Pembrolizumab-induced Sarcoid-like Reactions during Treatment of Metastatic Melanoma.

Pembrolizumab is a programmed cell death protein 1, or PD-1, inhibitor therapy immunotherapy for patients with advanced melanoma. This report discusses a series of documented cases of sarcoid-like reactions associated with this therapy. Three patients with malignant melanoma developed metastatic disease and were treated with pembrolizumab immunotherapy. Subsequent imaging showed lymphadenopathy in the mediastinum and hilar regions that was confirmed to represent a sarcoid-like reaction at histologic examination. Radiologists should be aware of the association between pembrolizumab and the development of sarcoid-like reactions to avoid inaccurately ascribing these imaging findings to metastatic disease. Clinical presentation, biopsy, radiographic evidence of bilateral hilar lymphadenopathy (with paratracheal lymphadenopathy), and elevated serum angiotensin-converting enzyme levels aid in the diagnosis of sarcoid-like reactions and help avoid these reactions being mistaken for recurrent or metastatic disease.

Horizon scanning for invasive alien species with the potential to threaten biodiversity in Great Britain.

Invasive alien species (IAS) are considered one of the greatest threats to biodiversity, particularly through their interactions with other drivers of change. Horizon scanning, the systematic examination of future potential threats and opportunities, leading to prioritization of IAS threats is seen as an essential component of IAS management. Our aim was to consider IAS that were likely to impact on native biodiversity but were not yet established in the wild in Great Britain. To achieve this, we developed an approach which coupled consensus methods (which have previously been used for collaboratively identifying priorities in other contexts) with rapid risk assessment. The process involved two distinct phases: Preliminary consultation with experts within five groups (plants, terrestrial invertebrates, freshwater invertebrates, vertebrates and marine species) to derive ranked lists of potential IAS. Consensus-building across expert groups to compile and rank the entire list of potential IAS. Five hundred and ninety-one species not native to Great Britain were considered. Ninety-three of these species were agreed to constitute at least a medium risk (based on score and consensus) with respect to them arriving, establishing and posing a threat to native biodiversity. The quagga mussel, Dreissena rostriformis bugensis, received maximum scores for risk of arrival, establishment and impact; following discussions the unanimous consensus was to rank it in the top position. A further 29 species were considered to constitute a high risk and were grouped according to their ranked risk. The remaining 63 species were considered as medium risk, and included in an unranked long list. The information collated through this novel extension of the consensus method for horizon scanning provides evidence for underpinning and prioritizing management both for the species and, perhaps more importantly, their pathways of arrival. Although our study focused on Great Britain, we suggest that the methods adopted are applicable globally.

Modification of the explant system for the removal of well fixed hip resurfacing sockets.

A major concern during revision hip arthroplasty is acetabular bone loss during the extraction of well-fixed acetabular components. Despite the good early survivorship of resurfacing prostheses, revision surgery may be necessary. We recommend the use of the Explant acetabular extraction system (Zimmer, Warsaw, Ind) with a trial liner to preserve acetabular bone stock. We present 2 cases of revised resurfacings using this technique, demonstrating minimal interference to the remaining acetabular bone.

Diagnosis of acute HIV infection in Connecticut.

Acute HIV infection (AHI) is the earliest stage of HIV disease, when plasma HIV viremia, but not HIV antibodies, can be detected. Acute HIV infection often presents as a nonspecific viral syndrome. However, its diagnosis, which enables linkage to early medical care and limits further HIV transmission, is seldom made. We describe the experience of Yale's Center for Interdisciplinary Research on AIDS with AHI diagnosis in Connecticut, as a participating center in the National Institute of Mental Health Multisite AHI Study. We sought to identify AHI cases by clinical referrals and by screening for AHI at two substance abuse care facilities and an STD clinic. We identified one case by referral and one through screening of 590 persons. Screening for AHI is feasible and probably cost effective. Primary care providers should include AHI in the differential diagnosis when patients present with a nonspecific viral syndrome.

An unusual trophic subsidy and species dominance in a tropical stream.

In classical theory, species are assumed to achieve dominance through competitive exclusion, but if food resources are limiting, cross-habitat trophic subsidies could also underpin dominance. The impact of dominant species on community dynamics may depend on the energy base of population size. We report on an unusual, spatially subsidized population of a tropical, stream-dwelling crab that dominates the benthic fauna of a Kenyan stream. Diet and stable isotope analyses indicated that this crab is a true omnivore, with terrestrial subsidies dominating both plant and animal resources. Unusually, the animal prey included almost no aquatic invertebrates. Instead, a single species of ant constituted approximately 35% of the annual diet (stomach contents analysis) and up to 90% of assimilated nitrogen (estimates from stable isotope analysis). Ants may be pivotal to enabling crab dominance, and this crab may be largely disconnected from the local trophic network for its dietary needs. The paucity of other invertebrates in the stream community suggests that this super-dominant crab is a strong interactor that suppresses aquatic invertebrate populations. Common stabilizing attributes of spatially subsidized food webs (e.g., asynchronous prey availability, wide feeding niche, consumer migration) were absent from this system, and although apparently stable, it may be vulnerable to disturbance in the donor habitat.

Suggested spontaneous resolution of possible paediatric hydrosalpinx: a case report with discussion.

Hydrosalpinx is a rare cause of abdominal pain in paediatric patients, though cases are documented in the literature. Its aetiology differs considerably from traditional hydrosalpinx due to ascending sexually transmitted infection. Hydrosalpinx can resent mimicking an acute abdomen or can be asymptomatic. Management of paediatric hydrosalpinx varies but often involves surgical removal of the affected tube. A 12-year-old girl presented with left-sided acute abdominal pain setting within 24 h. Initial ultrasound scan suggested presence of hydrosalpinx. Post-discharge follow-up appointment with a consultant paediatric gynaecologist demonstrated no symptomology, but repeated scan by another sonographer showed continued presence of possible hydrosalpinx, which had since grown. Later, MRI was performed to confirm site of the lesion. However, MRI revealed no tubal masses, suggesting spontaneously resolved hydrosalpinx. Consultant-administered ultrasound scan confirm no tubal abnormalities. Our case suggests spontaneous resolution in possible paediatric hydrosalpinx. Our recommendation is for conservative management of asymptomatic paediatric and adolescent hydrosalpinges, with emergency surgery offered if symptoms indicative of tubal or adnexal torsion.

Imaging evaluation of treated benign bone tumours.

A number of benign bone tumours can be treated with curettage and packing with either bone cement or graft. It is essential that the radiologist be familiar with both the normal and abnormal post-operative imaging appearance of these treated tumours. Through the use of numerous imaging examples, we aim to provide a pictorial review of the expected post-operative appearance of benign bone tumours treated with curettage and packing, as well as the imaging features of recurrence, the most common potential complication.

Accommodative responses to chronic irradiation: effects of dose, dose rate, and pharmacological response modifiers.

Low-level radiation exposures are expected to have long-term health implications but few near-term effects that would impair function. These assumptions are based on extrapolation from acute exposure responses, not on studies of a larger array of exposure scenarios (e.g., protracted exposures) that might present as operational threats. Protracted exposure is one scenario that needs to be better defined in terms of both the initial effect and the long-term health consequences. Reported here are the near-term effects of chronic, low daily-dose gamma-irradiation (3-128 mGy per day) on the blood-forming system of canines. Change in hematopoietic capacity was monitored along with time of exposure and cumulative radiation dose. The rate, magnitude, and timing of suppression and accommodation were determined. The ability of periodic treatment with a lipopolysaccharide immunomodulator to alleviate the suppressive hematopoietic effects of chronic exposure was tested. The effects of other pharmacologics (amifostine, granulocyte colony-stimulating factor, cytokine) are projected on the basis of current research using rodent models. Results indicated that low but significant suppression of blood leukocyte and platelet levels occurred at 3 mGy per day. As the dose rate increased from 3 mGy to 128 mGy per day, the rate of suppression increased approximately eightfold, whereas the time to accommodate declined from 2,000 days to approximately 150 days. Within the time frame required to reach the upper limit of 700 mGy, none of the dose rates examined elicited blood cell decrements large enough to severely compromise near-term immune function. Pharmacological intervention with lipopolysaccharide minimized hematopoietic suppression in only a small fraction of the treated animals that displayed distinctive long-term survival and pathology patterns. Comparable short-term benefits of treatment with hematopoietic cytokines or chemoprotectants are predicted on the basis of responses noted in rodent models. Long-term benefits of such treatments remain to be determined. Future work will require the application of advanced molecular tools to more fully assess potential pathophysiological responses and their modulation after low-level radiation exposure.

Interphalangeal joint involvement of the big toe in gout: a rare presentation.

Atypical presentation of gout can cause diagnostic dilemmas. We report a case of gout that presented with an expansile lytic lesion involving the interphalangeal joint of the hallux, lack of a history of gout, and an associated solitary lung nodule. Magnetic resonance imaging showed an expansile destructive bony lesion with soft-tissue involvement suggestive of a possible bony metastasis. A needle biopsy was performed, and histopathologic features were diagnostic of chronic tophaceous gout.

Opinion: Labour Analgesia in the Developing World; Why Not.

The provision of western-style safe, highly effective labour analgesia requires levels of training, staffing and technology that make its applicability in the developing world in current circumstances questionable. This review examines the reasons.

Radiographic structural abnormalities associated with premature, natural hip-joint failure.

