Long-term Management Of Patients Research Articles

Targeting Skeletal Muscle Dysfunction With L-Carnitine for the Treatment of Patients With Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a major medical problem and the world's third leading cause of death. COPD is a chronic disease with heterogeneous clinical symptoms, disease progression, and treatment responses. Besides pulmonary symptomatology, the common systemic clinical manifestations are cachexia, muscle weakness, and widespread comorbidities such as cardiovascular diseases, diabetes, osteoporosis, and infections. The adverse effects of pharmaceutical therapies contribute to the difficulty of health risk assessment and management of COPD patients. This review shows how skeletal muscle dysfunction and metabolic abnormalities contribute significantly to COPD patients' symptoms, functional activities, quality of life, and overall disease outcomes. Based on the clinical evidence of L-carnitine and derivatives as metabolic and muscle bioenergetic enhancers, we propose broader research and implementation of this nutraceutical agent as an effective, inexpensive, and safe adjuvant therapeutic for the long-term management of COPD patients. Moreover, we believe the management of COPD as a chronic disease should be shifted from symptomatic reactive pharmaceutical intervention to more constructive and non-toxic approaches using a single or combination of natural and nutritional agents with potential muscle metabolic enhancing and immunomodulating activities to achieve a better overall outcome for the patients in terms of morbidity, mortality, and medical cost-reduction.

Statin therapy is associated with improved perioperative outcomes and long-term mortality following carotid revascularization in the Vascular Quality Initiative.

Statin therapy is the standard of care for patients with carotid artery stenosis given its proven cardiovascular benefits. However, the impact of statin therapy on outcomes in patients undergoing carotid revascularization in the Vascular Quality Initiative has not yet been evaluated. Therefore, our aim was to investigate the association of statin therapy with outcomes following carotid endarterectomy (CEA), transfemoral carotid artery stenting (tfCAS), and transcarotid artery revascularization (TCAR). We identified all patients who underwent CEA, tfCAS, or TCAR in the Vascular Quality Initiative registry from January 2016 to September 2021. To compare outcomes, we stratified patients by procedure type and created 1:1 propensity score-matched cohorts of patients who received no preoperative statin therapy (within 36hours of procedure) versus those who received preoperative statin therapy. Propensity scores incorporated demographic characteristics, comorbidities, carotid symptom status, preoperative medications, and physician and hospital procedural experience. The primary outcome was a composite end point of in-hospital stroke and/or death. As a secondary analysis, we performed repeat propensity score-matching by postoperative statin use (prescribed at discharge) and assessed 5-year mortality. Relative risks (RR) and hazard ratios (HR) were calculated using log binomial regression and Cox regression, respectively. Among 97,835 CEA, 20,303 tfCAS, and 22,371 TCAR patients, 15%, 17%, and 10% of patients did not receive preoperative statin therapy, respectively. Compared with statin use, no statin use was associated with a higher risk of in-hospital stroke or death among 13,434 matched CEA patients (no statin, 1.7% vs statin, 1.4%; RR, 1.2; 95% confidence interval [CI], 1.02-1.5) and among 2707 matched tfCAS patients (4.8% vs 2.8%; RR, 1.7; 95% CI, 1.3-2.3). However, there was no difference for this outcome by statin use among 2089 matched TCAR patients (1.8% vs 1.6%; RR, 1.1; 95% CI, 0.7-1.8). At5years, no statin therapy at discharge was associated with higher 5-year mortality after CEA (15% vs 10%; HR, 1.8; 95% CI, 1.6-2) and tfCAS (18% vs 14%; HR, 1.5; 95% CI, 1.2-1.8), but there was no difference after TCAR (14% vs 11%; HR, 1.3; 95% CI,0.9-1.8). Compared with statin use, no statin use was associated with a higher risk of in-hospital stroke or death and 5-year mortality among CEA and tfCAS patients. Although there was no significant difference in outcomes among TCAR patients, this may in part be due to lower statistical power in this cohort. Overall, statin therapy is essential in the short- and long-term management of patients undergoing carotid revascularization. Our findings not only support current Society for Vascular Surgery recommendations for statin therapy in patients undergoing carotid revascularization, but they also highlight an important opportunity for quality improvement.

