Quality of Life Analysis of Patients Treated with Percutaneous Hepatic Perfusion for Uveal Melanoma Liver Metastases.

PURPOSE: Percutaneous hepatic perfusion with melphalan (M-PHP) is a minimally invasive therapy with proven efficacy in patients with uveal melanoma (UM) liver metastases. M-PHP is associated with a short hospital admission time and limited systemic side effects. In this study, we assessed quality of life (QoL) in UM patients treated with M-PHP. MATERIALS AND METHODS: A prospective, single-center study including 24 patients treated with M-PHP for UM metastases to the liver. QoL questionnaires were collected at baseline, on day 2/3 after M-PHP, and on day 7 and day 21 after M-PHP, according to study protocol. The results were scored according to EORTC-QLQ C30 global health status (GHS), functional scales, and symptom scales. The difference in scores at baseline and subsequent time points was analyzed with the Wilcoxon signed-rank test and multiple testing Bonferroni correction. Adverse events (AE) were registered up to 30 days after M-PHP according to CTCAE v5.0. RESULTS: Twenty-four patients (14 males; median age 63.0 years) completed 96 questionnaires. Most scores on all scales declined on day 2/3 after M-PHP. On day 21 after M-PHP, 12 out of 15 scores returned to baseline, including median GHS scores. Three variables were significantly worse on day 21 compared to baseline: fatigue (6-33; p = 0.002), physical functioning (100 vs 86.7; p = 0.003), and role functioning (100 vs 66.7; p = 0.001). Grade 3/4 AEs consisted mainly of hematological complications, such as leukopenia and thrombopenia. CONCLUSION: M-PHP causes fatigue and a decline in physical and role functioning in the 1st weeks after treatment, but GHS returns to baseline levels within 21 days. LEVEL OF EVIDENCE 3: Cohort study.

The effect of six-month oral vitamin K supplementation on calcification propensity time in individuals with type 2 diabetes mellitus: A post hoc analysis of a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Experimental studies suggested that vitamin K supplementation may retard arterial calcification. Recently, serum calcification propensity time (T50) has been suggested as a functional biomarker for arterial wall calcification propensity. In this post-hoc analysis of a clinical trial, we evaluated the effect of six-month oral vitamin K supplementation on T50 and assessed the correlation between T50 and imaging arterial calcification parameters in people with type 2 diabetes (T2DM). METHODS: This double-blind, randomized, placebo-controlled trial included 68 participants (age = 69 ± 8 years, 76% male) with T2DM. Participants were assigned to menaquinone-7 (360 µg/day; n = 35) or placebo (n = 33). T50 was measured via nephelometry in serum collected at baseline, three and six months. Arterial calcification was measured at baseline and six months via 18F-Na PET-CT and conventional CT using Target-to-Background ratio (TBR) and Agatston score. Longitudinal analysis of covariance adjusted for baseline T50 was used to study the treatment effect. Spearman's correlation was used to assess the correlation between T50 and imaging calcification parameters. RESULTS: Median baseline T50 was similar in the vitamin K (350 [321-394] minutes) and placebo groups (363 [320-398]). There was no significant difference in T50 between treatment arms over time (ẞ = 1.00, 95%C.I. = 0.94-1.07, p = 0.982). The correlation coefficient of T50 with TBR and Agatston score at baseline were -0.185 (p = 0.156) and -0.121 (p = 0.358), respectively. CONCLUSIONS: No effect of vitamin K supplementation on T50 was observed in T2DM. Moreover, T50 did not correlate with TBR and Agatston score. Further research on vitamin K in arterial calcification and on the validity of T50 as arterial calcification marker is warranted.

Quantum simulation of thermodynamics in an integrated quantum photonic processor.

