Case report: Broad insertion of a large subscapularis tendon in association with congenital absence of the long head of the biceps tendon

Abstract

Congenital absence of the long head of the biceps (LHB) tendon is a rare variation in shoulder anatomy. The authors present a case of congenital absence of the long head of the biceps tendon associated with a large insertion of the subscapularis muscle. The patient initially presented with shoulder pain on overhead activity. Shoulder examination was negative for signs of a torn biceps tendon. MRI revealed congenital absence of the LHB tendon, a rim rent tear of the supraspinatus, and a large insertion of the subscapularis muscle. This is the first reported case describing a large insertion of the subscapularis muscle associated with absence of the LHB tendon.5

https://ift.tt/2sQDtel

Actinium-225 for Targeted α Therapy: Coordination Chemistry and Current Chelation Approaches

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2LJAxY2

Development and internal validation of a multivariable prediction model for tinnitus recovery following unilateral cochlear implantation: a cross-sectional retrospective study

Objective

To develop and internally validate a prediction model for tinnitus recovery following unilateral cochlear implantation.

Design

A cross-sectional retrospective study.

Setting

A questionnaire concerning tinnitus was sent to patients with bilateral severe to profound hearing loss, who underwent unilateral cochlear implantation at the University Medical Center Utrecht, the Netherlands, between 1 January 2006 and 31 December 2015.

Participants

Of 137 included patients, 87 patients experienced tinnitus preoperatively. Data of these 87 patients were used to develop the prediction model.

Primary and secondary outcome measures

The outcome of the prediction model was tinnitus recovery. Investigated predictors were: age, gender, duration of deafness, preoperative hearing performance, tinnitus duration, severity and localisation, follow-up duration, localisation of cochlear implant (CI) compared with tinnitus side, surgical approach, insertion depth of the electrode, CI brand and difference in hearing threshold following cochlear implantation. Multivariable backward logistic regression was performed. Missing data were handled using multiple imputation. The performance of the model was assessed by the calibrative and discriminative ability of the model. The prediction model was internally validated using bootstrapping techniques.

Results

The tinnitus recovery rate was 40%. A lower preoperative Consonant-Vowel-Consonant (CVC) score, unilateral localisation of tinnitus and larger deterioration of residual hearing at 250 Hz revealed to be relevant predictors for tinnitus recovery. The area under the receiver operating characteristics curve (AUC) of the initial model was 0.722 (IQR: 0.703–0.729). After internal validation of this prediction model, the AUC decreased to 0.696 (IQR: 0.667–0.700).

Conclusion and relevance

Lower preoperative CVC score, unilateral localisation of tinnitus and larger deterioration of residual hearing at 250 Hz were significant predictors for tinnitus recovery following unilateral cochlear implantation. The performance of the model developed in this retrospective study is promising. However, before clinical use of the model, the conduction of a larger prospective study is recommended.

https://ift.tt/2LJJi4e

Obstacles to diagnosis and treatment of Lyme disease in the USA: a qualitative study

Objective

For many individuals with Lyme disease, prompt treatment leads to rapid resolution of infection. However, severe complications can occur if treatment is delayed. Our objective was to identify themes around belated diagnosis or treatment of Lyme disease using the General Model of Total Patient Delay (GMTPD).

Design

We conducted a qualitative interview study using indepth telephone interviews.

Setting

Participants were patients from a large, integrated health system in the state of Pennsylvania, USA.

Participants

There were 26 participants. Participants had to have a diagnosis of Lyme disease between 2014 and 2017 and a positive IgG western blot. We used a stratified purposeful sampling design to identify patients with and without late Lyme disease manifestations. To ensure variation in care experiences, we oversampled patients diagnosed outside of primary care.

Outcome measures

We asked participants about their experience from first Lyme disease symptoms to treatment. We applied an iterative coding process to identify key themes and then synthesised codes into higher order codes representing the GMTPD stages: appraisal delay (symptom to recognition of illness); illness delay (inferring illness to deciding to seek help); behavioural delay (deciding to seek help to the act of seeking help); scheduling delay (seeking help to attending an appointment); and treatment delay (attending appointment to treatment).

Results

Appraisal delay themes included symptom misattribution, intermittent symptoms and misperceptions about the necessity of a bull's-eye rash. Health insurance status was a driver of illness and behavioural delays. Scheduling delay was not noted by participants, in part, because 10 of the 26 patients went to urgent care or emergency department settings. Misdiagnoses were more common in these settings, contributing to treatment delay.

Conclusion

Our study identified potentially modifiable risk factors for belated treatment. Targeting these risk factors may minimise time to treatment and reduce the occurrence of preventable complications.

https://ift.tt/2JJDLNP

The Veterans Metrics Initiative study of US veterans experiences during their transition from military service

Purpose

Efforts to promote the health and well-being of military veterans have been criticised for being inadequately informed of veterans' most pressing needs as they separate from military service, as well as the programmes that are most likely to meet these needs. The current article summarises limitations of the current literature and introduces The Veterans Metrics Initiative (TVMI) study, a longitudinal assessment of US veterans' well-being and programme use in the first three years after they separate from military service. Veterans were assessed within 3 months of military separation and will complete five additional assessments at 6-month intervals during the subsequent period.

Participants

The TVMI study cohort consists of a national sample of 9566 newly separated US veterans that were recruited in the fall of 2016.

Findings to date

The TVMI sample includes representation from all branches of service, men and women, and officers and enlisted personnel. Although representative of the larger population on many characteristics, differential response rates were observed for some subgroups, necessitating the development of non-response bias weights. Comparisons between unweighed and weighted results suggest that the weighting procedure adequately adjusts for observed differences.

Future plans

Analyses are under way to examine veterans' well-being and programme use in the period following separation after military service, as well as factors associated with poor outcomes. We have also begun to decompose programmes into their core components to facilitate examination of how these components relate to well-being. Once our third data collection is complete, we will examine factors related to different patterns of readjustment over time.

https://ift.tt/2HFP2JG

Effectiveness of the Gold Standard Programme (GSP) for smoking cessation on smokers with and without a severe mental disorder: a Danish cohort study

Objectives

We compared the effectiveness of an intensive smoking cessation intervention among smokers with and without a severe mental disorder (SMD) and identified factors associated with successful quitting. The main hypothesis was that smokers with an SMD would be less likely to stay continuously smoke-free for 6 months.

Design

A prospective cohort study.

Setting

In all, 302 smoking cessation clinics in Denmark from municipal clinics, pharmacies, hospitals, midwives, primary care facilities and other private providers who reported data to the national Danish Smoking Cessation Database from 2006 to 2016 participated in this study.

Participants

A total of 38 293 patients from the Danish Smoking Cessation Database. Patients with an SMD were identified by linking data to the Danish National Patient Register. Diagnoses of organic mental disorders (F0 chapter) or intellectual disabilities (F7 chapter) were not included. Smokers ≥18 years old who were attending a Gold Standard Programme (GSP) with planned follow-up were included. Smokers not wanting contact after 6 months were excluded.

Interventions

A comprehensive manual-based smoking cessation intervention comprising five meetings over a 6-week period (the GSP).

Main outcome measures

Self-reported continuous abstinence at the 6-month follow-up.

Results

In all, 69% of the participants participated in the follow-up after 6 months. The overall rate of successful quitting was high but significantly lower in SMD smokers (29% vs 38%; OR 0.74; 95% CI 0.68 to 0.80). Variables associated with successful quitting were compliance (defined as attending ≥75% of the planned meetings), older age and male gender as well as not being disadvantaged, heavy smoking or recommendation of intervention by health professionals.

Conclusions

Only 29% of smokers with an SMD successfully quit smoking which was significantly lower than the 38% of smokers without an SMD. Compliance was the most important predictor for successful quitting.

https://ift.tt/2JLhAXC

Observational study of associations between visual imagery and measures of depression, anxiety and post-traumatic stress among active-duty military service members with traumatic brain injury at the Walter Reed National Military Medical Center

Objectives

The study aimed tocompare recurring themes in the artistic expression of military service members (SMs) with post-traumatic stress disorder (PTSD), traumatic brain injury and psychological health (PH) conditions with measurable psychiatric diagnoses. Affective symptoms and struggles related to verbally expressing information can limit communication in individuals with symptoms of PTSD and deployment-related health conditions. Visual self-expression through art therapy is an alternative way for SMs with PTSD and other PH conditions to communicate their lived experiences. This study offers the first systematic examination of the associations between visual self-expression and standardised clinical self-report measures.

Design

Observational study of correlations between clinical symptoms of post-traumatic stress, depression and anxiety and visual themes in mask imagery.

Setting

The National Intrepid Center of Excellence at the Walter Reed National Military Medical Center, Bethesda, Maryland, USA.

Participants

Active-duty military SMs (n=370) with a history of traumatic brain injury, post-traumatic stress symptoms and related PH conditions.

Intervention

The masks used for analysis were created by the SMs during art therapy sessions in week 1 of a 4-week integrative treatment programme.

Primary outcomes

Associations between scores on the PTSD Checklist–Military, Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale on visual themes in depictions of aspects of individual identity (psychological injury, military symbols, military identity and visual metaphors).

Results

Visual and clinical data comparisons indicate that SMs who depicted psychological injury had higher scores for post-traumatic stress and depression. The depiction of military unit identity, nature metaphors, sociocultural metaphors, and cultural and historical characters was associated with lower post-traumatic stress, depression and anxiety scores. Colour-related symbolism and fragmented military symbols were associated with higher anxiety, depression and post-traumatic stress scores.

Conclusions

Emergent patterns of resilience and risk embedded in the use of images created by the participants could provide valuable information for patients, clinicians and caregivers.

https://ift.tt/2LHOHsp

Patient-reported outcome measurements in clinical routine of trauma, spine and craniomaxillofacial surgeons: between expectations and reality: a survey among 1212 surgeons

Objective

To gain information about the advantages/disadvantages of an implementation of patient-reported outcome measures (PROM) into the clinical routine of trauma/orthopaedic surgeons, and to identify the technical constraints confronting a successful implementation of PROMs.

Design

Online survey.

Participants

Surgeons who are members of the AO Foundation.

Measures

Participants answered questions regarding demographics, their familiarity with specific and generic PROMs and the use of PROMs in clinical routine. Furthermore, reasons for/against using PROMs, why not used more often, prerequisites to implement PROMs into clinical routine and whether PROMs would be implemented if adequate tools/technologies were available, were solicited. X² tests and multivariable logistic regressions were conducted to evaluate the effect of the AO Region, surgeon specialisation, current position, clinical experience, and workplace on the familiarity with disease-specific PROMs, the familiarity with generic PROMs and the current use of PROMs. Exploratory factor analysis was used to identify issues underlying the extent of PROM usage.