Predictive models for endoscopic disease activity in patients with ulcerative colitis: Practical machine learning-based modeling and interpretation.

Endoscopic disease activity monitoring is important for the long-term management of patients with ulcerative colitis (UC), there is currently no widely accepted non-invasive method that can effectively predict endoscopic disease activity. We aimed to develop and validate machine learning (ML) models for predicting it, which are desired to reduce the frequency of endoscopic examinations and related costs. The patients with a diagnosis of UC in two hospitals from January 2016 to January 2021 were enrolled in this study. Thirty nine clinical and laboratory variables were collected. All patients were divided into four groups based on MES or UCEIS scores. Logistic regression (LR) and four ML algorithms were applied to construct the prediction models. The performance of models was evaluated in terms of accuracy, sensitivity, precision, F1 score, and area under the receiver-operating characteristic curve (AUC). Then Shapley additive explanations (SHAP) was applied to determine the importance of the selected variables and interpret the ML models. A total of 420 patients were entered into the study. Twenty four variables showed statistical differences among the groups. After synthetic minority oversampling technique (SMOTE) oversampling and RFE variables selection, the random forests (RF) model with 23 variables in MES and the extreme gradient boosting (XGBoost) model with 21 variables in USEIS, had the greatest discriminatory ability (AUC = 0.8192 in MES and 0.8006 in UCEIS in the test set). The results obtained from SHAP showed that albumin, rectal bleeding, and CRP/ALB contributed the most to the overall model. In addition, the above three variables had a more balanced contribution to each classification under the MES than the UCEIS according to the SHAP values. This proof-of-concept study demonstrated that the ML model could serve as an effective non-invasive approach to predicting endoscopic disease activity for patients with UC. RF and XGBoost, which were first introduced into data-based endoscopic disease activity prediction, are suitable for the present prediction modeling.

Mid-term follow-up chest CT findings in recovered COVID-19 patients with residual symptoms.

More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups. A total of 407 consecutive COVID-19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest CT study, which was evaluated for specific lung alterations and morphological patterns. The most frequently observed lung CT alterations, in order of frequency, were ground-glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non-specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%). Our work showed that recovered COVID-19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations. This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.

Clinical characteristics of second primary malignancies among first primary malignancy survivors: A single-center study, 2005-2020.

The cancer survivor population is growing due to advances in detection and treatment. For improved long-term patient management, it is critical to examine the clinical characteristics and outcomes of second primary malignancies (SPMs). An SPM is defined as a second distinct pathological diagnosis, with the same or different origin as the first primary malignancy (FPM). In the present retrospective study, categorical clinical variables were compared between subgroups and the impact on overall survival was evaluated. A total of 1,188 patients with an FPM were included, of which 102 experienced an SPM (8.59%). When compared with the patients who did not develop an SPM, patients with an SPM were significantly older at first diagnosis, had a higher pathological stage and higher rates of biliary tract disease and thyroid disease. In addition, patients with an SPM were more likely to have received postoperative chemotherapy (28.43 vs. 12.16%, P<0.0001) and to be long-term consumers of cigarettes and alcohol (25.00 vs. 8.95%, P<0.05). In addition, an increase in the number of regimens received but not in the number of courses of chemotherapy was associated with a reduction in the time interval to SPM development. Non-small cell lung cancer (NSCLC) was the most common type of FPM (18.27%). In patients with NSCLC the occurrence of SPMs was relatively low (5.07%) and the SPM-associated mortality rate was 2.30%. Breast cancer was the second common type of FPM (12.09%). Patients with breast cancer had a relatively high likelihood of developing an SPM (9.30%), for which family history of malignancy and postoperative chemotherapy were identified as potential risk factors. Patients with stomach cancer were the most vulnerable to SPM (17.95%) and patients with digestive tract cancer had the longest time interval between the FPM and SPM development. In addition, thyroid adenoma was identified as a potential risk factor for SCLC. The findings of the present study may provide valuable guidance for the short- and long-term monitoring of FPM survivors.

Loss of muscle mass in women with premature ovarian insufficiency as compared with healthy controls.