One of the core questions of quantum physics is how to reconcile the unitary evolution of quantum states, which is information-preserving and time-reversible, with evolution following the second law of thermodynamics, which, in general, is neither. The resolution to this paradox is to recognize that global unitary evolution of a multi-partite quantum state causes the state of local subsystems to evolve towards maximum-entropy states. In this work, we experimentally demonstrate this effect in linear quantum optics by simultaneously showing the convergence of local quantum states to a generalized Gibbs ensemble constituting a maximum-entropy state under precisely controlled conditions, while introducing an efficient certification method to demonstrate that the state retains global purity. Our quantum states are manipulated by a programmable integrated quantum photonic processor, which simulates arbitrary non-interacting Hamiltonians, demonstrating the universality of this phenomenon. Our results show the potential of photonic devices for quantum simulations involving non-Gaussian states.

FDA-approved drug screening in patient-derived organoids demonstrates potential of drug repurposing for rare cystic fibrosis genotypes.

BACKGROUND: Preclinical cell-based assays that recapitulate human disease play an important role in drug repurposing. We previously developed a functional forskolin induced swelling (FIS) assay using patient-derived intestinal organoids (PDIOs), allowing functional characterization of CFTR, the gene mutated in people with cystic fibrosis (pwCF). CFTR function-increasing pharmacotherapies have revolutionized treatment for approximately 85% of people with CF who carry the most prevalent F508del-CFTR mutation, but a large unmet need remains to identify new treatments for all pwCF. METHODS: We used 76 PDIOs not homozygous for F508del-CFTR to test the efficacy of 1400 FDA-approved drugs on improving CFTR function, as measured in FIS assays. The most promising hits were verified in a secondary FIS screen. Based on the results of this secondary screen, we further investigated CFTR elevating function of PDE4 inhibitors and currently existing CFTR modulators. RESULTS: In the primary screen, 30 hits were characterized that elevated CFTR function. In the secondary validation screen, 19 hits were confirmed and categorized in three main drug families: CFTR modulators, PDE4 inhibitors and tyrosine kinase inhibitors. We show that PDE4 inhibitors are potent CFTR function inducers in PDIOs where residual CFTR function is either present, or created by additional compound exposure. Additionally, upon CFTR modulator treatment we show rescue of CF genotypes that are currently not eligible for this therapy. CONCLUSION: This study exemplifies the feasibility of high-throughput compound screening using PDIOs. We show the potential of repurposing drugs for pwCF carrying non-F508del genotypes that are currently not eligible for therapies. ONE-SENTENCE SUMMARY: We screened 1400 FDA-approved drugs in CF patient-derived intestinal organoids using the previously established functional FIS assay, and show the potential of repurposing PDE4 inhibitors and CFTR modulators for rare CF genotypes.

Left atrial appendage volume as a prognostic Indicator of long-term mortality in Cancer survivors treated with thoracic radiation.

BACKGROUND: Cancer survivors with prior chest radiation therapy (CXRT) frequently present with atrial fibrillation, heart failure, and have higher overall long-term mortality. There are no data examining the utility of left atrial (LA) and LA appendage (LAA) volume-indices to predict clinical outcomes in these patients. OBJECTIVES: We examined the prognostic value of cardiac phase-dependent 3-D volume-rendered cardiac computerized tomography (CT)-derived LA and LAA volume-indices to predict mortality and major adverse cardiac events (MACE) in cancer survivors treated with thoracic irradiation. METHOD: We screened 625 consecutive patients with severe aortic stenosis who had undergone transcatheter aortic valve replacement from 2012 to 2017. Based on the gated cardiac CT image quality, we included 184 patients (CXRT:43, non-CXRT:141) for further analysis. We utilized multiplane-3D-reconstructed cardiac CT images to calculate LA and LAA volume-indices, and examined the prognostic role of CCT-derived LA and LAA volume-indices in predicting the all-cause mortality, cardiovascular (CV) mortality, and MACE. We used multivariate cox-proportional hazard analysis to identify the clinical predictors of survival. RESULTS: Overall, the CXRT group had significantly elevated LAA volume-index compared to non-CXRT group (CXRT:11.2 ± 8.9 ml/m2; non-CXRT:8.6 ± 4.5 ml/m2, p = 0.03). On multivariate cox-proportional hazard analysis, the elevated LAA volume and LAA volume-index were the strongest predictors of reduced survival in CXRT group compared to non-CXRT group (LAA volume: RR = 1.03,95% CI 1.0-1.01, p = 0.01; and LAA volume index: RR = 1.05, 95% CI 1.0-1.01, p = 0.03). LAA volume > 21.9 ml was associated with increased mortality. In contrast, LA volume was not a significant predictor of mortality. CONCLUSION: We describe a novel technique to assess LA and LAA volume using 3-D volume-rendered cardiac CT. This study shows enlarged LAA volume rather than LA volume carries a poor prognosis in cancer-survivors treated with prior CXRT. Compared to conventionally reported markers, LAA volume of > 21.9 ml was incremental to that of other risk factors.

