Antimicrobial Stewardship Teams in Veterans Affairs and Nonfederal Hospitals in the United States: A National Survey of Antimicrobial Stewardship Practices.

In a cross-sectional survey of US acute care hospitals, antimicrobial stewardship programs were present in most Veterans Affairs and nonfederal hospitals but varied in team composition, scope, and impact. Diagnostic stewardship was common across hospitals. Veterans Affairs hospitals had increased reach in outpatient settings. Telestewardship remains an opportunity in all hospital systems.

Proteomic analysis of nuclei dissected from fixed rat brain tissue using expression microdissection.

Expression microdissection (xMD) is a high-throughput, operator-independent technology that enables the procurement of specific cell populations from tissue specimens. In this method, histological sections are first stained for cellular markers via either chemical or immuno-guided methods, placed in close contact with an ethylene vinyl acetate (EVA) film, and exposed to a light source. The focal, transient heating of the stained cells or subcellular structures melts the EVA film selectively to the targets for procurement. In this report, we introduce a custom-designed flashcube system that permits consistent and reproducible microdissection of nuclei across an FFPE rat brain tissue section in milliseconds. In addition, we present a method to efficiently recover and combine captured proteins from multiple xMD films. Both light and scanning electron microscopy demonstrated captured nuclear structures. Shotgun proteomic analysis of the samples showed a significant enrichment in nuclear localized proteins, with an average 25% of recovered proteins localized to the nucleus, versus 15% for whole tissue controls (p < 0.001). Targeted mass spectrometry using multiple reaction monitoring (MRM) showed more impressive data, with a 3-fold enrichment in histones, and a concurrent depletion of proteins localized to the cytoplasm, cytoskeleton, and mitochondria. These data demonstrate that the flashcube-xMD technology is applicable to the proteomic study of a broad range of targets in molecular pathology.

Comorbid status in patients with osteomyelitis is associated with long-term incidence of extremity amputation.

INTRODUCTION: Osteomyelitis is associated with significant morbidity, including amputation. There are limited data on long-term amputation rates following an osteomyelitis diagnosis. We sought to determine the incidence of amputation in patients with osteomyelitis over 2 years. RESEARCH DESIGN AND METHODS: Observational cohort study of 1186 inpatients with osteomyelitis between 2004 and 2015 and stratified by osteomyelitis location status to evaluate the impact on amputation, mortality rates, readmission data, and inpatient days. RESULTS: Persons with diabetes had 3.65 times greater probability of lower extremity amputation (p<0.001), readmission (p<0.001), and longer inpatient stay (p<0.001) and had higher 2-year mortality (relative risk (RR) 1.23, p=0.0027), adjusting for risk factors. Male gender (RR 1.57, p<0.001), black race (RR 1.41, p<0.05), former smoking status (RR 1.38, p<0.01), myocardial infarction (RR 1.72, p<0.001), congestive heart failure (RR 1.56, p<0.001), peripheral vascular disease (RR 2.25, p<0.001) and renal disease (RR 1.756, p<0.001) were independently associated with amputation. Male gender (RR 1.39, p<0.01), black race (RR 1.27, p<0.05), diabetes (RR 2.77, p<0.001) and peripheral vascular disease (RR 1.59, p<0.001) had increased risk of lower, not upper, extremity amputation. CONCLUSIONS: Patients with osteomyelitis have higher rates of amputation and hospitalization. Clinicians must incorporate demographic and comorbid risk factors to protect against amputation.

Diagnosis and Antifungal Prophylaxis for COVID-19 Associated Pulmonary Aspergillosis.

The COVID-19 pandemic has redemonstrated the importance of the fungal-after-viral phenomenon, and the question of whether prophylaxis should be used to prevent COVID-19-associated pulmonary aspergillosis (CAPA). A distinct pathophysiology from invasive pulmonary aspergillosis (IPA), CAPA has an incidence that ranges from 5% to 30%, with significant mortality. The aim of this work was to describe the current diagnostic landscape of CAPA and review the existing literature on antifungal prophylaxis. A variety of definitions for CAPA have been described in the literature and the performance of the diagnostic tests for CAPA is limited, making diagnosis a challenge. There are only six studies that have investigated antifungal prophylaxis for CAPA. The two studied drugs have been posaconazole, either a liquid formulation via an oral gastric tube or an intravenous formulation, and inhaled amphotericin. While some studies have revealed promising results, they are limited by small sample sizes and bias inherent to retrospective studies. Additionally, as the COVID-19 pandemic changes and we see fewer intubated and critically ill patients, it will be more important to recognize these fungal-after-viral complications among non-critically ill, immunocompromised patients. Randomized controlled trials are needed to better understand the role of antifungal prophylaxis.