Menopausal transition has been known to be associated with the loss of muscle mass. However, muscle health in women with premature menopause, that is, premature ovarian insufficiency (POI), remains unclear. We aimed to investigate and compare muscle mass parameters and the prevalence of low muscle mass between patients with spontaneous POI and healthy controls. In this cross-sectional study, 59 women with spontaneous POI and 57 premenopausal controls with normal ovarian function were enrolled at the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) from June 17, 2020, to August 20, 2021. Muscle mass parameters were measured by dual-energy x-ray absorptiometry, and low muscle mass was diagnosed using the Asian Working Group for Sarcopenia criteria. In addition, participants provided their sociodemographic data, menstrual and reproductive history, lifestyle factors, and medical history. Multivariate linear regression analysis was conducted. Muscle mass parameters, including appendicular skeletal muscle mass (ASM), ASM/height2, ASM/weight, ASM/body mass index, total skeletal muscle mass (TSM), and TSM/weight, were significantly lower in women with POI as compared with healthy controls (ASM: 14.62 ± 2.08 vs 15.97 ± 1.78, P < 0.001; ASM/height2: 5.71 ± 0.64 vs 6.15 ± 0.62, P < 0.001; ASM/weight: 0.27 [0.25, 0.28] vs 0.28 [0.27, 0.29], P = 0.002; ASM/BMI: 0.68 ± 0.07 vs 0.73 ± 0.06, P = 0.001; TSM: 33.85 ± 4.08 vs 36.43 ± 3.56, P < 0.001; TSM/weight: 0.63 [0.59, 0.65] vs 0.64 [0.61, 0.67], P = 0.02). The prevalence of low muscle mass in POI patients was significantly higher than that in controls (32.20% vs 8.77%, χ2 = 9.70, P = 0.002). Furthermore, multivariate linear regression analyses demonstrated that POI status was an independent risk factor for ASM (β = -1.13; 95% CI, -1.62 to -0.65), ASM/height2 (-0.35, -0.47 to -0.22), ASM/weight (-0.01, -0.02 to -0.009), ASM/BMI (-0.05, -0.07 to -0.02), TSM (-2.16, -3.14 to -1.17), and TSM/weight (-0.03, -0.04 to -0.02). Women with POI exhibit significant loss of muscle mass as compared with healthy controls. Early diagnosis and long-term health management in POI patients are important.

The role of primary dental care practitioners in the long-term management of patients treated for head and neck cancer

Patients treated for head and neck cancer may be susceptible to a higher incidence of dental disease due to long-term sequelae of treatment for head and neck cancer. Most patients with head and neck cancer are discharged from a hospital environment and responsibility for long-term dental care is transferred back from the restorative dentistry team to the dentist and dental care professionals in primary care. Treatment of these patients should be undertaken in a supportive environment, taking into account the physical and psychological repercussions of previous treatment. With the exception of some surgical procedures, routine dental care is not contraindicated in patients after head and neck cancer treatment and it is expected that the dentist and dental care professionals will be responsible for long-term routine dental treatment. Primary dental care practitioners should be aware of the process to refer patients back to the head and neck cancer multidisciplinary team if they note a suspicious change during their routine clinical examinations. Referral to a restorative dentistry consultant for planning and carrying out complex items of care may sometimes be necessary, but patients should always remain under the long-term care of their primary dental care practitioner.

Design of Effisayil™ 2: A Randomized, Double-Blind, Placebo-Controlled Study of Spesolimab in Preventing Flares in Patients with Generalized Pustular Psoriasis.