Combining Melphalan Percutaneous Hepatic Perfusion with Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety and Efficacy Data from the Phase Ib Part of the Chopin Trial.

PURPOSE: To define a safe treatment dose of ipilimumab (IPI) and nivolumab (NIVO) when applied in combination with percutaneous hepatic perfusion with melphalan (M-PHP) in metastatic uveal melanoma (mUM) patients (NCT04283890), primary objective was defining a safe treatment dose of IPI/NIVO plus M-PHP. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03). Secondary objective was response rate, PFS and OS. MATERIALS AND METHODS: Patients between 18-75 years with confirmed measurable hepatic mUM according to RECIST 1.1 and WHO performance score 0-1 were included. Intravenous IPI was applied at 1 mg/kg while NIVO dose was increased from 1 mg/kg in cohort 1 to 3 mg/kg in cohort 2. Transarterial melphalan dose for M-PHP was 3 mg/kg (maximum of 220 mg) in both cohorts. Treatment duration was 12 weeks, consisting of four 3-weekly courses IPI/NIVO and two 6-weekly M-PHPs. RESULTS: Seven patients were included with a median age of 63.6 years (range 50-74). Both dose levels were well tolerated without dose-limiting toxicities or deaths. Grade III/IV adverse events (AE) were observed in 2/3 patients in cohort 1 and in 3/4 patients in cohort 2, including Systemic Inflammatory Response Syndrome (SIRS), febrile neutropenia and cholecystitis. Grade I/II immune-related AEs occurred in all patients, including myositis, hypothyroidism, hepatitis and dermatitis. There were no dose-limiting toxicities. The safe IPI/NIVO dose was defined as IPI 1 mg/kg and NIVO 3 mg/kg. There was 1 complete response, 5 partial responses and 1 stable disease (3 ongoing responses with a median FU of 29.1 months). CONCLUSION: Combining M-PHP with IPI/NIVO was safe in this small cohort of patients with mUM at a dose of IPI 1 mg/kg and NIVO 3 mg/kg.

Role Of Ovarian Metastases In Colorectal Cancer (ROMIC): a Dutch study protocol to evaluate the effect of prophylactic salpingo-oophorectomy in postmenopausal women.

BACKGROUND: The mean incidence of ovarian metastases (OM) in patients with colorectal cancer (CRC) is 3.4%. The 5-year survival of these patients, even when operated with curative intent, is remarkably low. The lifetime risk of ovarian cancer is approximately 1.3%. Prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries and fallopian tubes) could reduce the number of CRC patients that develop OM after removal of the primary tumor, as well as preventing the occurrence of primary ovarian cancer. Recently, the care pathway for CRC has been changed in several hospitals in line with the updated Dutch guideline. The possibility of PSO is now discussed with postmenopausal CRC patients in these hospitals. The aims of the current study are firstly to estimate the incidence of OM and primary ovarian cancer in postmenopausal patients with CRC, and secondly to evaluate the effect of PSO in these patients. METHODS: An information bulletin and decision guide on this topic was implemented in several Dutch hospitals in 2020. Post-decision outcomes will be collected prospectively. The study population consists of postmenopausal (≥ 60 years of age) patients that are operated with curative intent for CRC. Based on their own preference, patients will be divided into two groups: those who choose to undergo PSO and those who do not. The main study parameters are the reduction in incidence of ovarian malignancies (metastatic or primary) following PSO, and the number needed to treat (NNT) by PSO to prevent one case of ovarian malignancy. DISCUSSION: This will be the first study to evaluate the effect of PSO in postmenopausal CRC patients that is facilitated by an altered CRC care pathway. The results of this study are expected to provide relevant information on whether PSO adds significant value to postmenopausal patients with CRC. TRIAL REGISTRATION: International Clinical Trials Registry Platform, NL7870. Registered on 2019 July 12. URL of trial registry record: https://trialsearch.who.int/Trial2.aspx?TrialID=NL7870 . PROTOCOL VERSION: 1.0, date 2021 June 8.

Early senior decision-making in acute medicine: a critical review of health policy and implications for practice.

UK urgent care health policies advocate senior clinical decision-making at the point of referral into the system. The costs of employing senior clinicians in this role are substantial with little evidence of the value they bring over other strategies, particularly for patient outcomes. We sought to explore current remote and ambulatory emergency care decision-making in acute medical care in a large central healthcare system - NHS Scotland. We found that many sites use remote decision-making for some allocation decisions. However, involvement of clinical expertise varies, and available decision-aids are few. There is also variation in access to resources that facilitate non-admission. Research into the value that senior clinicians bring to this task over other strategies is required.

Ovarian metastases in young women with colorectal cancer: a retrospective multicenter cohort study.

BACKGROUND AND PURPOSE: Previous studies indicated that approximately 3.4% of female colorectal cancer (CRC) patients are at increased risk of developing ovarian metastases (OM). It has been suggested that young women more frequently develop this form of metastatic disease. METHODS: This study evaluated, in 6 Dutch hospitals, the proportion of young women with CRC who developed OM. RESULTS: In a cohort of 200 young (age ≤ 55) women with CRC, the proportion of patients diagnosed with synchronous or metachronous OM was calculated. This study revealed that 5% (n = 10) of young female CRC patients developed ovarian metastases resulting in a 5-year overall survival rate of approximately 40%. Furthermore, six patients had concurrent peritoneal metastases, five patients had bilateral ovarian metastases, and five patients had synchronous metastases, while the median time of the occurrence of metachronous metastases (n = 5) was 19 months. CONCLUSION: This retrospective multicenter cohort study indicates that 5% of young women with CRC either present with or develop OM. This result appears to be clinically relevant and demonstrates the need for improved surveillance for young women diagnosed with CRC.

Primary ovarian cancer after colorectal cancer: a Dutch nationwide population-based study.

BACKGROUND AND PURPOSE: Women with colorectal cancer (CRC) are at risk not only of developing ovarian metastases, but also of developing a primary ovarian malignancy. Several earlier studies have in fact shown a link between the development of primary ovarian cancer and CRC. The purpose of this study was therefore to determine the risk of developing a primary ovarian cancer in women with prior CRC compared to the general population. METHODS: Data from the Netherlands Cancer Registry were used. All women diagnosed with invasive CRC between 1989 and 2017 were included. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years were calculated. RESULTS: During the study period, 410 (0.3%) CRC patients were diagnosed with primary ovarian cancer. Women with CRC had a 20% increased risk of developing ovarian cancer compared to the general population (SIR = 1.2, 95% CI: 1.1-1.3). The AER of ovarian cancer was 0.9 per 10,000 person-years. The risk was especially increased within the first year of a CRC diagnosis (SIR = 3.3, 95% CI: 2.8-3.8) and in women aged ≤ 55 years (SIR = 2.0, 95% CI: 1.6-2.6). CONCLUSION: This study found a slightly increased risk of primary ovarian cancer in women diagnosed with CRC compared to the general population. However, this may be partly attributable to surveillance or detection bias. Nevertheless, our findings could be helpful for patient counseling, as CRC patients do not currently receive information concerning the increased risk of ovarian cancer.

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial.

