Febrile rhabdomyolysis of unknown origin in refugees coming from West Africa through the Mediterranean

Abstract Objectives Cases of undiagnosed severe febrile rhabdomyolysis in refugees coming from West Africa, mainly from Nigeria, has been observed since May 2014. The aim of this study was to describe this phenomenon. Methods This was a multicentre retrospective observational study of cases of febrile rhabdomyolysis reported from May 2014 to December 2016 in 12 Italian centres. Results A total of 48 cases were observed, mainly in young males. The mean time interval between the day of departure from Libya and symptom onset was 26.2 days. An average 8.3 further days elapsed before medical care was sought. All patients were hospitalized with fever and very intense muscle aches. Creatine phosphokinase, aspartate aminotransferase, and lactate dehydrogenase values were abnormal in all cases. The rhabdomyolysis was ascribed to an infective agent in 16 (33.3%) cases. In the remaining cases, the aetiology was undefined. Four out of seven patients tested had sickle cell trait. No alcohol abuse or drug intake was reported, apart from a single reported case of khat ingestion. Conclusions The long incubation period does not support a mechanical cause of rhabdomyolysis. Furthermore, viral infections such as those caused by coxsackievirus are rarely associated with such a severe clinical presentation. It is hypothesized that other predisposing conditions like genetic factors, unknown infections, or unreported non-conventional remedies may be involved. Targeted surveillance of rhabdomyolysis cases is warranted

Dark sputum: An atypical presentation of primary pulmonary malignant melanoma

Primary melanoma of the lung is an extremely rare clinical entity. We found only 32 cases reported in literature, and in two of these multiple brain metastases were present. We describe a case of primary lung melanoma with brain and skin metastases that presented with an initial clinical diagnosis of pneumonia. A 55-year-old white man presented with cough productive of dark sputum and fever. A chest x-ray showed a right lung infiltration. After failure to respond to usual treatment for pneumonia, bronchoscopy examination and CT scan revealed a right pulmonary mass. The CT-guided biopsy confirmed a diagnosis of malignant melanoma. The primary lung origin of the tumor was demonstrated by the characteristic junctional pattern of melanoma cells. Further evaluation revealed metastases in the brain and in skin. Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease

The Adaptor Protein p66Shc Inhibits mTOR-Dependent Anabolic Metabolism

Adaptor proteins link surface receptors to intracellular signaling pathways and potentially control the way cells respond to nutrient availability. Mice deficient in p66Shc, the most recently evolved isoform of the Shc1 adaptor proteins and a mediator of receptor tyrosine kinase signaling, display resistance to diabetes and obesity. Using quantitative mass spectrometry, we found that p66Shc inhibited glucose metabolism. Depletion of p66Shc enhanced glycolysis and increased the allocation of glucose-derived carbon into anabolic metabolism, characteristics of a metabolic shift called the Warburg effect. This change in metabolism was mediated by the mammalian target of rapamycin (mTOR) because inhibition of mTOR with rapamycin reversed the glycolytic phenotype caused by p66Shc deficiency. Thus, unlike the other isoforms of Shc1, p66Shc appears to antagonize insulin and mTOR signaling, which limits glucose uptake and metabolism. Our results identify a critical inhibitory role for p66Shc in anabolic metabolism.National Institutes of Health (U.S.)United States. Dept. of DefenseW. M. Keck FoundationLAM FoundationNational Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award)National Institutes of Health (U.S.) (K99 Award

Impact of prosthesis-patient mismatch on cardiac events and midterm mortality after aortic valve replacement in patients with pure aortic stenosis

Background — Prosthesis-patient mismatch (PPM) occurs when the effective orifice area (EOA) of the prosthesis being implanted is too small in relation to body size, thus causing abnormally high transvalvular pressure gradients. The objective of this study was to examine the midterm impact of PPM on overall mortality and cardiac events after aortic valve replacement in patients with pure aortic stenosis. Methods and Results — The indexed EOA (EOAi) was estimated for each type and size of prosthesis being implanted in 315 consecutive patients with pure aortic stenosis. PPM was defined as an EOAi 0.80 cm2/m2 and was correlated with overall mortality and cardiac events. PPM was present in 47% of patients. The 5-year overall survival and cardiac event-free survival were 82 3% and 75 4%, respectively, in patients with PPM compared with 93 3% and 87 4% in patients with no PPM (P 0.01). In multivariate analysis, PPM was associated with a 4.2-fold (95% CI, 1.6 to 11.3) increase in the risk of overall mortality and 3.2-fold (95% CI, 1.5 to 6.8) increase in the risk of cardiac events. The other independent risk factors were history of heart failure, NHYA class III-IV, severe left ventricular hypertrophy, and absence of normal sinus rhythm before operation. Conclusions — PPM is an independent predictor of cardiac events and midterm mortality in patients with pure aortic stenosis undergoing aortic valve replacement. As opposed to other risk factors, PPM may be avoided or its severity may be reduced with the use of a preventive strategy at the time of operation

Leukocytes and creatinine may predict severity and guide management of ischemic colitis

BACKGROUND: Ischemic colitis (IC) is caused by a transient hypo-perfusion of the colon leading to mucosal ulcerations, inflammation, and hemorrhage. The primary aim was to identify predictive factors of endoscopic severity of IC. Secondary endpoints were to show epidemiology, clinical presentation, endoscopic findings, and outcomes of IC. METHODS: In this single-center retrospective analysis, IC was scored according to endoscopy as: grade 1 (hyperemia, 1 cm superficial, partially confluent ulcers); and grade 3 (deep or diffuse ulcers or necrosis). Then, IC was grouped into low- (grade 1) and high-grade (grades 2 and 3). Significant (P≤0.1) independent factor of severe IC at univariate analysis were entered into multivariate analysis and considered significant at P<0.05. RESULTS: 227 patients (male:female 60:167; mean age 72.7±16.2 years) were included. IC was scored as grade 1 in 137/227 (60.4%), grade 2 in 62/227 (27.3%), and grade 3 in 28/227 (12.3%) patients. At univariate analysis, age (74.9 vs. 71.3 years; P=0.09), diabetes (14.4% vs. 12.4%; P=0.09), and leukocytosis or creatinine elevation (74.4% vs. 60.6%; P=0.032) were associated with endoscopic high-grade IC. At multivariate analysis, leukocytosis and creatinine levels remained associated with high-grade IC (44.7% vs. 29.9%; odds ratio 1.92, 95% confidence interval 1.07-3.52; P=0.030). CONCLUSIONS: Although confounding factors cannot be excluded due to study design and patients' characteristics, leukocytosis and/or creatinine elevation at hospital admission were significantly related with endoscopic high-grade IC and might be used to stratify patients for the need of endoscopy

Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1

The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase–dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid–sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.National Institutes of Health (U.S.) (Grant R01 CA103866)National Institutes of Health (U.S.) (Grant AI47389)United States. Dept. of Defense (W81XWH-07-0448)National Institutes of Health (U.S.) (Fellowship F30CA180754)National Institutes of Health (U.S.) (Fellowship T32 GM007753)National Institutes of Health (U.S.) (Fellowship F31 AG044064)National Institutes of Health (U.S.) (Fellowship F31CA180271)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship ProgramAmerican Cancer Society (Ellison Medical Foundation. Postdoctoral Fellowship PF-13-356-01-TBE)Howard Hughes Medical Institut

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys