Poor Clinical Condition Research Articles

STATIN TREATMENT REDUCES THE RISK OF DEATH AMONG ELDERLY FRAIL PATIENTS. EVIDENCE FROM A LARGE POPULATION-BASED COHORT

Objective: Randomized controlled trials show that statin treatment is associated with a reduction of cardiovascular outcomes and mortality. Evidence is limited, however, on whether these drugs are protective in frail patients. Aim of our study was to assess the protective effect of these drugs in a large and unselected cohort of frail elderly subjects. Protection was inferred from the reduction of mortality associated with adherence to treatment because of the evidence that adherence to statin is closely related with outcomes. Design and method: The target population included Lombardy residents (Italy), aged 65 years or older, who received at least three consecutive prescriptions of a statin during 2011–2012. A case-control study was performed, the cases being the cohort members who died until 2018. Logistic regression was used to model the outcome risk associated with statin adherence. Adherence was measured by the proportion of the follow-up covered by prescriptions. The analysis was stratified according to four clinical categories (good, medium, poor, and very poor clinical status), based on different life expectancies, as assessed by a prognostic score (i.e., the Multisource Comorbidity Score) which had been found to sensitively predict the risk of death. From the good to the very poor clinical status, the 7-year death probability increased from 11% to 52%. Results: In each clinical status, there was a significant reduction of all-cause mortality as adherence to statin treatment increased. The reduction in the adjusted risk of mortality from the lowest to the highest adherence level was greatest among patients with a good clinical status (-56%) and less among other cohort members (i.e., -48%, -44% and -47% in medium, poor and very poor groups, respectively). Similar findings were obtained for the risk of cardiovascular mortality. Conclusions: In a real-life setting, adherence to statin treatment reduced the risk of death in elderly patients regardless their clinical conditions. The reduction extended to patients with a high risk of mortality, suggesting that also frail patients are protected by lipid-lowering treatment. However, in these patients the benefit from the treatment seems lower than those in good clinical conditions.

Baseline CHA 2 DS 2 ‐VASc score and prognosis in octogenarians with non‐ST segment elevation acute coronary syndrome

CHA2 DS2 -VASc Score is widely used to predict thromboembolic risk in patients with Atrial Fibrillation (AF). We sought to study if this score predicts outcomes in elderly patients with Non-ST segment Elevation Acute Coronary Syndromes (NSTEACS). The multicenter LONGEVO-SCA prospective registry included 532 unselected patients with NSTEACS aged ≥80 years. Data to calculate CHA2DS2-VASc Score were available in 523 patients (98.3%). They were classified according to CHA2DS2-VASc Score: group 1 (score ≤4), and 2 (5-9). We studied outcomes in terms of mortality or readmission at 6 months follow-up. A total of 266 patients (51%) had a high CHA2DS2-VASc Score (group 2). They were more often women, with more cardiovascular risk factors like hypertension or diabetes mellitus, and history of previous stroke and cardiovascular disease and heart failure (all, p=0.001). Geriatric syndromes (Barthel Index, Lawton Brody, cognitive impairment and frailty) and Charlson index were worse in this group (all, p=0.001). They had poorer clinical status on admission, with worse Killip class and lower left ventricle ejection fraction (all, p=0.001), and developed new onset AF more often during admission (12.4% vs. 6.6%, p=0,024). At six months follow-up, patients in group 2 had higher reinfarction, all-cause mortality, and mortality or readmission rates. A CHA2DS2-VASc Score >4 was associated with mortality or readmission at 6 months (HR 2.07, p<0.001). However, after adjusting for potential confounders, this last association was not significant (p=0.175). A CHA2DS2-VASc score >4 is present in half of octogenarians with NSTEACS and is associated with poorer outcomes. However, it is not an independent predictor of events and should not replace recommended tools for risk prediction in this setting.

Local Anesthetic-Induced Central Nervous System Toxicity during Interscalene Brachial Plexus Block: A Case Series Study of Three Patients.