BACKGROUND: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease. METHODS: Open-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics (t-test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves. DISCUSSION: This is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT04283890 . Registered as per February 2020 - Retrospectively registered. EudraCT registration number: 2018-004248-49. Local MREC registration number: NL60508.058.19.

Partial Right Atrial Inflow Occlusion for Transient Systemic Hypotension During Deployment of Thoracic Stentgrafts.

PURPOSE: Temporary balloon occlusion of the inferior vena cava to lower cardiac output is a relatively infrequently used technique to induce controlled systemic hypotension. In this technical note, we describe the feasibility, reliability, and safety of partial occlusion of right atrial inflow and the effect on systemic blood pressure during the deployment of a thoracic stentgraft. MATERIALS AND METHODS: Twenty consecutive patients undergoing thoracic endovascular aortic repair, with proximal landing in zone 0-3 of the thoracic aorta, were prospectively included. Right atrial inflow occlusion was performed with a compliant occlusion balloon. RESULTS: Median time to reach a mean arterial pressure of 50 mmHg was 43 s. Median recovery time of blood pressure was 42 s. CONCLUSION: Partial right atrial inflow occlusion with an occlusion balloon is feasible with reliable results and without procedure-related complications.

Epipericardial Fat Necrosis: A Concise Review of Literature.

Epipericardial fat necrosis (EFN) is an inflammatory process that occurs in the mediastinal fat surrounding the heart. It is a rare cause of acute chest pain and mimics more ominous clinical conditions such as acute coronary syndrome, aortic dissection, and pulmonary embolism. Clinicians are often not familiar with this condition due to its infrequent occurrence, and traditional textbooks of medicine and cardiology have not covered this topic adequately. In the past, EFN had been managed primarily with thoracotomy and surgical excision. This has changed with advances in imaging techniques and their more frequent utilization. Computed tomography (CT) of the chest is essential for the diagnosis of EFN as it allows for the evaluation of the nature and precise location of the lesion. Magnetic resonance imaging helps to differentiate EFN from other mediastinal fatty lesions such as lipomas or liposarcomas. The clinical presentation of acute chest pain along with CT findings of the encapsulated fatty pericardial lesion is adequate for diagnosis. Our review describes the emerging role of imaging in diagnosis and change in management over the last few years.

Optical characterization of non-thermal plasma jet energy carriers for effective catalytic processing of industrial wastewaters.

An argon plasma jet was sustained in open air and characterized for its chemical composition. The optically characterized plasma jet was used to treat industrial wastewater containing mixed textile dyes and heavy metals. Since plasma jet produces UV-radiations, the photocatalytic TiO2 was used to enhance plasma treatment efficiency especially for degradation of dyes. Mixed anatase and rutile phases of TiO2 (5.2-8.5 nm) were produced through surfactant assisted sol-gel approach. The emission spectrum confirmed the presence of excited argon, OH, excited nitrogen, excited oxygen, ozone and nitric oxide in the plasma jet. The spectral lines of excited Ar, NO, O3, OH-, N2, [Formula: see text], O, [Formula: see text] and O+ species were observed at wavelength of 695-740 nm, 254.3 nm, 307.9 nm, 302-310 nm, 330-380 nm, 390-415 nm, 715.6 nm, 500-600 nm and 400-500 nm. These reactive species decompose the organic pollutants and separate the heavy metals from the water samples. The conductivity of plasma exposed water samples increased while pH and hardness decreased. The atomic absorption spectrophotometry analysis confirmed the presence of heavy metals in the samples, which were effectively removed through plasma treatment. Finally, the effect of plasma treatment on Staphylococcus aureus strains was more pronounced than Escherichia coli strains.

In-hospital outcomes of patients with chronic kidney disease undergoing percutaneous coronary intervention for chronic total occlusion: a systematic review and meta-analysis.