Generalized pustular psoriasis (GPP) is a rare autoinflammatory skin disease characterized by flares of widespread erythema with sterile pustules, and can be relapsing with recurrent flares, or persistent with intermittent flares. Spesolimab, a humanized anti-interleukin-36 (IL-36) receptor monoclonal antibody, targets the key IL-36 pathogenetic pathway in GPP. A previous study showed that spesolimab treatment led to rapid pustular and skin clearance in patients with GPP flares, which was sustained for up to 12weeks. This study investigates the long-term effects of spesolimab on GPP flares, for which no specific treatments are currently available. The Effisayil™ 2 study will assess whether maintenance treatment with subcutaneous spesolimab prevents the occurrence of GPP flares and determine the optimal dosing regimen to achieve this aim. Patients will have a documented history of GPP with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear) at screening and randomization. Patients will be randomized 1:1:1:1 to three groups receiving a 600-mg subcutaneous loading dose of spesolimab followed by a 300-mg maintenance dose administered every 4 or 12weeks, or a 300-mg loading dose followed by a 150-mg maintenance dose administered every 12weeks, and one group receiving placebo, for 48weeks. The primary endpoint is time to first GPP flare. If a patient experiences a GPP flare during the randomized maintenance treatment period, an open-label intravenous dose of 900-mg spesolimab will be administered, with an option for a second intravenous dose after 1week. Effisayil™ 2 is the first placebo-controlled study in patients with GPP to investigate whether maintenance treatment with spesolimab can prevent flares and provide sustained disease control. This study will provide valuable insights on the long-term management of patients with this potentially life-threatening skin disease. NCT04399837.

Long-term Management of Patients with Myocardial Infarction: An Updated Review

The outcomes of patients with myocardial infarction (MI) have substantially improved given the rapid progress that has occurred in revascularization techniques and secondary prevention, and the majority of MI patients subsequently enter a chronic stable phase. Therefore, the long-term management of patients with MI has become a core issue in daily clinical practice for cardiologists. The long-term incidence of adverse events can be further reduced using newly developed medications and therapies ranging from lipid-lowering agents (eg, proprotein convertase subtilisin/kexin type 9 inhibitors) to anti-thrombotic treatments (eg, shortened dual anti-platelet therapy). However, a considerable number of patients still experience adverse events, as some residual risk can remain despite intensive secondary prevention, such as continuously elevated cholesterol levels, chronic cardiovascular inflammation, and rapid atherosclerosis progression due to increased plaque instability. Therefore, the present review sought to summarize and discuss recent advances in several key aspects regarding the long-term management of MI patients, with the expectation of clarifying the available treatment strategies for various clinical scenarios, examining the gaps between trial evidence and clinical practice, and providing possible directions for future research.

LBODP020 Treatment Of Hypercalcemia Due To Prolonged, Excessive Vitamin D Intake

Abstract Case A 66-year-old man with history of anxiety, depression, and complex regional pain syndrome presented to a psychiatric hospital with suicidal ideation. Admission laboratory studies demonstrated hypercalcemia (Ca 14.2 mg/dL) with kidney injury (Cr 3.26). He endorsed taking 5 to 16 (average 8-9) tablets of 1000 IU Vitamin D daily for 10 years. He had heard about the health benefits of Vitamin D and believed it gave him a euphoric effect. Work-up demonstrated elevated ionized calcium (1.63 mmol/L), normal serum phosphorus (3.8 mg/dL), low total protein (6.24 g/dL), normal total albumin (3.42 g/dL), and negative serum protein electrophoresis. Intravenous hydration with normal saline at 200 cc/hr was initiated along with intravenous furosemide. Additional work up demonstrated a suppressed parathyroid hormone level (10pg/ml). 25-hydroxyvitamin D3 (25-(OH)D3) levels were elevated beyond the measurable range (&amp;gt; 155.9 pg/mL). The plasma 1α,25-dihydroxyvitamin D3 (1α,25 (OH)2D3) was normal at 44 pg/mL (range 18-64 pg/mL). With intravenous fluid administration, the patient's ionized calcium level decreased and his creatinine improved. However, 48 hours after the fluids were discontinued on hospital day 3, the ionized calcium and serum creatinine rose once again. Due to the long half-life of Vitamin D and the up-trending calcium levels, he received 60mg of intravenous Pamidronate on hospital day 8. On discharge on hospital day 11, his renal function was stable (Cr 2.24) with normal ionized calcium (1.27 mmol/L). His psychiatric symptoms had resolved. Discussion The two most common causes of hypercalcemia are primary hyperparathyroidism and malignancy. Less commonly, vitamin D-mediated hypercalcemia may result from ectopic 1,25-dihydroxyvitamin D production or excessive Vitamin D ingestion. The known upper limit of daily Vitamin D intake in an adult that will cause no adverse risk is 4000 IU per day. Vitamin D is a fat-soluble vitamin with a half-life of approximately 2 months. The liver converts Vitamin D3 to the metabolite 25-(OH)D3, which has a half-life of 15 days, and the kidney further metabolizes this to 1α,25 (OH)2D3, which has a half-life of 15 hours. Therefore, this patient's 25-(OH)D3 was expected to remain at toxic levels for an unknown time period, placing him at risk of prolonged hypercalcemia with further deterioration of his renal function. There is no standard of care established for patients with vitamin D toxicity. Pamidronate, normally contraindicated for GFR &amp;lt;30 mL/min, was administered after nephrology consultation. Information about vitamin D toxicity is primarily gleaned from case reports and series. This case report serves as a model for study of Vitamin D toxicity in humans for understanding the long-term management in patients with chronic vitamin D toxicosis presenting with renal failure. Presentation: No date and time listed

Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis.

Strategies on long-term management of patients affected by atopic dermatitis (AD) undergoing treatment with dupilumab achieving good clinical response (GCR) or experiencing dupilumab-related adverse events (AEs) are scant. Data of patients who implemented longer than scheduled dupilumab dosing interval due to GCR (at least 52 weeks of treatment and controlled AD activity [Eczema Area Severity Index ≤7 and Dermatology Life Quality Index ≤5 for at least 6months]) or AEs (dupilumab-related and treatment-resistant conjunctivitis) were retrospectively collected. Dupilumab was tapered to Q3W or Q4W based on physician-patient shared decision. At baseline (T0) and each follow-up (week 16 [T1] and week 32 [T2]) disease severity was assessed. A total of 59 patients implemented longer than scheduled dosing interval (44 GCR, 15 AEs). Among these, 50 (35 GCR and 15 conjunctivitis) patients switched to 300 mg Q3W, while nine GCR subjects to Q4W. In the GCR group Q3W, 34 and 31 patients maintained clinical response at T1 and T2, whereas eight and seven Q4W subjects maintained clinical response at the same timepoints, respectively. No significant differences in AD severity were observed between T1 and T2 in both groups. Contrariwise, one Q3W and one Q4W patients at T1, and three Q3W and one Q4W subjects at T2, returned to dupilumab labeled dosage due to AD worsening. In conjunctivitis group, dupilumab Q3W was maintained in eight and four patients at T1 and T2, respectively. Three patients at T1 and three at T2 subjects returned to the labeled interval due to conjunctivitis remission. Four patients at T1 and four subjects at T2 interrupted dupilumab due to the persistence of conjunctivitis. A longer dupilumab dosing interval may be a valuable option in patients with a GCR and may be a useful strategy to reduce treatment-related conjunctivitis, also with pharmacoeconomic benefit.

Neurosarcoidosis: Phenotypes, Approach to Diagnosis and Treatment.

The aim of this review is to provide an update of clinical presentation, diagnosis, differential diagnoses, and treatment according to recent evidence. Neurosarcoidosis remains a diagnosis of exclusion, with infectious and malignant etiologies recognized as important mimickers. Corticosteroids remain as first-line therapy. In recent years, however, studies have demonstrated the effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in the treatment of neurosarcoidosis, leading to improved outcomes. Neurosarcoidosis is a granulomatous disease with protean manifestations that may affect any part of the central and peripheral nervous system. It has many mimickers, and potentially devastating complications necessitating long-term follow-up. Early initiation of treatment, particularly with anti-TNF therapy, may lead to better outcomes and fewer relapses. There is an unmet need for randomized controlled trials that provide robust data to guide therapy and the long-term management of neurosarcoidosis patients.

Developing and validating a prognostic model for mortality in patients with heart failure

Abstract Background Heart Failure (HF) constitutes a major public health problem which remains highly prevalent in the UK and globally. Primary care plays a role in the long-term management of patients with heart failure but there are no clinically useful prognostic models to guide primary care professionals in determining those at increased risk of mortality, who could benefit from appropriate advanced care planning or escalation of treatment. Several predictive models exist but due to several limitations, clinical utility of these in the UK are limited. Purpose This study developed and validated a prognostic algorithm, the Nottingham Heart Failure Model, to predict the one-year risk of all-cause mortality in patients with HF. Methods This was a retrospective open cohort study using electronic primary care records from the UK Clinical Practice Research Datalink (CPRD) linked with secondary care records from Hospital Episode Statistics (HES) and death registration data from the Office for National Statistics (ONS). Adults with a diagnosis of heart failure were identified and multivariable Cox regression models were used to identify the risk factors that were independently associated with mortality. A prognostic model was developed to predict the one-year risk of mortality in patients with heart failure, and this was validated by bootstrapping 200 samples of the derivation data. The cohort was then split into even quartiles based on predicted risk scores from the model. These risk groups ranged from one to four with one indicating the quartile of scores with the lowest risk. Kaplan Meier curves were then produced for each group. The Royston D-statistic was then used to assess the discrimination of these quartiles by quantifying the observed separation between these groups. Results A total of 109,577 patients with diagnoses of heart failure were followed up from 1 January 2000 to 31 December. There were 16,437 deaths during the period of follow up. We identified 29 factors which were significantly associated with mortality risk and a prognostic model which incorporated these factors, was developed. The resulting prognostic model obtained a model validation score (C-statistic) of 0.79. The agreement between the observed and predicted proportion of events showed excellent apparent calibration. The D statistic of 1.65 suggests that the model provides a reasonably high amount of prognostic separation. Conclusion(s) Several patient characteristics including comorbidities, treatments, and biomarkers are significantly associated with heart failure mortality. This new model has the potential to accurately predict heart failure mortality within one year and will enable primary care professionals to better risk stratify their patients with heart failure. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Aziz Foundation

Two-year quality of life after acute pulmonary embolism: results from the FOCUS study

Abstract Background/Introduction No firm prospective evidence exists on the long-term course of disease-specific and generic quality of life (QoL) or their determinants in patients with acute pulmonary embolism (PE). Reliable data on this topic is essential for early identification of patients at risk of deviating from the expected course and prevention of clinical events affecting QoL recovery after PE. Purpose We examined the two-year course of QoL and the impact of events occurring after the acute phase of PE in patients from the prospective multicentre FOllow-up after aCUte pulmonary emboliSm (FOCUS) study. Methods All patients with complete QoL assessment at 3, 12 and 24 months (N=462) were included in the analysis of the two-year course of QoL; all patients with QoL assessment at 12 months, 24 months, or both (N=740) contributed to a multivariable linear mixed-effects regression for the investigation of determinants of long-term QoL. Disease-specific QoL was assessed with the Pulmonary Embolism Quality of Life (PEmb-QoL) instrument (global score: 0 = best, 100 = worst QoL), generic health-related QoL with the Euro Quality of life group (EuroQol) five-dimensions utility index (EQ-5D-5L; 0 = worst, 1 = best QoL) and the EuroQol visual analogue scale (0 = worst, 100 = best QoL). Incident events (recurrent PE, bleeding, stroke, new cancer diagnosis, and re-hospitalization) were modelled as time-varying covariates from discharge to month 12 and from month 12 to month 24. Results Among 462 patients with complete QoL assessment [200 (43.3%) women, median age 61.5 (IQR: 49–72) years, high-risk PE 15/462 (3.2%)], the median (IQR) PEmb-QoL score at 3, 12, and 24 months was 20 (9–36), 14 (5–30) and 13 (5–28), with a similar trend across all sub-dimensions (Figure 1); the mean (95% CI) EQ-5D-5L utility index 0.86 (0.84–0.88), 0.88 (0.87–0.90) and 0.87 (0.85–0.89); the mean (95% CI) EuroQoL visual analogue scale 74.2 (72.5–75.9), 76.8 (75.2–78.4) and 76.3 (74.6–78.0). Upon multivariable analysis in 740 patients with QoL data at 12 or 24 months, QoL according to all three scales was worse in women, patients of older age, with cardiopulmonary disease, with higher BMI, and in smokers, but did not change significantly at 24 vs 12 months. Incident PE recurrence or stroke did not considerably affect any of the QoL dimensions, whereas re-hospitalization for any cause worsened disease-specific QoL, a new cancer diagnosis worsened both scales of generic QoL, and bleeding worsened generic QoL as assessed by the Visual Analogue Scale (Table 1). Conclusion Generic and disease-specific QoL after PE improved in the first year and then plateaued in the second year. Disease-specific QoL was adversely affected by re-hospitalization for any cause but was robust to new cancer diagnosis and bleedings, which instead worsened generic QoL. These findings may support long-term management of patients with PE and contribute to design and interpretation of interventional studies. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Health Care