Local anesthetics are commonly administered by nuchal infiltration to provide a temporary interscalene brachial plexus block (ISB) in a surgical setting. Although less commonly reported, local anesthetics can induce central nervous system toxicity. In this case study, we present three patients with acute central nervous system toxicity induced by local anesthetics applied during ISB with emphasis on neurological symptoms, key neuroradiological findings and functional outcome. Medical history, clinical and imaging findings, and outcome of three patients with local anesthetic-induced toxic left hemisphere syndrome during left ISB were analyzed. All patients were admitted to our neurological intensive care unit between November 2016 and September 2019. All three patients presented in poor clinical condition with impaired consciousness and left hemisphere syndrome. Electroencephalography revealed slow wave activity in the affected hemisphere of all patients. Seizure activity with progression to status epilepticus was observed in one patient. In two out of three patients, cortical FLAIR hyperintensities and restricted diffusion in the territory of the left internal carotid artery were observed in magnetic resonance imaging. Assessment of neurological severity scores revealed spontaneous partial reversibility of neurological symptoms. Local anesthetic-induced CNS toxicity during ISB can lead to severe neurological impairment and anatomically variable cerebral lesions.

Determinants of Opportunistic Infections Among HIV-Positive Patients on HAART in Debre Berhan Referral Hospital, North Shoa Zone, Ethiopia, 2020: A Case-Control Study.

IntroductionOpportunistic infections are an illness that exists more frequently and is more severe in people with HIV. In HIV/AIDS patients, opportunistic infections still cause morbidity and mortality even after the era of highly active antiretroviral therapy (HAART) and most patients die as direct or indirect complications of opportunistic infections. This study was aimed to identify the determinants for the occurrence of opportunistic infections in HIV-positive patients having HAART follow-up in DBRH, Debre Berhan, Ethiopia.MethodsA total of 339 study subjects were involved under institution-based unmatched case–control study design and simple random sampling technique. A pre-tested structured questionnaire was used for data collection. Data were entered using Epidata version 3.1 and analyzed for descriptive and logistic regression models by SPSS version 21. A P-value of less than 0.05 was considered as statistically significant.ResultsAfter adjusting potential confounders, drinking alcohol (AOR=3.12, 95% CI: 1.07–9.06), BMI <18.5 (AOR= 3.36, 95% CI: 1.49–7.55), previous history of opportunistic infections (AOR= 2.96, 95% CI: 1.51–5.8) were independent predictors of opportunistic infections in people living with HIV/AIDS on HAART.ConclusionIn this study, the poor clinical and biochemical status, and behavioral factors were being the predictors of the occurrence of opportunistic infections. HIV/AIDS patients must be assessed and screened for opportunistic infections.

Circulatory dipeptidyl peptidase 3 (cDPP3) is a potential biomarker for early detection of secondary brain injury after aneurysmal subarachnoid hemorrhage

IntroductionDelayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH. Materials and methodscDPP3 levels were quantified in serum obtained from 96 confirmed aSAH patients during the early (EP: d1–4), critical (CP: d5–8, d9–12, d13–15) and late (LP: d16–21) phase after aSAH onset. Associations between cDPP3 levels and demographic or clinical parameters were evaluated. The relations between cDPP3 levels and DCI, DCI-related infarctions and long-term clinical outcomes were examined by receiver operating characteristics (ROC) curve analysis and multivariate logistic regression. ResultsSignificantly higher cDPP3 levels during CP (d5–8, d9–12, d13–15) were observed in patients with poor clinical (p < 0.001 to p = 0.033) or radiological (p = 0.012 to p = 0.039) status on admission, DCI (p < 0.001 to p = 0.001), DCI-related infarctions (p = 0.002 to p = 0.007), and poorer long-term outcome (p = 0.007 to p = 0.019). ROC curve analysis indicated that higher cDPP3 levels on d5–8 are predictive for a poor clinical outcome (area under the curve = 0.677, p = 0.007). In multivariate analysis, there was an independent association between cDPP3 levels on d5–8 and development of DCI-related infarctions (p = 0.038). ConclusionOur results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients.

Endovascular Treatment of Ruptured Wide-Necked Anterior Communicating Artery Aneurysms Using a Low-Profile Visualized Intraluminal Support (LVIS) Device.