Results

1212 surgeons completed the survey (response rate: 6.8%; margin of error: ±2.72%): 54.2% were trauma/orthopaedic surgeons, 16.6% were spine surgeons, 27.9% were craniomaxillofacial surgeons and 16 had no defined specialty. Working in a certain AO Region, surgical specialisation and current workplace were associated with a higher familiarity of disease-specific PROMs and the use of PROMs in daily clinical routine (p≤0.05). Exploratory factor analysis identified four categories important for the use of PROMs and two categories preventing the use of PROMs. In case of the availability of an adequate tool, 66.2% of surgeons would implement PROMs in clinical routine.

Conclusions

Our survey results provide an understanding of the use of PROMs in clinical routine. There is consensus on the usefulness of PROMs. User-friendly and efficient tools/technologies would be a prerequisite for the daily use of PROMs. Additionally, educational efforts and/or policies might help.

https://ift.tt/2JFScm7

Recurrent meningitis caused by idiopathic cerebrospinal fluid rhinorrhoea from the sphenoid sinus

Description

A 41-year-old woman with 7 days of fever and headache had loss of consciousness 1 day prior to presentation. Despite the absence of trauma or other significant medical history, she had two episodes of meningitis in the previous 6 months. Physical examination showed no nuchal rigidity or abnormal findings on nasal endoscopy. Lumbar puncture showed a cerebrospinal fluid cell count of 750/μl. CT showed a bony defect of the posterior wall of the sphenoid sinus, which was filled with a soft tissue density. MRI showed fluid intensity in the same area (figure 1A, B). The diagnosis was recurrent meningitis due to possible idiopathic cerebrospinal fluid rhinorrhoea. Although a cisternogram is normally recommended, emergency drainage of the sphenoid sinus with antibiotic treatment was prioritised because of her deteriorating condition. With various possible diagnoses, an experienced surgeon operated on the patient. 

Figure 1

A bony defect of...

https://ift.tt/2y61F1k

Persistent elevation of carcinoembryonic antigen as first presentation of a medullary thyroid carcinoma

Carcinoembryonic antigen (CEA) is still the most widely used tumour marker for gastrointestinal cancer. CEA was originally thought to be a specific marker for colorectal cancer, but it turned out to be a non-specific marker for further studies. CEA levels can be elevated in breast, lung and liver cancers, among others, including medullary thyroid cancer. The authors report a case of a 73-year-old woman who had a right hemicolectomy for an ascending colon adenocarcinoma and showed a persistent elevation in the CEA marker during follow-up. After several imaging tests, recurrence of the colon cancer was not found, but the presence of thyroid nodules had been detected. The diagnosis of a medullary thyroid carcinoma was made after the finding of a high value of calcitonin. The patient had a total thyroidectomy with resection of the central and lateral lymph nodes.

https://ift.tt/2y4BUP4

Bronchogenic cyst infection presenting as pleuropericarditis

Description 

A 17-year-old woman was admitted to the emergency department with a 3-day history of dyspnoea (New York Heart Association Class II) and typical pleuritic pain following a 1-week history of cough and fever. Pneumonia was diagnosed based on a chest X-ray (figure 1A), and amoxicillin–clavulanate treatment was initiated. After 48 hours, the patient developed hypotension and tachycardia. Given hypotension, ongoing fever and rising C reactive protein despite antibiotic treatment, she was referred to the intensive care unit. On admission, an echocardiography was performed. A circumferential pericardial effusion with 14 mm maximum diameter adjacent to the right ventricle was detected, without haemodynamic compromise at the time. Besides, left pleural effusion was evidenced. An ultrasound-guided thoracentesis was conducted. Pleural fluid testing revealed the following findings: white blood cells (WBC) count 11.10⁹/Literwith 90% neutrophils, proteins 38 g/L, pH 7.36, glucose 6.3 mmol/L and lactate dehydrogenase (LDH) 492 IU/L. The culture exhibited no organism,...

https://ift.tt/2l2DbwA

Septic arthritis of the temporomandibular joint leading to an epidural abscess

Septic arthritis of the temporomandibular joint (TMJ) is rare, but patients with this diagnosis are at high risk for significant morbidity. We present a case of a 15-year-old man who presented with increasing trismus for 3 days. He had only minimal discomfort and swelling of the right cheek and temporal region, and pericoronitis of an impacted wisdom tooth was suspected. Under intravenous antibiotics, pain subsided, but trismus and a slight swelling remained. CT scan showed septic arthritis of the TMJ with an abscess formation penetrating into the epidural space. Immediate drainage and craniotomy were performed. Under intravenous antibiotics, the patient made a full recovery. The source of infection remained undetermined. To our knowledge, this is the first reported case of septic arthritis of the TMJ spreading into the epidural space.

https://ift.tt/2t1YmSS

Dentin dysplasia: diagnostic challenges

Dentin dysplasia(DD) is a rare autosomal dominant disorder associated with disturbance of the dentin. While the crowns appear clinically normal, on radiography, the pulp spaces appear partially or completely obliterated, with short blunted roots, and multiple periapical radiolucencies affecting the apparently sound teeth. Clinical signs include spontaneous abscess formation or increased tooth mobility which can lead to exfoliation. DD can therefore have a significant impact on the patient's dentition, and treatment is often challenging. Shields' classification of dentin disorders has been recently criticised for failing to consider differential variations and expressions of these disorders. This paper describes a case of a 23-year-old woman with previously undiagnosed DD, who presented with clinical and histological features belonging to several of these diseases, thus highlighting the potential diagnostic challenges faced with Shields' classification.

https://ift.tt/2l2D9Vu

Osteoporosis and malignancy: a dicey combination

Osteoporosis is the most common metabolic bone disorder worldwide, especially in women. Postmenopausal status is the most common risk factor for osteoporosis in elderly women. The operational diagnosis of osteoporosis is usually made with the help of central dual energy X-ray absorptiometry scan. Clinically, osteoporosis is suspected in the background of one or more fractures of the hip, vertebra, proximal humerus or pelvis in the absence of local disease or high-energy trauma. Serious underlying illness can present with vertebral fractures and can be missed if other clues from clinical examination and investigations are overlooked. We report a case emphasising this aspect.

https://ift.tt/2y61BP8

Horseshoe kidney with unilateral single ectopic ureter

The horseshoe kidney (HSK) is not an uncommon entity with an incidence of about 1 in 400 or 0.25% of the general population. It is also more commonly found in men as compared with women in a ratio of 2:1.An increased association of genitourinary anomalies have been found with HSK.Duplication of ureters occurs in 10% of HSKs. However, the association of HSK with single-system ectopic ureter is extremely rare. To our knowledge, no case with similar presentation has been reported in literature. Most cases of HSK with bilateral single ectopic ureters have been described. The aim of this report is to highlight the radiological and surgical findings in a case of HSK with unilateral single ectopic ureter.

https://ift.tt/2y61Ae2

Traumatic corneal perforation with exteriorisation of Ahmed glaucoma valve tube

We report a rare case of traumatic corneal perforation with Ahmed glaucoma valve (AGV) tube. A 5-year-old female child, diagnosed with refractory glaucoma, had undergone AGV implantation, presented with the posterior migration of AGV tube after trauma to the eye. The detailed ocular history, ophthalmic findings, clinical course and surgical management are discussed.

https://ift.tt/2l2D6cg

Metachronous renal Ewing sarcoma/primitive neuroectodermal tumour in a survivor of Burkitt lymphoma

We present a case of a 14-year-old girl who was diagnosed with Burkitt lymphoma in 2014. She was managed with chemotherapy and remained in remission for 3 years. On her surveillance imaging in 2017, a left-sided renal neoplastic mass was incidentally discovered. She underwent nephrectomy and pathology of the resected specimen revealed small cell tumour of the kidney with features favouring renal Ewing sarcoma/primitive neuroectodermal tumour. Molecular genetic analysis by fluorescence in situ hybridisation was performed which showed translocation of 22q12, thereby confirming the diagnosis. This is a rare secondary malignancy and an unusual association. This case highlights the importance and diagnostic dilemmas of rare secondary tumours in patients with such haematological malignancies and discusses its possible pathogenetic aspects.

https://ift.tt/2y61yCW

Diagnosis of Richter transformation in chronic lymphocytic leukemia: histology tips the scales

Abstract

Development of diffuse large B-cell lymphoma in chronic lymphocytic leukemia, so-called Richter transformation (RT), occurs in 2–5% of patients and is associated with poor outcome. The clinical features of RT are fairly non-specific and unable to discriminate transformation from other mimics. In case of clinically suspected RT, a CT/MRT is recommended, and FDG-PET/CT may help to select the site of biopsy. Radiological features suggestive of RT have been defined, but there are only limited data about their predictive value, and histological confirmation is still considered the gold standard for RT diagnosis. We retrospectively analyzed 34 patients with clinically suspected RT and available radiological and histological data. A histopathological diagnosis of RT with concordant clinical and radiological findings was obtained in 13 patients. In 18 patients, CT did not show features of transformation, concordant with lack of RT in the biopsy. Of interest, a distinct lymphoma other than DLBCL was identified in two of these cases. A false-positive radiological diagnosis of RT was rendered in two patients, including a case of Herpes simplex virus lymphadenitis. In conclusion, our findings confirm the central role of tissue biopsy in the diagnostic work up in case of clinically suspected RT.

https://ift.tt/2JKTpIJ

Congenital Myasthenic Syndromes in 2018

Abstract

Purpose of Review

Summarize features of the currently recognized congenital myasthenic syndromes (CMS) with emphasis on novel findings identified in the past 6 years.

Recent Findings

Since the last review of the CMS in this journal in 2012, several novel CMS were identified. The identified disease proteins are SNAP25B, synaptotagmin 2, Munc13-1, synaptobrevin-1, GFPT1, DPAGT1, ALG2, ALG14, Agrin, GMPPB, LRP4, myosin 9A, collagen 13A1, the mitochondrial citrate carrier, PREPL, LAMA5, the vesicular ACh transporter, and the high-affinity presynaptic choline transporter.

Summary

Exome sequencing has provided a powerful tool for identifying novel CMS. Identifying the disease genes is essential for determining optimal therapy. The landscape of the CMS is still unfolding.

https://ift.tt/2Juf6O2

Population Pharmacokinetics and Safety of Solithromycin Following Intravenous and Oral Administration in Infants, Children, and Adolescents [PublishAheadOfPrint]

Solithromycin is a novel fluoroketolide antibiotic, which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age 6 years [range 4 days - 17 years]) were administered intravenous (IV) or oral (capsules or suspension) solithromycin (IV 6-8 mg/kg; capsules/suspension 14-16 mg/kg on Day 1 and 7-15 mg/kg on Days 2-5). PK samples were collected after first and multi-dose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (N=13, median [range] age 16 years (12-17)) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and post-menstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg IV daily and oral dosing of 20 mg/kg on Day 1 (800 mg adult maximum) followed by 10 mg/kg on Days 2-5 (400 mg adult maximum) would achieve pediatric solithromycin exposure consistent with exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to study treatment.

https://ift.tt/2Jvxwhm

"Emergence of azole resistant Aspergillus fumigatus from immunocompromised hosts in India" [PublishAheadOfPrint]

This prospective study shows that the rate of azole resistant Aspergillus fumigatus (ARAF) in Indian immunocompromised patient population with invasive aspergillosis (IA) is low, 6/706 (0.8%). This lower rate supports the continued use of voriconazole as the first line of treatment. However, the ARAF in this study exhibited three kinds of unreported cyp51A mutations from India, of which two were at hot spots, G54R and P216L while one was at codon Y431C.

https://ift.tt/2LHNRvN

In vitro and in vivo Evaluation of APX001A/APX001 and other Gwt1 inhibitors against Cryptococcus [PublishAheadOfPrint]

Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here we evaluated the in vitro and in vivo activity of several compounds including APX001A and its prodrug APX001, currently in clinical development for invasive fungal infections. These compounds target the conserved Gwt1 enzyme that is required for the localization of glycosylphosphatidyl inositol (GPI)-anchored cell wall mannoproteins in fungi.

The Gwt1 inhibitors had low MIC values, ranging from 0.004 μg/mL to 0.5 μg/mL against both C. neoformans and C. gattii. APX001A and APX2020 demonstrated in vitro synergy with fluconazole (FICI 0.37). In a CM model, APX001 and fluconazole each, alone, reduced log₁₀ colony forming units (CFU)/g brain (0.78 and 1.04, respectively), whereas the combination resulted in a reduction of 3.52 log₁₀ CFU/g brain.

Efficacy as measured by a reduction in brain and lung fungal burden was also observed for another Gwt1 inhibitor prodrug, APX2096, where dose dependent reductions in fungal burden ranged between 5.91 and 1.79 log₁₀ CFU/g lung and between 7.00 and 0.92 log₁₀ CFU/g brain, representing near or complete sterilization of lung and brain tissue at the higher doses. These data support further clinical evaluation of this new class of antifungal agents for CM.

https://ift.tt/2sNxRBG

In Vitro activity of ceftazidime-avibactam against carbapenem-resistant and hypervirulent Klebsiella pneumoniae isolates [PublishAheadOfPrint]

Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains have emerged while antimicrobial treatment options remain limited. Herein, we tested the in vitro activity of ceftazidime-avibactam and other comparator antibiotics against 65 CR-hvKp isolates. Ceftazidime-avibactam, colistin and tigecycline are highly active in vitro against CR-hvKp isolates (MIC90 ≤ 1μg/ml), including KPC-2-producing ST11 CR-hvKp. Based upon previous clinical experience and the in vitro data presented herein, we posit that ceftazidime-avibactam is a considered therapeutic option against CR-hvKp infections.

https://ift.tt/2LKmSQb

Potency of solithromycin against fast and slow growing chlamydial organisms [PublishAheadOfPrint]

Evidence is provided that solithromycin is a bactericidal against not only fast growing chlamydial organisms but also those slowed by IFN in vitro. At sub-lethal concentrations, Sol impedes homotypic fusion of Chlamydia-containing vacuoles and reduces secretion of the type III secretion (T3S) effector, IncA. Sol may therefore represent a potential new clinical treatment for Chlamydia infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation.

https://ift.tt/2JuUgxJ

Colistin does not potentiate ceftazidime-avibactam killing of carbapenem-resistant Enterobacteriaceae in vitro or suppress emergence of ceftazidime-avibactam resistance [PublishAheadOfPrint]

We tested ceftazidime-avibactam and colistin against 24 carbapenem-resistant Enterobacteriaceae (CRE) by time-kills. Ceftazidime-avibactam (0.25x, 1x, 4x MIC) was bactericidal against 8%, 21%, and 88% of isolates, respectively. Colistin (2μg/mL) was bactericidal against 83% (12 hours) and 42% (24 hours) of isolates. In combination, synergy and antagonism was identified against 13% and 46% of isolates, respectively. The combination did not suppress ceftazidime-avibactam resistance. Colistin plus ceftazidime-avibactam did not provide benefit over ceftazidime-avibactam against most CRE isolates.

https://ift.tt/2LJdJrm

Phase I Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants (PROOF) [PublishAheadOfPrint]

The pharmacokinetics (PK), safety, and tolerability of two repeated dosing regimens of oral fosfomycin tromethamine were evaluated in 18 healthy adult subjects. Subjects received 3 g every other day (QOD) for 3 doses then every day (QD) for 7 doses, or vice versa, in a phase I, randomized, open-label, two-period crossover study. Serial blood (n=11) and urine samples (n=4 collection intervals) were collected before and up to 24 hours after dosing on Days 1 and 5 along with pre-dose concentrations on Days 3 and 7. PK parameters were similar between Days 1 and 5 within and between dosing regimens. The mean (±SD) PK parameters of fosfomycin in plasma on Day 5 during the QOD and QD dosing regimens, respectively, were: C_max= 24.4±6.2 vs 23.8±5.6 μg/mL, T_max= 2.2±0.7 vs. 2.0±0.4 h, V_d/F= 141±67.9 vs. 147±67.6 liters, CL/F= 21.4±8.0 vs. 20.4±5.3 liters/h, CL_R= 7.5±4.1 vs. 7.3±3.5 liters/h, AUC_0-24= 151.6±35.6 vs. 156.6±42.5 μg⋅h/mL, and t_1/2= 4.5±1.1 vs. 5.0±1.7 h. Urine concentrations peaked at approximately 600 μg/mL through the 0-8 hours urine collection intervals but displayed significant interindividual variability. Roughly 35-40% of the 3 g dose was excreted in the urine by 24 hours post-dose. No new safety concerns were identified during this study. The proportion of diarrhea-free days during the study was significantly lower in the QD regimen compared to the QOD regimen (61% vs. 77%, P<0.0001). Further studies establishing the clinical benefit:risk ratio of repeated dosing regimens of oral fosfomycin tromethamine are warranted.

https://ift.tt/2JwvkpR

Tet38 Efflux Pump Contributes to Fosfomycin Resistance in Staphylococcus aureus [PublishAheadOfPrint]

Fosfomycin inhibits MurA following uptake by the GlpT transporter of glycerol-3-phosphate in Escherichia coli. In Staphylococcus aureus, plasmid overexpression of the Tet38 efflux pump and a glpT mutant resulted in increased MICs and decreased accumulation of fosfomycin, with MICs affected by glycerol-3-phosphate. In contrast, a tet38 mutant had a lower MIC and increased accumulation of fosfomycin, suggesting that Tet38 acts as an efflux transporter of fosfomycin.

https://ift.tt/2LJeGQu

Biochemical and Structural Basis of Triclosan Resistance in a Novel Enoyl-Acyl Carrier Protein Reductase [PublishAheadOfPrint]

Enoyl-acyl carrier protein reductase (ENR), such as FabI, FabL, FabK and FabV, catalyzes the last reduction step in bacterial type II fatty acid biosynthesis. Previously, we reported metagenome-derived ENR homologs resistant to triclosan (TCL) and highly similar to 7-α hydroxysteroid dehydrogenase (7-AHSDH). These homologs are commonly found in Epsilonproteobacteria, a class that contains several human pathogenic bacteria, including the genera Helicobacter and Campylobacter. Herein, we report the biochemical and predicted structural basis of TCL resistance in a novel 7-AHSDH-like ENR. The purified protein exhibited NADPH-dependent ENR activity but no 7-AHSDH activity, despite its high homology with 7-AHSDH (69%-96%). Because this ENR was similar to FabL (41%), we propose that this metagenome-derived ENR is referred to as FabL2. Homology modeling, molecular docking, and molecular dynamic simulation analyses revealed the presence of an extrapolated six-amino acid loop specific to FabL2 ENR, which prevented the entry of TCL into the active site of FabL2 and was likely responsible for TCL resistance. Elimination of this extrapolated loop via site-directed mutagenesis resulted in the complete loss of TCL resistance but not enzyme activity. Phylogenetic analysis suggested that FabL, FabL2, and 7-AHSDH diverged from a common short-chain dehydrogenase reductase family. This study is the first to report the role of the extrapolated loop of FabL2-type ENRs in conferring TCL resistance. Thus, the FabL2 ENR represents a new drug target specific for pathogenic bacteria of Epsilonproteobacteria.

https://ift.tt/2sNxvuQ

Cis- and trans-acting factors influence expression of the norM-encoded efflux pump of Neisseria gonorrhoeae and levels of gonococcal susceptibility to substrate antimicrobials [PublishAheadOfPrint]

The gonococcal NorM efflux pump exports substrates with a cationic moiety including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The norM gene is part of a four gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (Ts) between the -10 and -35 hexamers; the majority of gonococcal strains analyzed herein contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly-T tract, the same transcriptional start site (TSS) was used for expression of norM. Interestingly, the T-6 tract correlated with a higher level of both norM expression and gonococcal resistance to NorM substrates BE and EB. Analysis of expression of genes downstream of norM showed that the product of the tetR-like gene has the capacity to activate expression of norM as well as murB, which encodes an acetylenolpyroylglucosamine reductase predicted to be involved in the early steps of peptidoglycan synthesis. Moreover, loss of the TetR-like transcriptional regulator modestly increased gonococcal susceptibility to NorM substrates EB and BE. We conclude that both cis- and trans-acting regulatory systems can regulate expression of the norM operon and influence levels of gonococcal susceptibility to antimicrobials exported by NorM.