Transhiatal robot-assisted minimally invasive esophagectomy: unclear benefits compared to traditional transhiatal esophagectomy.

Esophagectomy is a high-risk operation, regardless of technique. Minimally invasive transthoracic esophagectomy could reduce length of stay and pulmonary complications compared to traditional open approaches, but the benefits of minimally invasive transhiatal esophagectomy are unclear. We performed a retrospective review of prospectively gathered data for open transhiatal esophagectomies (THEs) and transhiatal robot-assisted minimally invasive esophagectomies (TH-RAMIEs) performed at a high-volume academic center between 2013 and 2017. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for outcomes. 465 patients met inclusion criteria (378 THE and 87 TH-RAMIE). THE patients more likely had an ASA score of 3 + (89.1% vs 77.0%, p = 0.012), whereas TH-RAMIE patients more likely had a pathologic staging of 3+ (43.7% vs. 31.2%, p = 0.026). TH-RAMIE patients were less likely to receive epidurals (aOR 0.06, 95% confidence interval [CI] 0.03-0.14, p < 0.001), but epidural use itself was not associated with differences in outcomes. TH-RAMIE patients experienced higher rates of pulmonary complications (adjusted odds ratio [OR] 1.82, 95% CI 1.03-3.22, p = 0.040), particularly pulmonary embolus (aOR 5.20, 95% CI 1.30-20.82, p = 0.020). There were no statistically significant differences in lymph node harvest, unexpected ICU admission, length of stay, in-hospital mortality, or 30-day readmission or mortality rates. The TH-RAMIE approach had higher rates of pulmonary complications. There were no statistically significant advantages to the TH-RAMIE approach. Further investigation is needed to understand the benefits of a minimally invasive approach to the open transhiatal esophagectomy.

An 80-Year-Old Man With Persistent Enterococcus faecalis Bacteremia.

CASE PRESENTATION: An 80-year old man presented to the ED after being found down in his home. He had gone to the restroom to perform straight catheterization, as he normally does for his enlarged prostate, and was found slumped over and confused. On arrival to the ED, he was found to be in atrial fibrillation with rapid ventricular response, febrile, and hypotensive. CT imaging of his head, chest, and abdomen-pelvis was obtained. He was started on broad-spectrum antibiotics and norepinephrine infusion for presumed urinary septic shock and admitted to the medical critical care unit for further management.

Disentangling Race, Poverty, and Place in Disparities in Physical Activity.

Significant racial disparities in physical activity-a key protective health factor against obesity and cardiovascular disease-exist in the United States. Using data from the 1999-2004 National Health and Nutrition Examination Survey and the 2000 United States (US) Census, we estimated the impact of race, individual-level poverty, neighborhood-level poverty, and neighborhood racial composition on the odds of being physically active for 19,678 adults. Compared to whites, blacks had lower odds of being physically active. Individual poverty and neighborhood poverty were associated with decreased odds of being physically active among both whites and blacks. These findings underscore the importance of social context in understanding racial disparities in physical activity and suggest the need for future research to determine specific elements of the social context that drive disparities.

Ethnicity and Psychiatric Disorders.

Psychiatric disorders are one of the leading causes of disease-related disability in the world today. However, little is known about the ethnic variation of these disorders within populations. This is especially true in contexts outside of the United States and the European Diaspora. This study provides new evidence from South Asia on ethnic differences in Major Depressive Episode, Major Depressive Disorder, Panic Attack, Panic Disorder, Post-Traumatic Stress Disorder, and Intermittent Explosive Disorder. We use data from 400 adult interviews conducted in Nepal in a controlled comparison design as a case study. We use a series of multilevel logistic regression models to predict ethnic group differences in psychiatric disorders and episodes with measures from clinically validated World Mental Health survey instruments. Compared to the Brahmin/Chhetri group, we found historically excluded Dalits had statistically significantly higher odds of almost all psychiatric disorders and episodes. We also found that historically resilient Janajatis had statistically significantly lower odds of being diagnosed with PTSD than the majority Brahmin/Chhetri group. We also found no significant gender difference in MDD or MDE. Psychiatric disorders and episodes vary significantly by ethnicity within a rural Asian population, but gender differences are small.