Objective: To evaluate the safety and efficacy of low-profile visualized intraluminal support (LVIS) stent-assisted coiling for the treatment of ruptured wide-necked anterior communicating artery (ACoA) aneurysms.Methods: The clinical and angiographic data of 31 acutely ruptured wide-necked ACoA aneurysms treated with LVIS stent-assisted coiling between January 2014 and December 2018 were retrospectively reviewed.Results: All stents were successfully deployed. The immediate angiographic results were modified Raymond-Roy class I in 27 cases, modified Raymond-Roy class II in 2 cases, and modified Raymond-Roy class IIIa in 2 cases. Intraoperative thrombosis and postoperative aneurysmal rebleeding occurred in one case each. Two patients (6.5%) who were admitted due to poor clinical grade conditions died during hospital admission as a result of initial bleeding. Angiographic follow-up (mean: 12.9 months) was performed for 26 patients, the results of which demonstrated that 25 aneurysms were completely occluded and one was class II. The last clinical follow-up (mean: 25.3 months) outcomes demonstrated that 27 patients had favorable clinical outcomes and two had poor clinical outcomes.Conclusion: LVIS stent-assisted coiling for ruptured wide-necked ACoA aneurysms was safe and effective, with a relatively low rate of perioperative complications and a high rate of complete occlusion at follow-up.

Health Economic Aspects of Aneurysmal Subarachnoid Hemorrhage: Factors Determining First Year In-Hospital Treatment Expenses.

Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a common neurosurgical emergency with a high case fatality rate. The clinical course of SAH generates high health economic expenses. Here we highlight possible cost-driving factors for in-hospital care expenses for the first year. Furthermore, results are compared with ischemic stroke treatment. One hundred and one patients with aneurysmal SAH treated in our hospital from 2007 through 2009 were included. The Hunt and Hess (HH) scale, World Federation of Neurosurgical Societies (WFNS) scale, Fisher Scale, and further outcome-relevant data were recorded. Expenses were calculated using the German fixed case rate classification system consisting of Diagnosis-Related Groups (DRG) and the Operation and Procedure catalogue (OPS). Overall acute length of stay (LOS) and LOS on the intensive care unit (ICU) were separately evaluated. Expenses were compared with formerly published first-year costs of ischemic stroke. Fifty-four percent of the patients (median age 52 years, 69% females) received coiling and 46% clipping. Acute in-hospital treatment accounted for 82% of total in-hospital expenses, while consequential in-hospital treatment accounted only for 18%. Altogether, the total first-year in-hospital expenses for all patients were as high as €2,650,002, resulting in average SAH in-hospital treatment expenses of €26,238 per patient for the first year. Poor clinical condition on admission and longer stay in ICU are the main cost-driving factors. The impact of the aneurysm treatment method is debatable. Only a poor HH grade and longer ICU stay are independent cost-driving factors. SAH treatment expenses are far higher than treatment costs for ischemic stroke in the literature (€6,731 for first-year inpatient and €3,287 for outpatient treatment). Clinical condition and LOS determine in-hospital expenses after SAH. Aneurysmal SAH prevalently results in a relevant economic impact on the health system exceeding formerly published treatment expenses for ischemic stroke.