Italian Society of Cardiology-Italian Society of Nephrology Consensus document: The cardio-renal interaction in the prevention and treatment of cardiovascular diseases - Part II: From preventive strategies to treatment of patients with cardio-renal damage

Chronic kidney disease and cardiovascular disease are strictly connected each other with a bidirectional interaction. Thus, the prevention of cardio-renal damage, as its appropriate treatment, are essential steps for a correct management of long-term patients' prognosis. Several preventive and therapeutic strategies, pharmacological and not, are now available for cardio-renal damage prevention and treatment, and for the management of its complications. The second part of this consensus document focuses on the management and treatment of cardio-renal damage, directing the attention on the correct use of drugs that may slow renal disease progression, on the application of preventive strategies in case of invasive cardiac procedures with the use of contrast agents, and on the accurate use of cardiological drugs in patients with chronic kidney disease.

Pharmacological, Nutritional, and Rehabilitative Interventions to Improve the Complex Management of Osteoporosis in Patients with Chronic Obstructive Pulmonary Disease: A Narrative Review.

Osteoporosis is a highly prevalent condition affecting a growing number of patients affected by chronic obstructive pulmonary disease (COPD), with crucial implications for risk of fragility fractures, hospitalization, and mortality. Several risk factors have been identified to have a role in osteoporosis development in COPD patients, including corticosteroid therapy, systemic inflammation, smoke, physical activity levels, malnutrition, and sarcopenia. In this scenario, a personalized multitarget intervention focusing on the pathological mechanisms underpinning osteoporosis is mandatory to improve bone health in these frail patients. Specifically, physical exercise, nutritional approach, dietary supplements, and smoke cessation are the cornerstone of the lifestyle approach to osteoporosis in COPD patients, improving not only bone health but also physical performance and balance. On the other hand, pharmacological treatment should be considered for both the prevention and treatment of osteoporosis in patients at higher risk of fragility fractures. Despite these considerations, several barriers still affect the integration of a personalized approach to managing osteoporosis in COPD patients. However, digital innovation solutions and telemedicine might have a role in optimizing sustainable networking between hospital assistance and community settings to improve bone health and reduce sanitary costs of the long-term management of COPD patients with osteoporosis.

Identification and Validation of a Prognostic Signature Based on Methylation Profiles and Methylation-Driven Gene DAB2 as a Prognostic Biomarker in Differentiated Thyroid Carcinoma.

Recurrence is the major death cause of differentiated thyroid carcinoma (DTC), and a better understanding of recurrence risk at early stage may lead to make the optimal medical decision to improve patients' prognosis. The 2015 American Thyroid Association (ATA) risk stratification system primary based on clinic-pathologic features is the most commonly used to describe the initial risk of persistent/recurrent disease. Besides, multiple prognostics models based on multigenes expression profiles have been developed to predict the recurrence risk of DTC patients. Recent evidences indicated that aberrant DNA methylation is involved in the initiation and progression of DTC and can be useful biomarkers for clinical diagnosis and prognosis prediction of DTC. Therefore, there is a need for integrating gene methylation feature to assess the recurrence risk of DTC. Gene methylation profile from The Cancer Genome Atlas (TCGA) was used to construct a recurrence risk model of DTC by successively performed univariate Cox regression, LASSO regression, and multivariate Cox regression. Two Gene Expression Omnibus (GEO) methylation cohorts of DTC were utilized to validate the predictive value of the methylation profiles model as external cohort by receiver operating characteristic (ROC) curve and survival analysis. Besides, CCK-8, colony-formation assay, transwell, and scratch-wound assay were used to investigate the biological significance of critical gene in the model. In our study, we constructed and validated a prognostic signature based on methylation profiles of SPTA1, APCS, and DAB2 and constructed a nomogram based on the methylation-related model, age, and AJCC_T stage that could provide evidence for the long-term treatment and management of DTC patients. Besides, in vitro experiments showed that DAB2 inhibited proliferation, colony-formation, and migration of BCPAP cells and the gene set enrichment analysis and immune infiltration analysis showed that DAB2 may promote antitumor immunity in DTC. In conclusion, promoter hypermethylation and loss expression of DAB2 in DTC may be a biomarker of unfavorable prognosis and poor response to immune therapy.