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Multiple drug resistant Acinetobacter baumannii chloramphenicol resistance requires an inner membrane permease [PublishAheadOfPrint]

Acinetobacter baumannii is a Gram negative organism that is a cause of hospital acquired multidrug resistant (MDR) infections. A. baumannii has a unique cell surface compared to many other Gram-negative pathogens in that it can live without LPS and it has a high content of cardiolipin in the outer membrane. Therefore, to better understand the cell envelope and mechanisms of A. baumannii MDR, we screened a transposon library for mutants with defective permeability barrier function, as defined as a deficiency in the ability to exclude the phosphatase chromogenic substrate, 5-Bromo-4-chloro-3-indolyl phosphate (XP). We identified multiple mutants in the gene ABUW_0982, predicted to encode a permease broadly present in A. baumannii isolates, with increased susceptibility to the ribosome targeting antibiotic chloramphenicol (CHL). Moreover, when compared to other known CHL resistance genes such as chloramphenicol acyl-transferases, we find ABUW_0982 is the primary determinant of intrinsic CHL resistance in A. baumannii strain 5075, an important isolate responsible for severe MDR infections in humans. Finally, studies measuring the efflux of chloramphenicol and expression of ABUW_0982 in CHL-susceptible E. coli support the conclusion that ABUW_0982 encodes a single-component efflux protein with specificity for small, hydrophobic molecules, including CHL.

https://ift.tt/2JwMFyU

The Prevalence of a Cefazolin Inoculum Effect Associated with blaZ Gene Types Among Methicillin-Susceptible Staphylococcus aureus Isolates from Four Major Medical Centers in Chicago [PublishAheadOfPrint]

Cefazolin efficacy with high inoculum methicillin-susceptible Staphylococcus aureus (MSSA) infections remains in question due to therapeutic failure inferred from an inoculum effect. This study investigated the local prevalence of a cefazolin inoculum effect (CInE) and its association with staphylococcal blaZ gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, Illinois contributed MSSA isolates. Cefazolin MICs (C-MIC) were determined at 24 hours by broth microdilution method using standard inocula (SI, 5 x 10⁵ CFU/mL) and high inocula (HI, 5 x 10⁷ CFU/mL). The CInE was defined as 1) a ≥ 4-fold increase in C-MIC between SI and HI and/or 2) a pronounced CInE: a nonsusceptible C-MIC of ≥ 16 μg/mL at HI. PCR was used to amplify the blaZ gene, followed by agarose gel electrophoresis and sequencing to determine the gene type. Approximately 269 MSSA isolates were included. All but one isolate was susceptible to cefazolin at SI and 97% remained susceptible at HI. A total of 196 isolates (73%) were blaZ-positive, led by gene type C (40%). The CInE was seen in 45 blaZ-positive isolates (23%) with 44 (22%) presenting a ≥ 4-fold increase in C-MIC (SI to HI) and five (3%) with a pronounced CInE. Four out of the five, met both definitions of CInE with two expressing the type A gene. The prevalence of a pronounced CInE associated with the type A blaZ gene from MSSA isolates in Chicago is low. Our predilection for cefazolin use, even early in the management of hospitalized MSSA infections, is tenable.

https://ift.tt/2HDoAAF

Identification of 14 alpha-lanosterol demethylase (CYP51) in Scedosporium species [PublishAheadOfPrint]

Scedosporium spp. cause infections (scedosporiosis) in both immunocompetent and immunocompromised individuals and may persistently colonise the respiratory tract in patients with cystic fibrosis (CF). They are less susceptible against azoles when compared with other moulds such as Aspergillus, suggesting the presence of resistance mechanisms. It can be hypothesised that the decreased susceptibility of Scedosporium spp. to azoles is also CYP51 dependant. Analysis of the S. apiospermum and S. aurantiacum genome revealed one CYP51 gene encoding the 14 alpha-lanosterol demethylase. This gene of 159 clinical or environmental Scedosporium and three Lomentospora prolificans isolates has been sequenced and analysed. The Scedosporium CYP51 protein clustered with the group of known CYP51B orthologues and showed species-specific polymorphisms. A tandem repeat in the 5' upstream region of Scedosporium CYP51 like that in A. fumigatus could not be detected. Species-specific amino acid (aa) alterations in CYP51 of S. boydii, S. ellipsoideum, S. dehoogii and S. minutisporum isolates were located on positions that have not been described as having an impact on azole susceptibility. In contrast, two of the three S. apiospermum-specific aa changes (Y136F and G464S) corresponded to respective mutations in A. fumigatus CYP51A at aa position 121 and 448 (Y121F and G448S) that had been linked to azole resistance.

https://ift.tt/2Jvv4HE

Molecular confirmation of the linkage between Rhizopus oryzae CYP51A gene coding region and its intrinsic voriconazole and fluconazole resistance. [PublishAheadOfPrint]

Rhizopus oryzae is the most prevalent causative agent of Mucormycosis, an increasingly reported opportunistic fungal infection. These mucormycetes are intrinsically resistant to Candida- and Aspergillus-active antifungal azole drugs such as fluconazole and voriconazole, respectively. Despite of its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work is to establish if the Rhizopus oryzae CYP51 genes are the unique responsible for voriconazole and fluconazole intrinsic resistance in these fungal pathogens. Two CYP51 genes were identified in R. oryzae genome. We classify them as CYP51A and CYP51B based on their sequence similarity with other known fungal CYP51 genes. Later, we obtained a chimerical Aspegillus fumigatus strain harboring a functional R. oryzae CYP51A gene expressed under the regulation of wild type A. fumigatus CYP51A promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC-hypersusceptibility of the used A. fumigatus CYP51A deletant mutant as recipient strain. The A. fumigatus transformants harboring the R. oryzae CYP51A mimicked exactly the azole susceptibility patterns of this Mucormycete. The data presented in this work demonstrate that R. oryzae CYP51A coding sequence is the unique responsible of the R. oryzae azole susceptibility patterns.

https://ift.tt/2LKxizB

Risk factors for gastrointestinal colonization and acquisition of carbapenem-resistant Gram-negative bacteria among patients in intensive care units in Thailand [PublishAheadOfPrint]

This study was conducted to investigate the prevalence and risk factors for carbapenem-resistant Gram-negative Bacteria (CR-GNB) colonization and acquisition among patients admitted to Intensive Care Units (ICUs) in two tertiary care hospitals in Northern Thailand. Rectal swab screening for CR-GNB was performed on patients at ICU admission and discharge. Phenotypes and genotypes of all isolates were determined. Risk factors were analyzed by logistic regression analysis. Overall, carriage rates of CR-GNB at admission was 11.6% (32/275), mostly with Acinetobacter baumannii (n = 15) followed by Klebsiella pneumoniae (n = 9). The risk factor for CR-GNB colonization was hospitalization within the previous 6 months (P = 0.002). During ICU stay, the rate of CR-GNB acquisition was 25.2% (52/206), predominantly A. baumannii (n = 28) and K. pneumoniae (n = 13). Risk factors associated with CR-GNB acquisition were the use of enteral feeding tube (P = 0.008) and administration of third generation cephalosporins (P = 0.032) and carbapenems (P = 0.045). The most common carbapenemase genes in A. baumannii and K. pneumoniae were bla_OXA-23/51 and bla_NDM, respectively. Patient-to-patient transmission was demonstrated in three cases resulting in the acquisition of CR-A. baumannii spp. (2 cases) and K. pneumoniae (1 case) isolates from other patients who were admitted during the same period of time. This is the first Indochinese study screening patients and examining carriage of CR-GNB, and further demonstrating transfer of CR-GNB isolates in ICUs. Our study suggested that effective infection control measures are required to limit the spread of CR-GNB within the hospitals.

https://ift.tt/2sNQJQG

The effect of the novel antifungal drug F901318 (Olorofim) on the growth and viability of Aspergillus fumigatus [PublishAheadOfPrint]

F901318 (olorofim) is a novel antifungal drug that is highly active against Aspergillus species. Belonging to a new class of antifungals called the orotomides, F901318 targets dihydroorotate dehydrogenase (DHODH) in the de novo pyrimidine biosynthesis pathway. In this study, the antifungal effects of F901318 against Aspergillus fumigatus were investigated. Live-cell imaging revealed that, at a concentration of 0.1 μg/ml, F901318 completely inhibited germination, but conidia continued to expand by isotropic growth for >120 h. When this low F901318 concentration was applied to germlings or vegetative hyphae their elongation was completely inhibited within 10 h. Staining with the fluorescent viability dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC) showed that prolonged exposure to F901318 (>24 h) led to vegetative hyphal swelling and a decrease in hyphal viability through cell lysis. The time-dependent killing of F901318 was further confirmed by measuring fungal biomass and growth rate in liquid culture. Compared to the untreated control, the ability of hyphal growth to recover in drug-free medium after 24h exposure to F901318 was strongly impaired. A longer treatment of 48h further improved the antifungal effect of F901318. Together, the results of this study indicate that F901318 initially has a fungistatic effect on Aspergillus spp. isolates by inhibiting germination and growth, but prolonged exposure is fungicidal through hyphal swelling followed by cell lysis.

https://ift.tt/2LKx6An

Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics [PublishAheadOfPrint]

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor in development for use with other antiretroviral therapies to treat human immunodeficiency virus 1 (HIV-1) infection. Doravirine metabolism predominantly occurs via cytochrome P450 3A with <10% of elimination occurring via the renal pathway. As severe renal impairment can alter the pharmacokinetics (PK) of metabolically eliminated drugs, the effect of severe renal impairment on doravirine PK was assessed.

A single dose of doravirine 100 mg was administered to subjects aged 18–75 years with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m² (severe renal impairment group) and healthy controls with an eGFR of ≥80 mL/min/1.73 m², matched to the mean of the renal impairment group by age (±10 years) and weight (±10 kg). Doravirine plasma concentrations were determined at regular intervals and safety was monitored throughout.

The geometric mean ratios (90% confidence interval) for severe renal impairment/healthy subjects were 1.43 (1.00, 2.04), 1.38 (0.99, 1.92), and 0.83 (0.61, 1.15) for plasma doravirine area under the curve from zero to infinity (AUC_0–), plasma concentration at 24 hours post-dose (C₂₄), and maximum plasma concentration (C_max), respectively. Doravirine was generally well tolerated in both groups.

Based on the overall efficacy, safety, and PK profile of doravirine, the minor effect of severe renal impairment on doravirine PK observed in this study is not considered clinically meaningful.

https://ift.tt/2JyuCIN

Pembrolizumab exposure-response assessments challenged by association of cancer cachexia and catabolic clearance

Purpose: To investigate the relationship of pembrolizumab pharmacokinetics (PK) and overall survival (OS) in patients with advanced melanoma and non-small cell carcinoma (NSCLC). Experimental Design: PK dependencies in OS were evaluated across three pembrolizumab studies of either 200mg or 2-10 mg/kg Q3W. Kaplan-Meier (K-M) plots of OS, stratified by dose, exposure, and baseline clearance were assessed per indication and study. A Cox Proportional Hazards model was implemented to explore imbalances of typical prognostic factors in high/low NSCLC CL</SPAN>₀<SPAN style="font-family: Arial, sans-serif;"> subgroups. </SPAN>Results: <SPAN style="font-family: 'Arial','sans-serif';">1453 subjects were included, 340 with pembrolizumab-treated melanoma, 804 with pembrolizumab-treated NSCLC, and 309 with docetaxel-treated NSCLC. OS was dose-independent from 2-10 mg/kg for pembrolizumab-treated melanoma <SPAN style="background: white;">(</SPAN>HR=0.98; 95%CI, 0.94-1.02<SPAN style="background: white;">)</SPAN></SPAN> <SPAN style="font-family: 'Arial','sans-serif'; background: white;">and NSCLC (</SPAN><SPAN style="font-family: 'Arial','sans-serif';">HR=0.98; 95%CI, 0.95-1.01<SPAN style="background: white;">)</SPAN>; however, a strong CL₀-OS association was identified for both cancer types</SPAN> <SPAN style="font-family: 'Arial','sans-serif';">(unadjusted melanoma HR=2.56; 95%CI, 1.72-3.80 and NSCLC HR=2.64; 95%CI, 1.94-3.57). Decreased OS in subjects with higher pembrolizumab CL₀ paralleled disease severity markers associated with end-stage cancer-anorexia-cachexia syndrome. Correction for baseline prognostic factors did not fully attenuate the CL₀-OS association (multivariate-adjusted CL₀ HR=1.64; 95%CI, 1.06-2.52 for melanoma; HR=1.88; 95%CI, 1.22-2.89 for NSCLC). Conclusions: These data support the lack of dose or exposure dependency in pembrolizumab OS for melanoma and NSCLC between 2-10 mg/kg. An association of pembrolizumab CL₀ with OS potentially reflects catabolic activity as a marker of disease severity versus a direct PK-related impact of pembrolizumab on efficacy. Similar data from other trials suggest such patterns of exposure-response confounding may be a broader phenomenon generalizable to antineoplastic monoclonal antibodies.

https://ift.tt/2JQNGB0

The spatio-temporal evolution of lymph node spread in early breast cancer

Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derive from primary tumours. Experimental design: In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing (n=78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Results: Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken peri-operatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA. Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.

https://ift.tt/2HFrapQ

Integrated genomic classification of melanocytic tumors of the central nervous system using mutation analysis, copy number alterations and DNA methylation profiling

Purpose: In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria can be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Experimental Design: Targeted next-generation-sequencing, array-based genome-wide methylation analysis and BAP1 immunohistochemistry was performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, incl. 47 primary tumors of the central nervous system, 16 uveal melanomas. 13 cutaneous melanoma metastasis and 2 blue nevus-like melanomas. Gene mutation, DNA-methylation and copy-number profiles were correlated with clinicopathological features. Results: Combining mutation, copy-number and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas and blue nevus-like melanoma showed common DNA-methylation, copy-number alteration and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group. Conclusions: Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma and blue nevus-like melanoma share molecular similarity with chromosome 3 and BAP1 alterations markers of poor prognosis.

https://ift.tt/2JQNAt8

Evaluation of efficacy and safety of sorafenib in kidney cancer patients aged 75 years and older: a propensity score-matched analysis

Evaluation of efficacy and safety of sorafenib in kidney cancer patients aged 75 years and older: a propensity score-matched analysis

Evaluation of efficacy and safety of sorafenib in kidney cancer patients aged 75 years and older: a propensity score-matched analysis, Published online: 12 June 2018; doi:10.1038/s41416-018-0129-3

Evaluation of efficacy and safety of sorafenib in kidney cancer patients aged 75 years and older: a propensity score-matched analysis

https://ift.tt/2Midjcz

Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1c259T cells in Synovial Sarcoma [Research Articles]

We evaluated safety and activity of autologous T cells expressing NY-ESO-1c259, an affinity-enhanced T cell receptor (TCR) recognizing an HLA-A2-restricted NY-ESO-1/LAGE-1a-derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1c259T cells). Confirmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1c259T cells were present post-infusion in all patients and persisted for at least 6 months in all responders. Most infused NY-ESO-1c259T cells exhibited an effector memory phenotype following the ex vivo expansion, but the persisting pools comprised largely central memory and stem cell memory subsets, which remained polyfunctional and showed no evidence for T cell exhaustion despite persistent tumor burdens. Next generation sequencing of endogenous TCRs in CD8+ NY-ESO-1c259T cells revealed clonal diversity without contraction over time. These data suggest that regenerative pools of NY-ESO-1c259T cells produced a continuing supply of effector cells to mediate sustained, clinically meaningful antitumor effects.

https://ift.tt/2sNLpga

A Qualitative Analysis of Challenges and Successes in Retinopathy of Prematurity Screening

AJP Rep 2018; 08: e128-e133
DOI: 10.1055/s-0038-1660519

Objective The objective of this study is to identify characteristics of neonatal intensive care unit (NICU) practice that influence successful retinopathy of prematurity (ROP) screening. Study Design In this qualitative study, top, improved, and bottom performing NICUs in the California Perinatal Quality Care Collaborative were identified based on ROP screening rates and invited to participate. NICU personnel were interviewed using a semistructured questionnaire. Using thematic analysis, key factors that influence ROP screening were identified. Results Themes found in top performing hospitals include a commitment to quality improvement, a committed ophthalmologist, and a system of double checks. Improved NICUs had a common theme of utilizing telemedicine for exams and identification of eligible neonates on admission. The bottom performing hospital struggled with education and identification of eligible neonates and a lack of a dedicated ophthalmologist. Conclusion Structure, culture, education, and commitment all contribute to the success of ROP screening in the NICU.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Sonographic Estimated Fetal Weight among Diabetics at ≥ 34 Weeks and Composite Neonatal Morbidity

AJP Rep 2018; 08: e121-e127
DOI: 10.1055/s-0038-1660433

Objectives The objective was to assess the composite neonatal morbidity (CNM) among diabetic women with sonographic estimated fetal weight (SEFW) at 10 to 90th versus >90th percentile for gestational age (GA). Study Design The inclusion criteria for this retrospective study were singleton pregnancies at 34 to 41 weeks, complicated by diabetes, and that had SEFW within 4 weeks of delivery. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Results Among the 140 cohorts that met the inclusion criteria, 72% had SEFW at 10th to 90th percentile for GA, and 28% at >90th percentile. Compared with women with diabetes with last SEFW at 10th to 90th percentile, those with estimate > 90th percentile for GA had a significantly higher rate of CNM (13 vs. 28%; OR, 2.65; 95% CI, 1.07–6.59). Among 109 diabetic women who labored, the rate of shoulder dystocia was significantly higher with SEFW at >90th percentile for GA than those at 10th to 90th percentile (25 vs. 2%; p = 0.002); the corresponding rate of CNM was 29 versus 10% (p = 0.02). Conclusion Among diabetic women with SEFW > 90th percentile for GA, CNM was significantly higher than in women with estimate at 10 to 90th percentile. Despite the increased risk of CNM, these newborns did not have long-term morbid sequela.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

https://ift.tt/2HH5YzI

Certification Status Tied to Physician Performance Measures

MONDAY, June 11, 2018 -- Maintenance of certification (MOC) among physicians is associated with performance on selected Healthcare Effectiveness Data and Information Set (HEDIS) process measures, according to a study published online June 12 in the...

https://ift.tt/2JNOTck

Lengthy Viral Suppression May Cut Cancer Risk in HIV Infected

MONDAY, June 11, 2018 -- Antiretroviral therapy resulting in long-term viral suppression of HIV may contribute to cancer prevention, according to a study published online June 12 in the Annals of Internal Medicine. Lesley S. Park, Ph.D., M.P.H.,...

https://ift.tt/2HEGoeP

Kitchen Towels Are Source of Possibly Pathogenic Bacteria

MONDAY, June 11, 2018 -- Family composition and hygiene practices are associated with the microbial load of kitchen towels, according to a study presented at the annual meeting of the American Society for Microbiology, held from June 7 to 11 in...

https://ift.tt/2JHqYvn

CDC: Invasive MRSA More Likely Among Injection Drug Users

MONDAY, June 11, 2018 -- Injection drug users are more than 16-fold more likely to develop invasive methicillin-resistant Staphylococcus aureus (MRSA) infections, according to research published in the June 8 issue of the U.S. Centers for Disease...

https://ift.tt/2HJRcs8

Poor Social Network Adds Health Risks Across Cardiac Diagnoses

MONDAY, June 11, 2018 -- Having no one to talk to is associated with worse self-rated mental and physical health, anxiety, and depression among patients with cardiac diagnoses, according to a study presented at EuroHeartCare 2018, the European...

https://ift.tt/2JHoxJ4

The ulnar ratio as a sensitive and specific marker of acute inflammatory demyelinating polyneuropathy

Acute inflammatory demyelinating polyneuropathy (AIDP) is an acute demyelinating neuropathy classically defined as ascending paralysis associated with areflexia (Guillain et al., 1916). Sensory symptoms are common and occur early in the course of the disease, often before the onset of significant motor weakness. Diagnosis is based on a typical clinical picture, characteristic cerebrospinal fluid findings, and evidence of widespread demyelination on nerve conduction studies (NCS). The commonly used electrodiagnostic (EDX) criteria rely exclusively on the motor NCS findings (Ho et al., 1995, Hadden et al., 1998, Van Den Bergh et al., 2004) despite the widely recognized value of sensory abnormalities in the diagnosis of GBS (Albers et al., 1985, Gordon et al., 2001, Kuwabara et al., 2004, Al-Shekhlee et al., 2005, Al‐Shekhlee et al., 2007).

https://ift.tt/2sZdArX

Incidence Trends of Esophageal and Gastric Cancer Subtypes by Race, Ethnicity, and Age in the United States, 1997–2014

There is limited information on contemporary incidence rates and trends, by race, ethnicity, and age, for major subtypes of esophageal and gastric cancer in the United States. We examined the most recent nationwide incidence data for esophageal squamous cell carcinoma, esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) by race, ethnicity, and age in the United States.

https://ift.tt/2MinH41

Safety and Efficacy of Budesonide Oral Suspension Maintenance Therapy in Patients With Eosinophilic Esophagitis

We aimed to determine the safety and efficacy of budesonide oral suspension (BOS) maintenance therapy in patients with eosinophilic esophagitis (EoE).

https://ift.tt/2JGEonO

A rare case of hyperplastic proximal esophageal polyps with foveolar dysplasia

A 62-year-old male with long-standing esophageal reflux underwent endoscopy at an outside institution that reported multiple polypoid lesions in upper esophagus and a small focal area of nodular mucosa at the gastroesophageal junction(GEJ). Biopsies of the proximal esophageal polyps demonstrated hyperplastic mucosa with ulceration, reactive epithelial changes, and focal intestinal metaplasia. Biopsies from the nodular GEJ mucosa were described as Barrett's esophagus with low grade dysplasia.An upper endoscopy performed at our medical center found multiple semi-pedunculated esophageal polyps between 18-24 cm from the incisors (Figure A).Endosonographically the polypoid lesions were confined to the mucosa with normal underlying wall layers (Figure B).