Focal Peripheral Neuropathy Associated with Lymphoma in Dogs

Background: Peripheral neuropathies result in sensory, motor or autonomic dysfunctions due to impairment of peripheral spinal or cranial nerves. Neoplasms such as lymphoma are cited as one of the many aetiological causes and it may affect the nerve directly, by compression, or indirectly, or paraneoplastic, by remote action of the neoplasm located in an extra-neural site. This study aimed to report two cases of cranial nerve neuropathy (trigeminal and facial) associated with canine lymphoma, contributing to a better understanding of its paraneoplastic effects on the nervous system, as well as the diagnosis and treatment of these conditions.Cases: Two cases of canine lymphoma associated with possible signs of paraneoplastic peripheral neuropathy were attended at the Veterinary Hospital from the Universidade Federal de Minas Gerais (HV UFMG). Case 1. A spayed mixed breed bitch, with lethargy and unilateral exophthalmos. Brain computed tomography revealed a retrobulbar mass and cytology was diagnostic for extranodal lymphoma. Subsequent to computed tomography, the dog was presented with hypotrophy of the facial musculature and difficulty in grasping food, consistent with trigeminal nerve palsy, which resolved after institution of the 19-week chemotherapy protocol from the University of Wisconsin. Nevertheless, disease reccurred and a rescue protocol was initiated. Case 2. A female Dalmatian, spayed, was diagnosed with multicentric lymphoma, after cytology of the left mandibular lymph node. Chemotherapy was initiated with the same protocol of the previous case. However, the disease progressed and it was observed facial asymmetry with ptosis of the left eyelid, pina and lips, in addition to difficulty in grasping food, suggesting facial and trigeminal cranial nerve palsy. Clinical signs resolved after institution of a rescue chemotherapy protocol. However, in both cases, disease progression and poor clinical condition resulted in decision of euthanasia and necropsy was not authorized.Discussion: Canine lymphoma is often associated with paraneoplastic syndromes, with neuropathy being one of its possible clinical manifestations. In spite of that its pathogenesis remains unclear, with little information in the veterinary literature. Diagnosis is challenging and must be initially based on recognition of neurological clinical signs and lesion localization, as in the reported cases with lesions located on the fifth and seventh cranial nerves. In the patient from the first case, the absence of clinical signs and laboratory abnormalities suggestive of endocrinopathies, associated with neurological signs restricted to the trigeminal nerve, bilaterally, before starting chemotherapy and without the identification of brain lesions in computed tomography, suggested paraneoplastic involvement as the cause of neuropathy. In the second case described, the absence of clinical signs and laboratory abnormalitiess suggestive of endocrinopathies or nutritional deficiencies, associated with neurological signs restricted to the facial and trigeminal cranial nerves, suggested direct or indirect tumour involvement. Both cases showed improvement of neurological clinical signs after chemotherapy which favored the therapeutic diagnosis. Nevertheless, failure to authorize necropsy of patients made it impossible to confirm that peripheral neuropathy is secondary to the remote effect of lymphoma.

LOPH and D-MHC in the Treatment of FeLV Associated Acute Leukemia in a Cat

Background: Bone marrow primary malignancies are denominated leukemias, classified as myeloid or lymphoid, according to the cell lineage, and acute or chronic, according to the cell´s state of maturation. In cats, acute lymphoid leukemia is the most common form, especially in regions endemic for feline leukemia virus and / or feline immunodeficiency virus. A new treatment protocol for lymphomas, called LOPH, has been described for animals with FeLV persistent viremia. This study aimed to report a case of a cat presenting with FeLV associated acute leukemia and treated with the LOPH protocol, and, in the rescue phase, a modification of the D-MAC protocol, denominated D-MHC.Case: A 4-year-old mixed breed intact queen was attended due to lethargy and inappetence. The patient did not present any relevant abnormalities in the clinical exam and complementary exams were performed including complete blood count, biochemical profile, SNAP Feline Triple Test, chest radiographs and abdominal ultrasound. Imaging tests and biochemical values were unremarkable, but the patient presented a reagent result for FeLV and severe leukocytosis due to lymphocytosis. The morphological evaluation of the blood smear revealed the presence of blasts, in a concentration greater than 20% of the nucleated cells, which allowed the characterization of a leukemic state, probably lymphoid. First-line treatment was based on the LOPH protocol, including Lomustine, Vincristine, Prednisoloneand Doxorubicin, in four-week cycles. Nevertheless, during the third cycle, 66 days after the institution of this protocol, the patient presented a febrile condition along with marked leukocytosis due to lymphocytosis, confirming leukemia recurrence. A rescue attempt was performed with a modification of the D-MAC protocol, originally consisting of the combination of dexamethasone, melphalan, actinomycin-D and cytarabine, but with replacement of actinomycin-D by doxorubicin, and therefore nominated D-MHC. After the three cycles there was a return of the febrile condition associated with severe pancytopenia and euthanasia was elected due to poor clinical condition, resulting in a survival time of 124 days. The hematological toxicity of the induction protocol included anemia and neutropenia, with mainly grade I events, but with the occurrence of a grade IV event. The adverse effects of the rescue protocol were similar, but with a greater number of grade IV events.Discussion: FeLV is considered the most lethal retrovirus of the domestic cat, with a major impact on health and life expectancy. Persistent FeLV antigenemia increases the risk of hematopoietic neoplasms in 62.1 times due to a direct insertional mutagenesis. In endemic regions, approximately 70% of cats with acute leukemia have persistent FeLV antigenemia, as the patient in this report. The diagnosis was made through association of retroviral status and the identification of more than 20% of blasts, possibly lymphoblasts, in the blood stream, sparing the need for a myelogram. Considering the poor prognosis for acute lymphoid leukemias and the patient's retroviral status, treatment was initiated with the LOPH protocol, including lomustine, as a potent agent to induce remission, and doxorubicin, which can result in longer remission intervals. After 66 days free of the disease, the patient presented recurrence of the leukemic condition, starting the rescue protocol D-MHC. Remission was again obtained with duration similar to the first protocol, however, on the occasion of a new leukemia recurrence, euthanasia was elected. The treatment adopted for the patient in this report resulted in a longer survival time than reported in other studies. Despite the aggressiveness of the protocols, especially the D-MHC, it was possible to perform it using the monocyte and granulocyte stimulation factor to reverse neutropenia.

