iEPO was 140 mmHg (59.9-423.0) at 24 hours (1.1-299). Eight of 14 patients with an ABG drawn a median of 7.6 hours after iEPO cessation had a drop in P:F. Other adverse outcomes following iEPO initiation included ICU mortality in 65.5% and new hypotension in 67%. CONCLUSION(S): In a small heterogenous cohort of patients with ARDS, fixed-dose iEPO had a modest response rate. A majority of patients who survived to iEPO cessation without down-titration experienced a drop in P:F. Protocol revision to include guidance on therapeutic response and down-titration may be warranted.

Pharmacist Optimization of Bowel Preparations in the Critically Ill: The Poopy Study

INTRODUCTION: Critically ill patients undergo stressful states while in the intensive care unit (ICU) and thus have alterations in bowel habits, including constipation in 20- 83% and diarrhea in 3.3-78%. Patients frequently receive opioid analgesics to assist with sedation and pain control. Appropriate bowel management is essential to prevent further complications during the ICU stay. The purpose of this study is to examine the various bowel preparations (BP) used in ICU patients, time to first bowel movement after initiation or escalation of a BP, and reason for BP discontinuation. METHOD(S): This multi-center, multi-ICU, retrospective observational review evaluated tele-critical care pharmacist interventions documenting initiation or change in BP from January 2, 2021 to June 30, 2021. Interventions were excluded if the BP was renewed, duplicate therapy and/or change in formulation. Descriptive statistics were used to describe the data. RESULT(S): One hundred ninety-six unique patients had at least one BP intervention. Baseline characteristics include 55% male, average age of 64 years, a BMI of 32.9, and 66% COVID-19 positive. One hundred seventy-four unique patients had a BP initiated or added on to current therapy, while 62 unique patients had current therapy escalated. The median days to first bowel movement after initiation or addition of a BP was 5.4 days (range 0-19). Ninety-eight percent of patients received an opioid, either continuous infusion or oral, and 90% received enteral nutrition. Docusate and senna were the primary BPs added when a regimen was initiated. Then, polyethylene glycol was added as the next BP. Lactulose and bisacodyl suppositories were added as 4th line treatment if the patient had not experienced a bowel movement. Methylnaltrexone was used in 1 patient. Fifty-two unique patients had one or more medications from their current bowel regimen discontinued due increased stool output, diarrhea, multiple bowel movements within last 24 hours, or the patient refusing the medication. CONCLUSION(S): Initiation of BPs in critically ill patients, especially if receiving an opiate, may be delayed. Bowel regimen initiation should be considered when the patient is placed on opiate therapy. If the patient continues to have a delayed response to therapy, prompt escalation of therapy may be warranted.

Effect of Midodrine in Covid-19 Patients with Septic Shock on Time to Vasopressor Discontinuation

INTRODUCTION: Patients with COVID-19 in the intensive care unit (ICU) often require prolonged use of intravenous (IV) vasopressors which become a barrier to intensive care unit (ICU) discharge. The goal of this study is to describe the effect of midodrine, an alpha-1 agonist, on time to IV vasopressor discontinuation in COVID-19 patients in the ICU. METHOD(S): This study was an IRB-approved retrospective chart review conducted at a community, tertiary care hospital between January 2020 until November 2021. Eligible participants included hypotensive patients aged 18 years or older who were admitted to an ICU on at least 0.1 mcg/kg/ min of norepinephrine for 24hrs with a diagnosis of septic shock and COVID-19. Pearson Chi-Square and Independent- Samples Mann-Whitney U Test were used to analyze baseline characteristics, ICU length of stay, and time to IV vasopressor discontinuation in patients that received at least one dose of midodrine and patients on comparable IV vasopressors not started on midodrine. RESULT(S): 70 patients were included in the study with 35 patients in the midodrine group and 35 patients in the control group. The median time to IV vasopressor discontinuation was 13 days for the midodrine group and 8 days for the control group (p < 0.001), but there were less patients started on a second IV vasopressor in the midodrine group. Median time of initiation of midodrine was 9 days and IV vasopressors were discontinued at a median of 4 days after starting midodrine. The mean ICU length of stay and Hospital length of stay were 26 days & 32 days in the midodrine group and 15 days & 21 days in the control group (p < 0.001). The average dose of midodrine was 10 mg per day. CONCLUSION(S): The initiation of midodrine in COVID-19 patients with septic shock was not found to decrease total time to IV vasopressor discontinuation. Although, there were less patients started on a second IV vasopressor in the midodrine group.