BACKGROUND: The relative safety and efficacy of percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) in patients with chronic kidney disease (CKD) have not been well defined. We performed a systematic review and meta-analysis of observational studies to assess in-hospital outcomes in this population. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases from inception to April 2020 for all clinical trials and observational studies. Five observational studies with a total of 6769 patients met our inclusion criteria. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR <60 ml/min/1.73m2 in CKD group and ≥ 60 ml/min/1.73m2 in non-CKD group). The primary outcome was in-hospital mortality. Secondary outcomes were acute kidney injury, coronary injury (perforation, dissection or tamponade), stroke and procedural success. Mantel-Haenszel random-effects model was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). RESULTS: In-hospital mortality was significantly higher among patients with CKD undergoing PCI for CTO (OR: 5.16, 95% CI: 2.60-10.26, P < 0.00001). Acute kidney injury (OR: 2.54, 95% CI: 1.89-3.40, P < 0.00001) and major bleeding (OR: 2.58, 95% CI: 1.20-5.54, P < 0.01) were also more common in the CKD group. No significant difference was observed in the occurrence of stroke (OR: 2.36, 95% CI: 0.74-7.54, P < 0.15) or coronary injury (OR: 1.38, 95% CI: 0.98-1.93, P < 0.06) between the two groups. Non-CKD patients had a higher likelihood of procedural success compared to CKD patients (OR: 0.66, 95% CI: 0.57-0.77, P < 0.00001). CONCLUSION: Patients with CKD undergoing PCI for CTO have a significantly higher risk of in-hospital mortality, acute kidney injury and major bleeding when compared to non-CKD patients. They also have a lower procedural success rate.

Happy Hookers: findings from an international study exploring the effects of crochet on wellbeing.

AIMS: With rising rates of mental health disorders being reported globally, it is imperative that we investigate economical and accessible ways to increase relaxation and reduce stress. While there is a plethora of anecdotal evidence as to the positive effects of domestic crafts on mental wellbeing, there is little empirical research in this area. As such, we aimed to explore perceived links between crochet and wellbeing. METHODS: An online survey was developed and piloted, based on an existing tool that explored knitting and wellbeing. The final survey was promoted through social media, over a 6-week period, resulting in valid responses from 8391 individuals. RESULTS: Most respondents were female (99.1%), aged between 41 and 60 years (49.5%) and living in 87 different countries. Many respondents reported crocheting for between 1 and 5 years (42.6%). The three most frequent reasons reported for crocheting were: to be creative (82.1%), to relax (78.5%) and for a sense of accomplishment (75.2%). Respondents reported that crochet made them feel calmer (89.5%), happier (82%) and more useful (74.7%). There was a significant improvement in reported scores for mood before crocheting (M = 4.19, SD = 1.07) and mood after crocheting (M = 5.78, SD = 0.82); z = -69.86, p < .001, r = -0.56. Content analysis of free-text responses identified five major themes: (1) health benefits, (2) process of crochet, (3) personal connection, (4) crochet as contribution and (5) online crochet communities. CONCLUSION: The data suggests that crochet offers positive benefits for personal wellbeing with many respondents actively using crochet to manage mental health conditions and life events such as grief, chronic illness and pain. Crochet is a relatively low-cost, portable activity that can be easily learnt and seems to convey all of the positive benefits provided by knitting. This research suggests that crochet can play a role in promoting positive wellbeing in the general population, adding to the social prescribing evidence base.