Vitamin K deficiency-induced spontaneous haemopericardium and cardiac tamponade in an infant with alpha-1 antitrypsin deficiency: a case report.

Background Vitamin K deficiency bleeding is a life-threatening complication in early infancy. Exclusive breastfeeding and neonatal cholestasis syndromes, most notable α-1-antitrypsin deficiency, have been reported to be risk factors. Intracranial haemorrhage is most common. No association to haemopericardium has been reported before.Case summary We report on an 11 weeks old at term-born infant, who presented with severe anaemia and signs of cardiogenic shock. Immediately echocardiography was done and depicted cardiac tamponade. Pericardiocentesis was performed and a significant amount of haemorrhagic fluid was removed. Further workup revealed deranged coagulation parameters, cholestatic liver disease, and reduced α-1-antitrypsin levels. Despite normal brain sonography, a small cerebral haemorrhage was detected on magnetic resonance imaging. A genetic test finally proofed homozygotic mutation of the SERPINA1-gene and confirmed the diagnosis of α-1-antitrypsin deficiency as the underlaying cause. After initial replacement of coagulation factors, erythrocytes and vitamin K, the infant recovered. Eighteen weeks after discharge, the infant is still on vitamin K supplementation. She did not have any further bleedings and no neurologic or developmental impairment.Discussion Alpha-1-antitrypsin deficiency can lead to vitamin K deficiency in young infants even with adequate prophylaxis. Spontaneous haemorrhagic pericardial effusion was a new manifestation of vitamin K deficiency bleeding in our patient and should be considered and ruled out in young infants who present with acute anaemia and poor clinical condition.

Brain Arteriovenous Malformations: Impact of Neurologic Status, Bleeding, and Type of Treatment on Final Outcome

Well-designed studies assessing the treatment outcome of brain arteriovenous malformations (AVMs) are infrequent and have not consistently included all of the available treatment modalities, making their results not completely generalizable. Moreover, the predictors of poor outcome are not well defined. We performed an observational retrospective study of AVM patients. We included patients with clinical, radiologic, and outcome data, with a minimum follow-up of 1 year. Neurologic outcome was documented using the modified Rankin Scale (mRS) at the AVM diagnosis and 30 days after the treatment. There were 117 patients, with equal male/female proportion. The mean follow-up time was 51 months. Treatment distribution in the Spetzler-Martin grades I-III was as follows: 52 (54.6%) surgery, 31 (32.35%) radiosurgery, 2 (0.02%) embolization, and 11 (12%) conservative follow-up. Treatment distribution in Spetzler-Martin grades IV and V was as follows: 4 (20%) surgery, 7 (35%) radiosurgery, and 10 (45%) conservative follow-up. Poor neurologic outcome (mRS ≥ 3) was significantly associated with poor clinical status at diagnosis (Glasgow Coma Scale [GCS] score< 14; odds ratio [OR]: 0.20; 95% confidence interval [CI]: 0.001-0.396; p = 0.010). The rupture of the AVM was associated with poor neurologic outcome. The Lawton-Young Supplementary scale (LYSS) proved to be the most effective in predicting poor outcome. The existence of seizures, treatment-related complications, and conservative treatment was associated with the worsening of the mRS score, whereas the existence of hemorrhage was associated with the likelihood of disability. Our results suggest that poor neurologic status at diagnosis, AVM rupture, and conservative treatment were associated with worse outcome. Hemorrhage as initial presentation is related to disability, not with mRS worsening. The LYSS appeared to be the best method to predict outcome.

Case report of a 'snake thrombus' in the right heart: a rare finding on echocardiography.

Background A right heart thrombus originating from an inferior vena cava thrombosis (IVCT) is a rare entity. In accordance with venous thromboembolism (VTE), IVCT can be categorized as primary or secondary. Secondary ICVT can be the result of a predisposing hypercoagulable state and/or from external compression on the inferior vena cava (IVC) such as in case of malignancies. Renal cell carcinoma (RCC), amongst others, has been described in the context of secondary IVCT.Case summary An 80-year-old man was presented in our emergency department with complaints of dyspnoea and oedema. Echocardiography revealed a large snake-like thrombus in the IVC extending into the right atrium. Subsequent computed tomography resulted in a diagnosis of an RCC. The patient was considered to be in too poor clinical condition for surgical removal. In the next days, his condition deteriorated, after which palliative care was initiated and the patient deceased at day 12 of admission.Conclusion A right heart thrombus is a rare finding during echocardiography. This case demonstrates an incidental finding of a ‘snake thrombus’ in the IVC and right heart secondary to RCC. This case illustrates the importance and additional value of echocardiography in the setting of suspected right-sided heart failure.

Statin treatment reduces the risk of death among elderly frail patients: evidence from a large population-based cohort.

To assess the protective effect of statins in a large and unselected cohort of frail elderly subjects. The 460460 Lombardy residents (Italy), aged ≥65 years, who received ≥3 consecutive prescriptions of a statin during 2011-2012 were identified. A case-control study was performed, the cases being the cohort members who died during 2011-2018. Logistic regression was used to model the outcome risk associated with statin adherence. Adherence to drug therapy was measured by the proportion of the follow-up covered by prescriptions. The analysis was stratified according to four clinical categories (good, medium, poor, and very poor clinical status), based on different life expectancies, as assessed by a prognostic score which had been found to sensitively predict the risk of death. The 7-year death probability increased from 11% (good) to 52% (very poor clinical status). In each clinical status, there was a significant reduction of all-cause mortality as adherence to statin treatment increased. The reduction in the adjusted risk of mortality from the lowest to the highest adherence level was greatest among patients with a good clinical status (-56%) and progressively less among other cohort members, i.e. -48%, -44% and -47% in medium, poor, and very poor groups, respectively. Similar findings were obtained for the risk of cardiovascular mortality. In a real-life setting, adherence to statin treatment reduced the death risk also in frail elderly patients. However, in these patients, the benefit of statin treatment may be lower than in those in good clinical conditions.

Clinical Improvement and Effectiveness of Exercise-Based Pulmonary Rehabilitation in Patients With Idiopathic Pulmonary Fibrosis: A BRIEF ANALYTICAL REVIEW.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease associated with high mortality rates and poor clinical condition. Exercise-based pulmonary rehabilitation (EBPR) has been demonstrated to be effective in improving 6-min walk distance (6MWD), although the clinical improvement and effectiveness are less characterized. The current review examined the existing evidence of EBPR among patients with IPF and aimed to analyze the effect of EBPR on clinical improvement and effectiveness. A systematic databases search (MEDLINE/PubMed, EMBASE, and the Cochrane Library) was conducted for available publications as of January 2020. Randomized controlled trials (RCTs) and meta-analyses of RCTs examining the effect of EBPR in patients with IPF were reviewed. Mean difference for RCTs and weighted mean difference for meta-analyses between the EBPR arm and the usual-care arm in 6MWD were compared with the established minimal clinically important difference (MCID) of 30 m. Clinical improvement following EBPR was determined when mean difference and weighted mean difference were equal or exceeding the MCID. Effectiveness of EBPR was assessed using the number needed to treat (NNT) analysis. Five independent RCTs (including 21-61 patients/study) and five meta-analyses (including two to five studies with 62-169 patients/meta-analysis) were included. The mean difference of 6MWD ranged from 16-81 m in RCTs. Three of five RCTs demonstrated an average improvement that meets or exceeds the MCID. Two RCTs showed favorable improvement in 6MWD but did not reach the MCID. The weighted mean difference of 6MWD ranged from 27-49 m in the meta-analyses. Four of five meta-analyses showed an average improvement that meets or exceeds the MCID. One early meta-analysis of only two RCTs showed significant improvement, although did not reach the MCID. The NNT in three RCTs and four meta-analyses that met clinical improvement in 6MWD was one. This review provides novel evidence with respect to clinical improvement and high effectiveness of EBPR among patients with IPF. The results suggest that, on average, the majority of patients would be expected to clinically improve by completing the EBPR program. The findings further support the prescription of EBPR as clinically effective therapy and implementation as standard of care for patients with IPF. Future studies examining clinical improvement and effectiveness utilizing additional outcomes with the MCID are warranted.