https://ift.tt/2MkrnlD

Analysis of Fecal Primary Bile Acids Detects Increased Stool Weight and Colonic Transit in Patients with Chronic Functional Diarrhea

Patients with bile acid diarrhea (BAD) are identified based on increased levels of BAs in fecal samples collected over a 48-hr period while on a 100-gram fat diet (48-hr BA), retention of 75Se-labeled homocholic acid taurine, or serum levels of C4 or FGF19. BAD increases fecal weight and colonic transit. We investigated whether results of tests for BAD associate with increased fecal weight and more rapid colonic transit over a 24- or 48-hr period in patients with irritable bowel syndrome with diarrhea (IBS-D).

https://ift.tt/2t0W1Yn

Factors Associated With Recurrence of Barrett’s Esophagus After Radiofrequency Ablation

Radiofrequency ablation (RFA) is effective treatment for Barrett's esophagus (BE). However, some patients have recurrence after complete eradication of intestinal metaplasia (CEIM). We investigated the incidence of and factors associated with BE recurrence, with or without neoplasia, after RFA and CEIM using data from the national Veterans Affairs (VA) healthcare system.

https://ift.tt/2sOp7uP

Diagnosis and treatment of rumination syndrome

Rumination syndrome is a functional gastrointestinal disorder characterized by effortless post-prandial regurgitation. The disorder appears uncommon, although only limited epidemiological data are available. Awareness of the characteristic symptoms is essential for recognizing the disorder, and thus avoiding the long delay in diagnosis which many patients experience. Whilst objective testing by post-prandial esophageal high resolution impedance manometry is available in select referral centers, a clinical diagnosis can be made in most patients.

https://ift.tt/2JGyHqk

Maintenance Treatment of Eosinophilic Esophagitis With Swallowed Topical Steroids Alters Disease Course Over A 5-Year Follow-Up Period in Adult Patients

Although swallowed topical corticosteroids (STCs) are effective in inducing remission of active eosinophilic esophagitis (EoE), there are few data on maintenance of long-term remission. We evaluated the long-term effectiveness of STC therapy for adults with EoE.

https://ift.tt/2sQGNWJ

Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated With Clinical Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy

Levels of antibodies against the hepatitis B virus (HBV) core protein (anti-HBc) have been associated with response to nucleos(t)ide analogue and (peg)interferon therapy in patients with chronic HBV infection. We performed a prospective study to determine whether the total serum level of anti-HBc level (immunoglobulins M and G) is associated with clinical relapse after discontinuation of nucleos(t)ide analogue-based therapy.

https://ift.tt/2sZcWe1

Risk of Malignancy in Adenomas Detected During Screening Colonoscopy

A higher incidence of proximal interval cancers after colonoscopy has been reported in several follow-up studies. One possible explanation for this might be that proximally located adenomas have greater malignant potential. The aim of the present study was to assess the risk of malignancy in proximal versus distal adenomas in patients included in a large screening colonoscopy database; adenoma shape and the patients' age and sex distribution were also analyzed.

https://ift.tt/2MlhYKH

High prevalence of hepatic fibrosis, measured by Elastography, in a Population-based study of Mexican Americans

Hepatic fibrosis is a primary risk factor for cirrhosis and hepatocellular carcinoma, which affect a disproportionate number of Hispanics in the United States. We aimed to determine the prevalence of significant fibrosis, measured by point shear-wave elastography (pSWE), and determine characteristics of hepatic fibrosis and simple steatosis in a population-based study of Mexican American Hispanics in south Texas.

https://ift.tt/2JDsrPO

Identification of Feline Interferon Regulatory Factor 1 as an Efficient Antiviral Factor against the Replication of Feline Calicivirus and Other Feline Viruses

Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed. Further, we found that IRF1 was localized in the nucleus and efficiently activated IFN-β and the ISRE promoter. IRF1 can trigger the production of endogenous interferon and the expression of ISGs, suggesting that IRF1 can positively regulate IFN signalling. Importantly, the mRNA and protein levels of IRF1 were reduced upon FCV infection, which may be a new strategy for FCV to evade the innate immune system. Finally, the antiviral activity of IRF1 against feline panleukopenia virus, feline herpesvirus, and feline infectious peritonitis virus was demonstrated. These data indicate that feline IRF1 plays an important role in regulating the host type I IFN response and inhibiting feline viral infections.

https://ift.tt/2sQ9fYK

BRAFV600E Mutation Does Not Significantly Affect the Efficacy of Radioiodine Therapy in Patients With Papillary Thyroid Carcinoma Without Known Distant Metastases

Purpose The BRAFV600E mutation is the most common and specific oncogenic event in papillary thyroid carcinoma (PTC). However, its role in radioiodine therapy decision making has yet to be established. This study aimed to evaluate the impact of the BRAFV600E mutation on the clinical response to radioiodine therapy. Methods This retrospective study included PTC patients who received total thyroidectomy with lymph node dissection, radioiodine therapy, and thyroid-stimulating hormone suppression between January 2012 and March 2016. Included patients were divided into 2 groups based on the BRAF mutation status. The association between the clinicopathological characteristics and the BRAFV600E mutation was evaluated. After a median follow-up of 37 months, the clinical outcome between these 2 groups was also compared based on the ongoing risk stratification. Results A total of 512 PTC patients without distant metastases were included, with a positive BRAF mutation in 338 patients. No significant association was observed between the BRAF mutation and clinicopathological characteristics, except for sex, tumor size, and extrathyroidal extension. The initial risk stratification between the positive and negative mutation groups revealed no significant difference (P = 0.845). At the end of follow-up, no significant difference regarding the clinical response to radioiodine therapy was demonstrated between these 2 groups for all patients or patients with high recurrence risk (P = 0.586 and P = 0.680, respectively). Conclusions The BRAFV600E mutation status may not impact the clinical response to radioiodine therapy for PTC patients without distant metastases.

https://ift.tt/2sOrQoa

Two Different Causes of Decreased Activity on Ipsilateral Iliac Artery in Renal Transplant Scintigraphy

In 2 patients, perfusion images of renal transplant scintigraphy showed similarly decreased activity on ipsilateral iliac artery. One's graft was photopenic because of arterial thrombosis. However, the other's graft had sufficient perfusion and no abnormality in iliac arteries, but he had femoral arteriovenous graft for hemodialysis on the contralateral side. So, in this patient, decreased activity on ipsilateral iliac artery was probably related to increased arterial flow of the contralateral side. It should be considered that decreased activity on ipsilateral iliac artery in perfusion images is not only due to ipsilateral problem; the cause could be on the contralateral side.

https://ift.tt/2LK9pYD

Impact of Patient Age and Histological Type on Radioactive Iodine Avidity of Recurrent Lesions of Differentiated Thyroid Carcinoma

Background Age is a prognostic factor for recurrent differentiated thyroid carcinoma (DTC) and may be related to radioactive iodine (RAI) nonavidity. Indications for molecular-targeted drugs (MTDs) are currently limited to RAI-refractory DTC. Demonstrating refractoriness to RAI, mainly indicated by RAI nonavidity, may be a barrier to the introduction of MTDs for elderly patients. The present study was conducted to evaluate the impact of age and histological type on the RAI avidity of recurrent lesions of DTC. Methods Two hundred fifty-eight patients (189 patients with classic papillary thyroid carcinoma [cPTC], 8 patients with follicular variant of papillary thyroid carcinoma, and 61 patients with follicular thyroid carcinoma), who underwent their first RAI whole-body scanning for recurrent DTC at our institution between 2004 and 2013, were retrospectively studied. Radioactive iodine uptake was determined by visible uptake by metastatic lesion(s) in a diagnostic RAI–whole-body scan. Results The prevalence of RAI-avid lung metastases in cPTC indicated a significant, inverse correlation with age (

https://ift.tt/2sPSAVv

Incidental Detection of Meningioma by 18F-FMAU PET/CT in a Patient With Suspected Prostate Cancer

We report on an incidental detection of a meningioma on [18F]-2′-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (18F-FMAU) PET/CT scan that was performed during a prospective investigation of 18F-FMAU PET/CT for targeted biopsy of potential sites of tumor in men with suspected prostate cancer based on elevated prostate-specific antigen level. Neither prostate multiparamteric MRI nor 18F-FMAU PET/CT localized small volume Gleason 3 + 3 tumor deposits. However, an incidental focal high accumulation of 18F-FMAU was observed in high right parietal lobe that displayed characteristics of a meningioma on a subsequent brain MRI.

https://ift.tt/2LDu1li

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma

Aim In vivo pharmacokinetic analysis of [44Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [177Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [177Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Methods Pharmacokinetics of [44Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of 44Sc. Afterward, forward decay correction using the half-life of 177Lu was performed, extrapolating the pharmacokinetics of [44Sc]Sc-PSMA-617 to that of [177Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [177Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [177Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. Results The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body–absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). Conclusions [44Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [44Sc]Sc-PSMA-617 to that of [177Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [177Lu]Lu-PSMA-617.

https://ift.tt/2sNBbfM

Unicentric Castleman’s Disease Revealed by 18F-FDG PET/CT and Somatostatin Receptor Scintigraphy With 99mTc-HYNIC-TOC

A 51-year-old woman with a history of hypertension and abdominal pain was found with a retroperitoneal mass. The mass had intense enhancement in contrast-enhanced CT, and it showed a moderate degree of increased FDG uptake in PET/CT. The mass was also positive in somatostatin receptor scintigraphy with 99mTc-HYNIC-TOC, but it was negative in 131I-MIBG scan. The histopathological result after surgical resection of the mass confirmed the diagnosis of Castleman's disease, the hyaline vascular variant.

https://ift.tt/2LI5Br3

Quality and Safety in Health Care, Part XXXVII: More PINNACLE Registry Studies

Studies based on PINNACLE registry data include the management of high blood pressure, relationship of socioeconomic status and prescription practices, eligibility for medication therapy management programs, relationship of patient volume to adherence to guidelines, and relationship between quality and the type of provider. This article summarizes studies on all of those topics.

https://ift.tt/2sPS5uB

Peliosis Hepatis Simulating Metastatic Liver Disease on FDG PET/CT

A 20-year-old man with gastrointestinal symptoms and weight loss underwent FDG PET/CT, which revealed multiple hypermetabolic hepatic lesions concerning for metastatic liver disease. The outcome of liver biopsy was consistent with the diagnosis of peliosis hepatis which is a rare benign disease characterized by multiple blood-filled cystic spaces in the hepatic parenchyma. The findings of peliosis on FDG PET/CT are not well reported in the literature. These interesting images emphasize the importance of including peliosis hepatis in the differential diagnosis of multiple hypermetabolic hepatic lesions on FDG PET/CT, which could simulate malignancy.

https://ift.tt/2HDLojz

Growth Plate Suppression in an Adolescent Patient With Acute Lymphoblastic Leukemia After Treatment

Osteotoxic effect is a common adverse effect of chemotherapy for childhood acute lymphoblastic leukemia. The pathophysiology of impaired bone growth is multifactorial and can affect both osteoblast and osteoclast function. Significant contribution in affecting skeletal metabolism belongs to high-dose corticosteroid treatment. We present the case of a 12-year-old adolescent girl who was treated for high-risk pro-B acute lymphoblastic leukemia. The Tc-MDP bone scan, as a sensitive indicator of osteoblastic activity, shows that growth plate inhibition after intensive treatment may be temporary and reversible.

https://ift.tt/2Jwyiue

Sequential Sentinel Node Scintigraphy With Planar and SPECT/CT Images Revealed Contralateral Drainage From Ipsilateral Breast Tumor Relapse in a Patient With Bilateral Breast Cancer

Radio-guided sentinel node (SN) biopsy is routinely performed in patients with early breast cancer. However, repeated SN scintigraphy in ipsilateral breast tumor relapse (IBTR) often shows extra-axillary drainage, including contralateral axilla. A patient diagnosed with bilateral breast cancer, of which one was IBTR, was studied by sequential radio-guided SN mapping, radiocolloid injection to an IBTR breast and scanning, and then radiocolloid injection to the other breast and scanning. This revealed the lymphatic flow from the IBTR breast to the contralateral axilla. Sequential method may help to depict contralateral axillary lymphatic flow from an IBTR breast in patients with bilateral breast cancer.

https://ift.tt/2HHXt7p

Progression of Multiple Myeloma Detected on Cardiac Scintigraphy with 99mTc Sestamibi

It is important to understand normal and abnormal radiotracer biodistribution patterns in patients who undergo cardiac 99mTc-2-methoxyisobutyl-isonitrile (99mTc-sestamibi) scans to provide important clinical guidance. Our case describes a 75-year-old man with a history of multiple myeloma in remission, who presented to the emergency department for unrelated chest pain and shortness of breath. The patient underwent a nuclear cardiac stress test with 99mTc-sestamibi scintigraphy as part of his cardiac workup. The images demonstrated diffuse radiotracer uptake in the skeletal structures raising concern for progression of multiple myeloma, of which, subsequent biopsy confirmed the presence of recurrent disease.

https://ift.tt/2JwyedY

Fatal Intracranial Hemorrhage Due to Thrombocytopenia in a Patient With Castration-Resistant Prostate Cancer Showing Extensive Bone Uptake of Injected 223Ra Dichloride

A 64-year-old man with castration-resistant prostate cancer received 223Ra injection to treat bone metastases. The patient underwent a 223Ra SPECT scan after the first 223Ra injection in which there was increased uptake all over the spine. Spine-to-background activity ratio in the patient was approximately three times greater than normal spine-to-background activity ratios in 223Ra SPECT obtained from the other patients. Eight days after the fifth injection, the patient exhibited a very poor neurologic examination and died of intracranial hemorrhage due to severe thrombocytopenia (platelet counts, 23,000/mm3). The extensive radiation to the spine may have enhanced myelophthisic process in this case.

https://ift.tt/2HGPjMA

Capillary Hemangioma as an Unusual Cause of Doughnut Sign on Bone Scan

Abstracts A 28-year-old woman presented with a mass in her right leg, which, on plain radiograph, appeared as a lytic lesion in the mid-shaft of the tibia with cortical thinning but without periosteal reaction. 99mTc-MDP 3-phase bone scan demonstrated intense uptake in the periphery of the mass with a photopenic center, the so-called doughnut sign. Histopathology revealed a capillary hemangioma. This case demonstrates that the doughnut sign on bone scan can be caused by capillary hemangioma in addition to other reported bone pathologies, including aneurysmal bone cyst, giant cell tumor, and telangiectatic osteosarcoma.

https://ift.tt/2JwyauK

Solitary Breast Metastasis From Rhabdomyosarcoma Shown on FDG PET/CT

Rhabdomyosarcoma rarely metastasizes to breast. A 15-year-old adolescent girl underwent FDG PET/CT scan for staging a newly diagnosed alveolar rhabdomyosarcoma. The images showed not only the abnormal activity in the region of the right maxillary sinus, consistent with the known primary tumor, but also an intense focal activity in the right breast. The right breast lesion was excised, and the pathological results showed alveolar rhabdomyosarcoma.

https://ift.tt/2HJnbZc

Adrenal Histoplasmosis

An 89-year-old woman presented with seizure and hyponatremia. CT and MRI demonstrated mass-like enlargement of the adrenal glands and multiple pulmonary nodules. PET/CT performed to evaluate for metastatic disease demonstrated intense 18F-FDG uptake within enlarged adrenal glands. Given mild uptake in the pulmonary nodules, the differential diagnosis for the adrenal uptake included lymphoma, granulomatous infection, and less likely, metastatic lung cancer.

https://ift.tt/2Jvjkoy

Diagnostic Performance of 18F-Fluciclovine in Detection of Prostate Cancer Bone Metastases

Purpose 18F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for PET imaging in men with biochemical recurrence (BCR) of prostate cancer after prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer. Methods We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of 18F-fluciclovine PET/CT in an attempt to draw practical and general conclusions on the utility and limitations of 18F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer. Results The cumulative preclinical data and results of some retrospective and 2 prospective clinical studies suggest that 18F-fluciclovine can detect early bone marrow involvement in patients with BCR of prostate cancer and negative prior bone-specific imaging findings. Conclusions 18F-fluciclovine PET/CT seems to offer useful information for early detection of bone metastases in men with BCR of prostate cancer. Additional investigations will be needed to compare the diagnostic performance of 18F-fluciclovine PET/CT to other standard and novel imaging methods in initial staging, BCR, and castrate-resistant phases of disease.

https://ift.tt/2LFVhQe

Temporal Uptake Patterns of 18F-Fluorocholine Among Hyperfunctioning Parathyroid Glands

Optimal scan time of 18F-fluorocholine (FCH) PET/CT for localization of hyperfunctioning parathyroid glands is poorly documented. We report a small series of 9 histologically proven hyperfunctioning parathyroid gland with heterogeneous temporal uptake profile. Thirty-minute dynamic acquisition starting just after 18F-fluorocholine administration and delayed acquisition were recorded. Three different uptake patterns are seen (early washout, stable uptake, late increase) indicating the importance of an early (5–10 minutes) acquisition. A late acquisition (60 minutes) could be useful when the early acquisition is negative. No correlations were noted between uptake profile and histological or genetic results.

https://ift.tt/2sPOL2w

Mixed Epithelial and Stromal Tumor of the Kidney Mimicking Malignancy on 18F-FDG PET/CT in a Patient With Breast Cancer

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare renal tumor composed of solid and cystic components. Mixed epithelial and stromal tumor of the kidney has no pathognomonic imaging feature. It is difficult to distinguish MESTK from other cystic renal neoplasms using current radiological methods. We report a rare case of MESTK that was diagnosed in a 46-year-old woman with breast cancer. 18F-FDG PET/CT and contrast-enhanced CT features of MESTK are presented, which could potentially provide useful information in the differential diagnoses of cystic renal neoplasms.

https://ift.tt/2HGBPAo

Impressive Response to Tandem Treatment With [90Y]DOTATOC and [177Lu]DOTATOC in Grade 3 Pancreatic Neuroendocrine Carcinoma

Peptide receptor radionuclide therapy is an effective, well-tolerated, treatment for well-differentiated neuroendocrine tumors, resulting in a significant survival benefit and improvement of quality of life. Very few data are available on peptide receptor radionuclide therapy effectiveness in grade 3 neuroendocrine carcinomas with high somatostatin receptor expression. We report the case of a 70-year-old woman with metastatic pancreatic grade 3 neuroendocrine carcinoma who underwent 6 cycles of tandem treatment with investigational radiopharmaceuticals 90Y-DOTATOC and 177Lu-DOTATOC achieving an impressive response.

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Combined [18F]-Fluoroethylcholine PET/CT and 99mTc–Macroaggregated Albumin SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular Carcinoma

Aim The aim of this study was to retrospectively analyze the prognostic value of combined 99mTc–macroaggregated albumin (MAA) SPECT/CT and [18F]-fluoroethylcholine (FEC) PET/CT before radioembolization for survival of patients with intermediate-stage hepatocellular carcinoma. Methods Twenty-four patients with known hepatocellular carcinoma Barcelona Clinic Liver Cancer stage B were eligible for this analysis. All patients were scheduled for radioembolization and received a pretherapeutic [18F]FEC PET/CT scan as well as 99mTc-MAA SPECT/CT for hepatopulmonary shunting. Laboratory and semiquantitative PET parameters and morphologic and metabolic (intersection) volumes of MAA and FEC were evaluated. Spearman correlation with overall survival, receiver operating curve analyses, univariate and multivariate Cox regression, and Kaplan-Meier-analysis was applied. Results All patients (5 female/19 male) are deceased within the observational period. Median survival was 395 days (±51 days; range, 23–1122 days). The percentage of hypervascularized metabolically active tumor volume (vascularized tumor ratio; defined as high MAA and FEC uptake) correlated significantly with survival. Vascularized tumor ratio was a significant predictor in univariate and multivariate analyses (P = 0.026; hazard ratio, 11.65; 95% confidence interval, 1.62–83.73; P = 0.015). Statistical significance was not reached by all other variables in multivariate analysis. Receiver operating curve analysis for 1-year survival revealed an area under the curve of 0.77 (P = 0.024) for vascularized tumor ratio. At a cutoff value of 9%, sensitivity, specificity, and positive and negative prediction were 83%, 67%, and 71% and 80% (P = 0.036). Patients with a higher tumor vascularization had a median survival of 274 ± 80 versus 585 ± 284 days (P = 0.015). Conclusions Hepatocellular carcinoma with high vascularization in metabolic active areas as assessed by combined FEC PET/CT and Tc-MAA SPECT/CT represents an unfavorable subgroup with reduced overall survival after radioembolization.

https://ift.tt/2HHPAyJ

The Impact of the effectiveness of GATA3 as a prognostic factor in breast cancer

The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semi-quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR), quantitative real-time PCR carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n=25).