Genetic mapping of a susceptibility locus for disc herniation and spastic paraplegia on 6q23.3-q24.1.

It has been suggested that a genetic factor(s) or a familial predisposition may contribute to the clinical manifestations of disc herniation; moreover, no genetic linkage between spinal disc herniation and spastic paraplegia has ever been described. A family with consanguineous parents and four of eight sibs affected by multiple disc herniations and spastic paraplegia was clinically and genetically analysed. Surgery caused partial improvement in all of them. After the exclusion of type II collagen and vitamin D receptor genes and the recessive loci for HSPs, a genome wide search was performed with about 500 fluorescent markers. Positive lod score values were obtained for chromosome 6q22.31-q24.1, with evidence of three homozygous intervals. The maximum multipoint lod score of 3.28 was obtained in only one interval, between markers D6S1699 and D6S314. On the whole, a susceptibility locus for disc herniation and autosomal recessive spastic paraplegia was found on chromosome 6q23.3-q24.1. This is the first time that disc herniation and the associated neurological syndrome has been linked to a human chromosomal region.

Sensory, motor, and autonomic neuropathy in patients with multiple symmetric lipomatosis.

Clinical evaluation of 33 male patients affected by multiple symmetric lipomatosis has revealed a previously unreported high prevalence of somatic and autonomic neuropathies. In 84% of the patients, clinical examination revealed signs or symptoms of neural disturbances, ranging from a vibratory sensory loss to severely incapacitating trophic ulcers or Charcot's arthropathy. Electrodiagnostic investigations demonstrated a significant reduction of motor and sensory conduction velocity in the peroneal and sural nerves. Morphometric studies of nerve and muscle biopsies from five patients with multiple symmetric lipomatosis revealed a significant reduction in myelinated fiber density (4435 +/- 593 fibers/mm2 in MSL vs 7660 +/- 800 in controls; p less than 0.05), a selective reduction in the large fibers of 7 to 10 micron in diameter, and signs of chronic denervation-reinnervation processes. Bedside tests for autonomic neuropathy were abnormal in 15 of 20 patients studied. Metabolic studies in these patients confirmed a significant increase in plasma high-density lipoprotein fractions consistent with the diagnosis of hyperalphalipoproteinemia, and a significant reduction in plasma low-density lipoprotein fractions (hypobetalipoproteinemia) associated with a marked enhancement of lipoprotein lipase activity in adipose tissue. Thus, a metabolic factor has to be considered in the pathogenesis of MSL neuropathy.

Carnitine palmityl transferase deficiency: clinical variability, carrier detection, and autosomal-recessive inheritance.

A 21-year-old man had recurrent myoglobinuria; his 28-year-old sister had symptoms of fatigability. During prolonged fasting, serum free fatty acid rose in both siblings, but only the sister produced ketone bodies and had elevated creatine phosphokinase activity. Carnitine palmityl transferase (CPT) activity was less than 30% of normal in muscle and platelets. Liver biopsy disclosed a low level of the enzyme in the brother. The parents had intermediate levels of the enzyme in platelets. CPT deficiency seems to have an autosomal-recessive pattern of inheritance and a variable phenotypic expression.

Intense focal expression of vascular endothelial growth-factor messenger-RNA in human intracranial neoplasms - association with regions of necrosis.

To examine the potential involvement of vascular endothelial growth factor (VEGF) in vascular changes which occur in human intracranial neoplasms, we examined a series of tumor specimens for expression of VEGF mRNA by in situ hybridization. VEGF was expressed at high levels by tumor cells in discrete regions in several of the tumors examined. The highest levels were detected in glioblastomas. The presence and location of foci of intense VEGF mRNA expression were, paradoxically well correlated with the presence of necrobiosis within the tumor mass. A less consistent association was observed between VEGF expression and either the degree of vascularization or endothelial cell proliferation. Since VEGF has been shown to induce tissue factor expression, VEGF itself may be involved in the pathogenesis of necrosis. Our findings provide evidence that VEGF mRNA is highly expressed in specific intracranial malignancies and suggest that VEGF plays a complex and multifunctional role in vascular biology.

Carnitine and acyltransferase in experimental neurogenic atrophies: changes with treatment.

Carnitine level and carnitine palmityl transferase (CPT) activity were investigated in muscles of patients with infantile and juvenile spinal muscular atrophy and polyneuropathies. A significant decrease of both carnitine and CPT was found in the infantile spinal muscular atrophy, but not in the other neurogenic muscle atrophies. These findings were compared with the experimental effect of denervation and reinnervation upon the lipid metabolism in soleus and extensor digitorum longus (EDL) of adult and newborn rats. Twenty-one days after denervation free and total carnitine decreased significantly in both EDL (P less than 0.001) and soleus (P less than 0.05) of adult animals. CPT activity was significantly decreased in the soleus 50 days after denervation (P less than 0.005). Long-term reinnervation restored the level of carnitine fraction and CPT activity. L-carnitine treatment for 21 days restored the level of free carnitine to normal in the soleus of denervated adult animals. Denervation in newborn rats influenced carnitine concentration in soleus and EDL to a lesser extent; the treatment with L-carnitine raised short-chain acylcarnitines in denervated muscles, while reinnervation restored carnitine level within 50 days.

Peroneal muscular atrophy with ataxia and partial myoclonic epilepsy.

Two brothers, 17 and 11 years old, presented with pes cavus, absence of deep tendon reflexes, péripheral vibratory sensory loss, ataxia, tremor, nystagmus, dysarthria and partial myoclonic epilepsy. Electromyography showed severe slowing of motor conduction velocity in the lower extremities and increased distal latencies. A peroneal nerve biopsy showed absence of myelin sheath in most fibres resulting in numerous demyelinated nerve fibres. The father and seven uncles on the paternal side had pes cavus, hammer toes and moderate vibratory peripheral sensory loss. Three of seven siblings had slow motor conduction velocities on EMG. None had EEG abnormalities. Epilepsy started at an early age in both patients with myoclonic jerks of the right arm especially during sleep. EEG recordings were characterized by focal or diffuse epileptiform discharges. In the elder brother a partial motor epileptic status occurred with adversive seizures involving the right side of the body. He died of a broncopneumonia after 3 days of this epileptic status. Histopathological examination showed a severe demyelination of dentato-rubral pathways in the cerebellum and a partial degeneration of Goll and Burdach's tracts in the cervical spinal cord. The nosological classification of this syndrome is discussed and an autosomal dominant inheritance with incomplete penetrance or variable expressivity is suggested.

Ataxia and congenital muscular dystrophy: the follow-up of a new specific phenotype.

Cerebellar hypoplasia may, at neuroimaging studies, be found in association with congenital muscular dystrophy (CMD), although it is an extremely rare occurrence. We here report on three CMD patients who underwent a longitudinal evaluation of clinical and neuroimaging features for a mean period of 18 years. Case 1, a 22-year-old woman, and cases 2 and 3, brothers aged 26 and 20 years, respectively, had presented a mild to moderate muscular weakness and increased serum creatine kinase (CK) levels since birth. All cases were diagnosed in the first years of life, with identification of evident dystrophic changes at muscle biopsy and moderate to severe cerebellar hypoplasia at brain computed tomography (CT) scan. Subsequently, all the patients underwent a second muscle biopsy, with immunostaining and immunoblot analysis, which showed normal values for merosin, dystrophin and dystrophin-related proteins. During the longitudinal study, the patients underwent repeated neurological and psychiatric examinations, serum CK controls, intellectual ability assessments and neuroimaging evaluations (CT and/or magnetic resonance imaging (MRI)). In all cases, these investigations indicated a mild to moderate deficit in the proximal muscles and a clear-cut cerebellar syndrome which, it was assumed, had been present since the first years. The patients also presented some intellectual difficulties, with an IQ of 0.69 in case 1, 0.83 in case 2 and 0.61 in case 3. The clinical course of all the patients was static, and all symptoms of the combined muscle and brain involvement persisted. Nor were any changes in the cerebellar hypoplasia observed at repeat MRIs. Findings obtained by us on the longitudinal study and a review of the literature indicate that cerebellar hypoplasia and merosin-positive CMD constitute a particular clinical phenotype, mainly characterized by an ataxic syndrome associated with a non-severe muscular involvement and a possible mild intellectual impairment.

The natural history of cardiac involvement in myotonic dystrophy: an eight-year follow-up in 17 patients.

We evaluated the progression of conduction system and myocardial disease in 17 asymptomatic myotonic dystrophy patients by clinical evaluation, electrocardiography, vector cardiography, and echocardiography. An exercise test was done in 10 patients. After 8 years, a follow-up study of 12 of the 17 original patients was done with a similar protocol. During this period, 2 patients died: one of sudden death while the other had acute left ventricular failure. In our first control study, we found EKG abnormalities in 15 of our patients, consisting mostly of conduction defects or pseudonecrotic patterns. In our second control, all patients had conduction system disease and, in addition, 3 of them had premature ventricular beats. One patient developed dilated cardiomyopathy. In 6 patients, structural involvement of the right ventricle was found. We conclude that even in asymptomatic myotonic dystrophy patients a conduction system deficit is present and progresses, and cardiac death may occur in about 12% of these patients.

[Muscular diseases: epidemiology of progressive muscular dystrophies]. / Malattie muscolari: l'epidemiologia delle distrofie muscolari progressive.

Epidemiology of muscular dystrophies has been important in the prevention of these diseases. In fact the genetic counselling, after a preliminary epidemiological investigation, reduced the incidence rate of Duchenne muscular dystrophy in the Veneto Region. Furthermore the new biochemical data on dismetabolic muscular diseases revealed a future strategy in the early identification of muscular dystrophies for their epidemiology and genetic prevention as well as for the new systems of research used in the field of muscular dystrophies.

[Catamnestic findings in syringomyelia in the province of Padua]. / Rilievi catamnestici sulla siringomielia in provincia di Padova.

While performing this research, 107 patients affected by syringomyelia were found, of which 35 were from the Padova province. The epidemiological study showed a progressive decrease of the disease in the last 40 years and a higher frequency in the rural area in comparison to the urban area. The data of prevalence in the region were also evaluated and compared with previous studies in other countries. The clinical studies, including a 20 years follow-up on a group of 25 patients, showed a slowly progressive impairment of the physical capacity without complete handicap, which had occurred in 2 of the group. The Authors suggest a constant clinical survey of these patients to encourage and support their social and professional activities.

[Benign muscular dystrophy with hypergonadotrophic hypogonadism and congenital cataract]. / Miodistrofia benigna con ipogonadismo ipergonadotropo e cataratta congenita

A syndrome characterized by benig muscular dystrophy, hypergonadotropic hypogonadism, congenital cataract and normal karyotype is reported. A similar condition was described by Bassöe. The patient's family tree revealed a number of isolated cases presenting some component of the syndrome, suggesting that this is connected with a recessive autosomic gene, probably with pleiotropic effect. The muscular disorder was absent in most of the other family members and its clinical signs were probably favoured by the low plasma level of testosterone with consequent reduced myotrophic action. The simultaneous presence of congenital cataract links the syndrome on the one hand to Steinert's myotonic dystrophy, although there were no clinical or electromyographic signs of myotonia, and on the other to other hereditary or familial neuroectodermal syndromes, compared to which it presents specific differential traits.

Haemoglobin E in pregnancy. A case report. Diagnosis, familiar study and counselling, follow up until delivery and new-born observation.

Haemoglobin E is a beta chain variant quite common in Southeastern Asia. The case of a gravid Thai woman with a microcytic anaemia is reported. The diagnosis of homozygous haemoglobin E was suspected on the basis of ethnic considerations when analysis of her haemoglobin showed the absence of normal HbA1 and about 100% of a variant Hb with electrophoretic mobility with HbC and HbA2. Identification of the haemoglobin variant was performed by using an association of alkaline electrophoresis on agarose gel, acid electrophoresis on agarose gel, haemoglobin isoelectrofocusing, high performance liquid chromatography. A study of haemoglobin pattern in the partner, parents and siblings was also performed. Pregnancy continued without any problems until the 40th week when a caesarean section was performed due to a difficult labour with foetal distress. The haemoglobin pattern of the new-born was studied at birth and after 1 year; as expected, it was quite normal at birth and a heterozygous condition for HbE was observed after 1 year. HbE, in even heterozygous and homozygous states, gives a mild clinical picture but its association with other haemoglobinopathies, such as a double heterozygous state (i.e. HbE/beta Thalassaemia) gives rise to a severe transfusion dependent thalassaemia syndrome. It is the authors' opinion that only a strict interaction between obstetricians and pathologists is the possible correct answer to the new diagnostic question proposed by a rapidly evolving inter-ethnic society.