Pulmonary arterial hypertension in families with hereditary hemorrhagic telangiectasia: a 13-year follow-up study

Abstract Background Pulmonary arterial hypertension (PAH) can occur in families with hereditary hemorrhagic telangiectasia (HHT), but it has not been well-characterized. Purpose This study sought to characterize the genetic defects, clinical and hemodynamic features, and outcomes of PAH patients in HHT families. Methods All HHT families with at least one case of PAH investigated in our center from January 2006 to December 2018 were enrolled in the study. We did whole-exome sequencing (WES) or whole-genome sequencing (WGS) to every proband and available family members. The clinical data, hemodynamic features and outcomes of PAH patients were reviewed. Results A total of 64 PAH patients in 57 families were enrolled. Only 7 (12.3%) families had more than one case of PAH. Activin-receptor-like kinase 1 (ALK-1) mutation and Endoglin (ENG) mutation were confirmed in 49 (86.0%) and 3 (5.3%) families and other 5 (8.8%) had no known mutation associated with HHT or PAH. The median age when PAH diagnosis was 22 [9–33] years and female was dominant (70.3%). Most patients (84.4%) had signs of HHT and anemia was recorded in 14 (21.9%) patients. Remarkably, these patients showed severely compromised hemodynamics with elevated mean pulmonary artery pressure (62 [51, 77] mm Hg) and pulmonary vascular resistance index (17.0 [11.2, 22.8] Wood units*m2). Also, impaired exercise capacity was recorded at diagnosis with decreased six-minute walking distance (410 [342–485] meters) and over half (54.7%) were in WHO functional class III or IV. The 1-, 3-, 5- and 10-year transplantation-free survival for the overall PAH patients was 95.0%, 75.9%, 67.1% and 36.4%, respectively. Anemia (HR: 4.24 [1.32–13.65], p=0.016) and CI &amp;lt;2.5 l/min/m2 (HR: 4.39 [1.20–16.09], p=0.026) were independent risk factors for mortality. Conclusions PAH in HHT families is a devastating condition characterized by a young age at PAH diagnosis, poor clinical status and outcomes mainly underlying ALK-1 mutation, which emphasizes the importance to pay attention to this group of patients. Transplantation-free survival Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Beijing Natural Science Foundation (7181009), the National Key Research and Development Program of China (2016YFC0901502)

Do a surrogate decision-maker's motives matter?

Do a surrogate decision-maker's motives matter?

Italian Association of Clinical Endocrinologists (AME) and Italian AACE Chapter Position Statement for Clinical Practice: Acromegaly - Part 2: Therapeutic Issues.

Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas. The therapeutic management of acromegaly always requires a personalized strategy. Normal age-matched IGF-I values are the treatment goal. Transsphenoidal surgery by an expert neurosurgeon is the primary treatment modality for most patients, especially if there are neurological complications. In patients with poor clinical conditions or who refuse surgery, primary medical treatment should be offered, firstly with somatostatin analogs (SSAs). In patients who do not reach hormonal targets with first-generation depot SSAs, a second pharmacological option with pasireotide LAR or pegvisomant (alone or combined with SSA) should be offered. Irradiation could be proposed to patients with surgical remnants who would like to be free from long-term medical therapies or those with persistent disease activity or tumor growth despite surgery or medical therapy. Since the therapeutic tools available enable therapeutic targets to be achieved in most cases, the challenge is to focus more on the quality of life.

Intracranial Meningiomas in the Elderly: Clinical, Surgical and Economic Evaluation. A Multicentric Experience.