https://ift.tt/2l3dQm8

Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front

Accurate prediction of regional lymph node metastases (LNM) in endoscopically resected pT1 colorectal cancer (CRC) is crucial in treatment stratification for subsequent radical surgery. Several miRNAs have been linked to CRC invasion and metastasis, including the oncogenic miR-17/92 cluster, and expression levels might have predictive value in the risk assessment of early metastatic progression in CRC. We performed global miRNA microarray using tissue samples from the invasive front of pT1 CRC and investigated associations of the miR-17/92 cluster and presence of LNM.

https://ift.tt/2y3zWhT

Desmoplastic non- infantile astrocytoma/Ganglioglioma: rare low-grade tumor with frequent BRAF V600E mutation

Desmoplastic Infantile Astrocytoma/Ganglioglioma (DIA/DIG) are rare primary glioneuronal tumors that comprise 0.5–1.0% of all intracranial tumors. While BRAF mutation is found in up to 50% of pediatric gangliogliomas, data for DIA/DIGs is limited. This study was carried out to evaluate the frequency of BRAF V600E mutation in DIA/DIG. All cases of DIA/DIGs diagnosed over 7years (2010–2016) were reviewed retrospectively. The clinical, radiological and histopathological characteristics of these patients were evaluated along with immunohistochemical analysis for glial and neuronal markers.

https://ift.tt/2l4E3ke

Lymphomas with pseudo-double hit BCL6-MYC translocations due to t(3;8)(q27;q24) are associated with a germinal center immunophenotype, extranodal involvement, and frequent BCL2 translocations

High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, "double hit" or "triple hit" lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique "pseudo-double hit" BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed.

https://ift.tt/2y2jXR8

Androgen receptor expression is a favorable prognostic factor in triple-negative breast cancers

Androgen receptor (AR) expression is an emerging prognostic marker that has been observed in 25% to 75% of triple negative breast cancers (TNBCs) that lack estrogen receptor, progesterone receptor and HER2 overexpression. TNBCs are treated with AR-targeted therapies and standardized evaluation of AR expression may help guide patient management. Basal-like TNBCs are a subgroup of TNBCs defined by positive immunoreactivity for CK5/6 or EGFR that carry a worse prognosis. However, it's unclear whether basal-like TNBCs have a different rate of AR positivity or if AR expression is predictive of disease free survival in this patient group.

https://ift.tt/2l77CBD

The role of age in pancreatic Intraductal Papillary Mucinous Neoplasms of the Pancreas: same risk of death but different implications for management

Current guidelines do not address the role of age in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.

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Breaking bad news: how to cope

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PC-FACS June 4, 2018

Chemotherapy-Induced Peripheral Neuropathy

https://ift.tt/2JLBemc

Inter-rater agreement of intensivists evaluating the goal-concordance of preference-sensitive ICU interventions

Goal-concordant care has been identified as an important outcome of advance care planning and shared decision-making initiatives. However validated methods for measuring goal-concordance are needed.

https://ift.tt/2HGFwpO

Resource use during the last 6 months of life among COPD patients: a population level study

Chronic obstructive pulmonary disease (COPD) patients often have several comorbidities, such as cardiovascular diseases (CVD) or lung cancer (LC), which might influence resource use in the final months of life. However, no previous studies documented resource use in end-of-life COPD patients at a population level, thereby differentiating whether COPD patients die of their COPD, CVD or LC.

https://ift.tt/2JLrPef

Role of daily plan adaptation in MR-guided stereotactic ablative radiotherapy for adrenal metastases

Stereotactic ablative radiotherapy (SABR) delivered during shallow inspiration breath-hold under MR-guidance, was implemented for adrenal gland metastases. We studied inter-fractional changes in GTV and OARs, and also the role of online plan re-optimization in ensuring both adequate target coverage and OAR sparing. Online plan adaptation led to improved target coverage in 63% of treatment fractions, and significantly reduced OAR doses. Our results indicate that online plan adaptation is beneficial in adrenal SABR.

https://ift.tt/2Jr36fY

Programmatic comparison and dissemination of an audit of single fraction radiotherapy prescribing practices for bone metastases is associated with a meaningful and lasting change in practice on a population level

After an audit-based educational intervention in our population-based provincial radiotherapy program, we demonstrate a lasting and meaningful 10% increase in the prescription of SFRT for bone metastases. Other jurisdictions should consider using similar programmatic audit-based educational approaches in an effort to increase the use of this cost-effective treatment which has been historically used well below evidence-based benchmarks internationally. Our data suggests that the benchmark of 60% use of SFRT for bone metastases is feasible.

https://ift.tt/2JyCaHc

Volcanoes

A calm peacefulness, a chaotic mess, a tranquil ending. That is how I would describe the connection between my images of volcanoes and my experience with kidney disease.

https://ift.tt/2LKSc1A

Adenomyomatosis of the Gallbladder as a Cause of Recurrent Abdominal Pain

A 14-year-old girl was admitted for evaluation of recurrent abdominal pain lasting for 3 months. Pain episodes were described as severe, colicky, and umbilical; they occurred mainly during the day, but were also associated with repeated nocturnal awakenings, with no nausea, vomiting, or diarrhea. There was no history of fever, blood or mucus in the stools, constipation, anorexia, or weight loss.

https://ift.tt/2JL79TD

Pediatric Nonalcoholic Fatty Liver Disease in New York City: An Autopsy Study

To assess the prevalence and severity of nonalcoholic liver disease (NAFLD) in children in a diverse population sample in New York City.

https://ift.tt/2LH4hoc

Rapid-Fire

Hypercalcemia is commonly encountered in the clinical setting and requires identification by the clinician to avoid disastrous patient outcomes. The 2 most common causes are malignancy and hyperparathyroidism. The underlying cause for hypercalcemia may be readily known at presentation or may require further investigation. After identification, acuity of treatment will depend on severity of calcium level and symptoms. In the emergency setting, intravenous hydration with isotonic fluids is the treatment mainstay. Other commonly used medications to further decrease calcium include bisphosphates, calcitonin, steroids, and (rarely) furosemide. In life-threatening circumstances, dialysis can be implemented.

https://ift.tt/2JywaOG

Rapid Fire: Pericardial Effusion and Tamponade

One of the most common causes of pericardial effusion in the Western world is malignancy. Emergency physicians must maintain vigilance in suspecting pericardial effusion and tamponade in patients with known or suspected malignancy who present with tachycardia, dyspnea, and hypotension. Diagnosis can be expedited by key physical examination, electrocardiogram, and sonographic findings. Unstable or crashing patients with tamponade must undergo emergent pericardiocentesis for removal of fluid and pressure to restore cardiac output.

https://ift.tt/2sQqSaV

Pediatric Oncologic Emergencies

Pediatric patients with cancer, although rarely, do present to emergency departments for first-time diagnosis, as well as for complications of treatment. The presenting symptoms can be vague, so emergency physicians must maintain a high index of suspicion and be aware of guidelines to help direct appropriate care after an initial diagnosis. It is also necessary to know the complications of treatment. Although these patients often seek care in the institution where they receive treatment, many live far from these locations and may present to any emergency department in extremis.

https://ift.tt/2t1n59U

Rapid-Fire: Acute Blast Crisis/Hyperviscosity Syndrome

Emergency providers are likely to encounter patients with acute and chronic leukemias. In some cases, the first presentation to the emergency department may be for symptoms related to blast crisis and leukostasis. Making a timely diagnosis and consulting a hematologist can be life saving. Presenting symptoms are caused by complications of bone marrow infiltration and hyperleukocytosis with white blood cell counts over 100,000. Presentations may include fatigue (anemia), bleeding (thrombocytopenia), shortness of breath, and/or neurologic symptoms owing to hyperleukocytosis and subsequent leukostasis. Treatment of symptomatic cases involves induction chemotherapy and/or leukapheresis. Asymptomatic hyperleukocytosis can be treated with hydroxyurea.

https://ift.tt/2sN9RP6

The Latest Cancer Agents and Their Complications

The latest cancer agents, collectively known as cancer immunotherapy, have tremendously increased the armamentarium against cancer. Their targeted mechanisms seem ideal, but they do come with complications. As these therapies become more widespread, emergency physicians everywhere must be aware of the immune-related adverse events that can occur, and be ready to identify and coordinate treatment. This article provides the emergency physician with a brief introduction and overview of immunotherapy drugs and their complications.

https://ift.tt/2JAmxPC

Infectious Disease Emergencies in Patients with Cancer

Patients with cancer can be immunocompromised because of their underlying malignancy as well as the medical therapies with which they are treated. Infections frequently present atypically and can be challenging to diagnose. The spectrum of infectious diseases encountered in patients receiving chemotherapy, hematopoietic stem cell transplant, and immunotherapy is broad depending on the depth of immunosuppression. Early recognition of infectious processes followed by appropriate diagnostic testing, imaging, and empiric antibiotic therapy in the emergency department are critical to providing optimal care and improving survival in this complex patient population.

https://ift.tt/2sP9Km6

Fludarabine and busulfan plus low-dose TBI as reduced intensity conditioning in older patients undergoing allogeneic hematopoietic cell transplant for myeloid malignancies

Abstract

We have been using a combination of fludarabine/busulfan plus low-dose total body irradiation (TBI) as the reduced-intensity conditioning (RIC) regimen for patients age ≥ 60 years undergoing allogeneic hematopoietic cell transplantation (HCT) for myeloid malignancies. We retrospectively analyzed outcomes of 116 older patients (median age 64 years) who underwent HCT from 2006 to 2015 for myeloid malignancies, including acute myeloid leukemia (AML) in first complete remission (CR1). On univariate analysis, overall survival (OS) for the cohort at 3 years was 33% (95% CI 25–42). Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 3 years were 24% (95% CI 16–32) and 43% (95% CI 34–52), respectively. Multivariable analysis for OS demonstrated AML patients to have superior outcome (HR 1.60 for other myeloid, 95% CI 1.01–2.54, p = 0.045), as well as related donors (HR 1.92 for unrelated, 95% CI 1.22–3.03, p = 0.005). For NRM, AML patients had superior outcome (HR 1.76 for other myeloid, 95% CI 1.03–3.01, p = 0.038), as well as patients with related donors (HR 1.81 for unrelated, 95% CI 1.07–3.07, p = 0.028). We then demonstrated that AML patients with related donors (n = 45) had superior 3-year OS of 51% (95% CI 36–65), compared to 21% (95% CI 12–32) for all other patients (p = 0.0003). We conclude that the RIC regimen used is effective for older patients, particularly AML patients in CR1 with matched related donors.

https://ift.tt/2MlSY5U