Surgeon’s decision concerning limb amputation after frostbite as a basis of subsequent successful activity of general practitioner-family physician (own clinical observations and experience of education in state and English language)

The degree of frostbite depends on environment temperature, cold wind and the duration of exposition. Tissue freezing after the loss of warmth and appearing of ice crystals in superficial and deep tissues are in the basis of frostbite. Because of easy access and peripheral anatomic features frostbites preferably involve distant upper and lower parts of limbs, ears, nose and cheeks. There are wide spectrum of clinical manifestations of frostbites in the range of lesions, which disappear to lesions, which require amputations. Such classification of lesions clinical characteristics is a working classification basing on degree of injury. Even without tissue losses patients may suffer of long-term consequences after frostbites, which can include vasomotor disorders, neuropathic and nociceptive pain and arthritis after frostbites. Article describes own clinical observations of very severe (ending with amputation) frostbite case. We consider submitted description as an informative for discussion during practical classes in state and English languages. Making in time and saving amputation by the surgeon is a very important aspect for the long-term management of patient by primary care physician following rehabilitation program including all necessary vital prescriptions. Described approach to our patient was based on long-term development of manifestations with precise demarcation line and joining of purulent process after frostbite up to the time of his conscious appeal for medical help.

Myocardial infarction with nonobstructive coronary arteries: the need for precision medicine.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) represents about 6-8% of all patients with myocardial infarction (MI), and several pathophysiological mechanisms showed to be involved in this heterogeneous clinical condition. Of note, MINOCA proved to be associated with a significant risk of mortality, angina burden and socioeconomic costs. Results from randomized clinical trials evaluating the clinical effectiveness of a comprehensive diagnostic algorithm, along with the acute and long-term management of patients with MINOCA, are pending. In this review article, we aim at providing an overview of the clinical features, diagnostic work-up and the therapeutic management of patients presenting with MINOCA, highlighting the recent acquisition along with the remaining important knowledge gaps in this field.

A mixed-methods systematic review of nurse-led interventions for people with multimorbidity.

To identify types of nurse-led interventions for multimorbidity and which outcomes are positively affected by them. Mixed-methods systematic review following the Joanna Briggs Institute (JBI) methods for convergent-integrated reviews. CRD42020197956. Cochrane CENTRAL, CINAHL, Embase and MEDLINE were searched in October 2020. Grey literature sources included OpenGrey, the Journal of Multimorbidity and Comorbidity and reference mining. English-language reports of nurse-led interventions for people with multimorbidity were included based on author consensus. Two reviewers performed independent quality appraisal using JBI tools. Data were extracted and synthesized using a pre-existing taxonomy of interventions and core outcome set. Twenty studies were included, with a median summary quality score of 77.5%. Interventions were mostly case-management or transitional care interventions, with nurses in advanced practice, support to self-manage conditions, and an emphasis on continuity of care featuring frequently. Patient-centred outcomes such as quality of healthcare and health-related quality of life were mostly improved, with mixed effects on healthcare utilization, costs, mortality and other outcomes. Interventions such as case management are agreeable to patients and transitional care interventions may have a small positive impact on healthcare utilization. Interventions include long-term patient management or short-term interventions targeted at high-risk junctures. These interventions feature nurses in advanced practice developing care plans in partnership with patients, to simplify and improve the quality of care both in the long and short-term. This is the first mixed-methods review which includes all types of nurse-led interventions for multimorbidity and does not focus on specific comorbidities or elderly/frail populations. Using adapted consensus-developed frameworks for interventions and outcomes, we have identified the common features of interventions and their overall typology. We suggest these interventions are of value to patients and healthcare systems but require localization and granular evaluation of their components to maximize potential benefits.