Simple SummaryMeningiomas are the most common intracranial tumors. Given the increase in life expectancy and the widespread access and use of brain imaging, the incidence in the elderly population (≥65 years) is continuously increasing. The risk/benefit ratio of surgery in elderly patients with intracranial meningioma has not been clearly defined because of the lack of objective measurement tools. The aim of our work to understand the risk factors associated with postsurgical outcomes and how these risk factors affected postsurgical outcomes in elderly patients with intracranial meningioma.Meningioma is one of the most common intracranial tumors. It is benign and slow growing in the majority of cases. Given the increase in life expectancy and the number of radiological tests performed, the incidence in the elderly population (≥65 years) is continuously increasing. The surgical outcomes and prognostic factors in this age group are unclear. A retrospective analysis of all the patients treated for intracranial meningiomas in two different Italian institutions was performed. The clinical, radiological, surgical and follow-up data were retrospectively reviewed. Statistical analyses were performed to identify relationships between factors and outcomes. We also carried out an economic analysis. We analyzed 321 patients with intracranial meningioma. The mean age was 72.6 years (range, 65–90), with a female predominance (F/M, 1.41). Pre-operative deficits, cognitive impairment and seizures (p < 0.001) were associated with a worse post-operative Karnofsky performance scale (KPS) score (<80). A high pre-operative KPS score was associated with a good clinical and neurological outcome (p < 0.001). Being aged between 65 and 74 years, low surgical timing and Simpson removal grades of I and II were associated with a good outcome (p < 0.001). The length of hospitalization was significantly related to the outcome (p < 0.001). The complication rate was 14.3%. At 6-month follow-up, the mortality rate was 2.5%. The average cost was higher in patients with a pre-operative KPS score lower than 80. The outcome of intracranial-meningioma resection in elderly individuals is favorable when the pre-operative KPS score is >80. Treatment should be patient-specific, and additional factors should be considered. Patients with poor pre-operative clinical conditions might benefit from a combined strategy with partial resection and radiosurgery in order to reduce surgical timing and the complication rate.

Transcatheter Tricuspid Valve-in-Valve Replacement by Transatrial Approach

Reoperation on the tricuspid valve after prior heart valve surgery is associated with an increased operative risk due to a poor clinical status with severe heart failure and late presentation. Transcatheter tricuspid valve-in-valve implantation emerged as an attractive alternative to a high-risk redo surgery. The authors report a case of successful treatment of a failed bioprosthetic tricuspid valve in a 58-year-old woman with severe heart failure, decompensated cardiac cirrhosis and atrial fibrillation using transcatheter tricuspid valve-in-valve implantation of a Sapien 3 valve (Edwards Lifesciences, Irvine, California) via a transatrial approach. This case demonstrates the efficiency of this novel approach for the treatment of dysfunctional surgical tricuspid bioprosthetic valves and the technical feasibility and safety of a rarely used route.

Clinical Relevance of Changes in Peripheral Blood Cells After Intracranial Aneurysm Rupture

BackgroundThe rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. We sought to characterize the systemic response to IA rupture. MethodsWe included 19 patients in the acute phase of IA rupture and 20 control subjects. Flow cytometry was used to analyze alterations in the level of mononuclear leukocytes. Cell-related parameters, including the neutrophil-to-lymphocyte ratio (NL-R), lymphocyte-to-monocyte ratio (LM-R), platelet-to-lymphocyte ratio (PL-R), and systemic immune-inflammation index (SII), were calculated, and the relationship between the analyzed hematological parameters and clinical status was investigated. ResultsPatients with ruptured IAs presented with significantly higher white blood cells (WBC) and neutrophil counts but lower lymphocyte counts than control subjects. NL-R and SII values were higher and the LM-R was lower in the acute phase after IA rupture. Analyzing the severity of clinical status and the outcome of patients with subarachnoid hemorrhage, we found that patients with poor clinical status, as measured by the Glasgow Coma Scale (GCS) and the Hunt and Hess scale, had significantly lower lymphocyte counts and higher NL-R, PL-R and SII values than those with good clinical status. Additionally, patients with lower GCS scores presented a lower proportion of CD3+CD4-CD8- cells. Worse outcomes assessed at discharge were associated with lower lymphocyte counts but higher PL-R values. ConclusionsThe current study pointed to the significance of systemic immune and inflammatory responses after IA rupture and the potential clinical utility of hematological parameters, which can be easily calculated. In particular, the role of DN T cells and the significance of the SII as a marker related to clinical status should be further investigated.