Rosuvastatin Use Implicated in the Drug Reaction with Eosinophilia and Systemic Symptoms.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life-threatening drug-induced hypersensitivity reaction that is most closely associated with antiepileptics and antibiotics. While cases of DRESS are rare, here we present a case of DRESS in an adult male following administration of rosuvastatin who presented with fevers, generalized rash, and facial fullness. Vitals on presentation were temperature 102oF, pulse 95/min, blood pressure 95/47 mmHg, and respiratory rate of 14/min. His physical examination revealed scleral icterus, generalized blanching maculopapular rash, facial fullness, and right upper quadrant tenderness. Laboratory investigations found hemoglobin 10 gm/dl, white blood cell count 16.0 K/uL, peripheral eosinophil count 1,700 K/uL, alkaline phosphatase 2,501 U/L, aspartate transaminase 620 U/L, alanine transaminase 680 U/L, total bilirubin 13.2 mg/dl with a direct component of 9 mg/dl, blood urea nitrogen 66 mg/dl, creatinine 5.20 mg/dl, glomerular filtration rate 8 ml/min, and immunoglobulin E level 623 IU/mL. Serology for viral hepatitis, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 was negative. Computed tomographic scan of chest, abdomen, and pelvis showed generalized lymphadenopathy. Over the next week, the patient deteriorated clinically with worsening transaminitis and oliguric acute renal failure requiring renal replacement therapy. As per the European Registry of Severe Cutaneous Adverse Reaction Criteria (RegiSCAR), the probability of rosuvastatin-induced DRESS syndrome was scored as "definite." He was treated with systemic and topical glucocorticoids leading to a gradual improvement in his symptoms. Skin biopsy was suggestive of DRESS syndrome as well. Since DRESS carries such a significant risk of mortality between 10% and 20%, DRESS must be recognized and treated as soon as symptoms present. Clinicians should also be aware that statins, one of the most commonly prescribed drugs, are also a potential cause DRESS.

Pharmacological and Non-pharmacological Strategies for Volume Overload in Acute Decompensated Congestive Heart Failure: A Review Article.

The epithet of acute decompensated heart failure (ADHF) is volume overload. ADHF is associated with a rising number of hospital admission for volume overload. Medication non-compliance, excessive salt intake, comorbidities, and/or disease progression can attribute to volume overload. Heart failure (HF) therapy has innovated during the past few decades, but diuretics have been the mainstay of treatment. Diuretics are vital even though these drugs stimulate the renin-angiotensin-aldosterone system (RAAS) and lead to adaptive responses like diuretic resistance, neurohormonal activation, and worsening renal function that may be inimical. There has been a thriving interest in cutting-edge strategies to manage volume overload in ADHF. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) guidelines advocate pharmacological and non-pharmacological interventions to treat volume overload in ADHF patients. Ultrafiltration (UF) is, therefore, an emerging stand-in therapy of interest for treating volume overload in ADHF patients. This review article epitomizes available clinical data on the use of diuretics and UF in ADHF patients and identifies challenges for each approach.

Incidence, risk factors, treatment, and survival of ovarian metastases of colorectal origin: a Dutch population-based study.

OBJECTIVE: The aim of this nationwide study was to provide insight in the incidence, risk factors, treatment, and survival of patients with ovarian metastases from colorectal cancer (CRC). METHODS: Data from the Netherlands Cancer Registry were used. All newly diagnosed female CRC patients between 2008 and 2016 were included. Treatment was categorized as follows: cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC); resection of the primary tumor; palliative treatment; and no treatment. Overall survival (OS) was investigated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Of 53,883 female CRC patients, 11,343 (21.1%) had metastases at time of diagnosis. Among them, 471 (4.2%) had ovarian metastases. Within latter group, 27.2% received CRS-HIPEC; 38.4% underwent resection of the primary tumor; 25.3% received palliative treatment; and 9.1% received no treatment. Median OS of all patients with ovarian metastases was 17.5 months. In patients receiving CRS-HIPEC, OS was significantly longer than in patients undergoing resection only (median OS 34.1 vs. 17.5 months, adjusted HR 0.44 [0.33-0.66]). Five-year OS was 28.5% for patients having underwent CRS-HIPEC, 11.0% for patients having underwent resection of the primary tumor, 1.2% for patients having underwent palliative treatment, and 0.0% for patients without treatment. CONCLUSIONS: Synchronous ovarian metastases are diagnosed in 4.2% of female colorectal patients presenting with metastatic disease. Risk factors are young age, T4/N+ tumor and histology of signet ring cell carcinoma. Median OS of the entire cohort was 17.5 months, ranging from 3.1 months in patients without treatment to 34.1 months in patients undergoing CRS-HIPEC.