BACKGROUND: Significant controversy exists regarding the causes of premature, natural hip-joint failure. Identification of these causes may guide future investigations targeting prevention of this disorder. The aims of this study were to: (1) determine and characterize structural abnormalities associated with premature, natural hip-joint failure, and (2) analyze disease progression in the contralateral hips of patients with femoroacetabular impingement deformities. METHODS: We analyzed 604 patients (710 hips) from three different medical centers who underwent primary total hip arthroplasty at or before fifty years of age (average age, forty years). Three hundred fourteen patients (52%) were male, and 290 patients (48%) were female. RESULTS: The diagnoses associated with premature hip failure varied, but osteoarthritis and osteonecrosis were most common. Radiographic abnormalities associated with developmental hip dysplasia and femoroacetabular impingement were associated with the majority of osteoarthritic hips. Hips with femoroacetabular impingement deformities demonstrated distinct structural anatomy relative to asymptomatic hips, with a high prevalence of bilateral deformities. In a subgroup of seventy patients with femoroacetabular impingement deformities, contralateral radiographic disease progression or the need for total hip arthroplasty was observed in 73% of hips. CONCLUSIONS: Osteoarthritis and osteonecrosis are the major causes of premature hip-joint failure in young patients. Femoroacetabular impingement abnormalities are usually bilateral and are commonly associated with progression of the disease to the contralateral hip.

The effect of the femoral head ossific nucleus in the treatment of developmental dysplasia of the hip. A meta-analysis.

BACKGROUND: The role of the presence of the femoral head ossific nucleus as a risk factor for the development of osteonecrosis of the femoral head in infants with developmental dysplasia of the hip has been investigated in several small studies, but the results have been inconsistent. The purpose of the present study was to determine the effect of the presence of the ossific nucleus on the development of osteonecrosis. METHODS: A systematic review of the medical literature from 1966 to 2007 was performed. Two independent reviewers evaluated all articles. Interrater agreement was determined, and the quality of evidence was evaluated. A meta-analysis was then performed with the main outcome defined as the development of osteonecrosis of the femoral head two years after reduction. RESULTS: Six observational studies (five retrospective and one prospective) met the inclusion criteria. Inconsistency was found in that half of the studies demonstrated a protective effect of the ossific nucleus on the development of osteonecrosis whereas half of the studies did not. A meta-analysis (including 358 patients) showed no significant effect of the presence of the ossific nucleus on the development of grades-I through IV osteonecrosis, with forty-one cases of osteonecrosis (19%) found in infants in whom the ossific nucleus had been present at the time of hip reduction compared with thirty cases (22%) in the group without an ossific nucleus (relative risk=0.75, 95% confidence interval=0.46 to 1.21). When only radiographic changes of grade II or worse were considered to represent osteonecrosis, a significant difference in the prevalence of osteonecrosis was found, with fourteen cases of osteonecrosis (7%) in infants with an ossific nucleus compared with eighteen cases (16%) in those without an ossific nucleus (relative risk=0.43, 95% confidence interval=0.20 to 0.90). A subgroup analysis showed that the presence of the ossific nucleus reduced the probability of osteonecrosis by 60% (relative risk=0.41, 95% confidence interval=0.18 to 0.91) after closed reduction, but no significant effect was found in patients treated with open reduction (relative risk=1.14, 95% confidence interval=0.62 to 2.07). All studies demonstrated methodological weaknesses compromising the quality of evidence. CONCLUSIONS: We did not find that the presence of the ossific nucleus had a significant effect on the development of osteonecrosis of any grade after hip reduction in infants with developmental dysplasia of the hip. The meta-analysis suggested that the presence of the ossific nucleus has a protective effect against the development of the more severe forms of femoral head osteonecrosis. However, the quality of evidence is moderate, and additional research is likely to have an important impact on the confidence in the estimate of the effect and may change this estimate.

Riparian plant species loss alters trophic dynamics in detritus-based stream ecosystems.

Riparian vegetation is closely connected to stream food webs through input of leaf detritus as a primary energy supply, and therefore, any alteration of plant diversity may influence aquatic ecosystem functioning. We measured leaf litter breakdown rate and associated biological parameters in mesh bags in eight headwater streams bordered either with mixed deciduous forest or with beech forest. The variety of leaf litter types in mixed forest results in higher food quality for large-particle invertebrate detritivores ('shredders') than in beech forest, which is dominated by a single leaf species of low quality. Breakdown rate of low quality (oak) leaf litter in coarse mesh bags was lower in beech forest streams than in mixed forest streams, a consequence of lower shredder biomass. In contrast, high quality (alder) leaf litter broke down at similar rates in both stream categories as a result of similar shredder biomass in coarse mesh bags. Microbial breakdown rate of oak and alder leaves, determined in fine mesh bags, did not differ between the stream categories. We found however aquatic hyphomycete species richness on leaf litter to positively co-vary with riparian plant species richness. Fungal species richness may enhance leaf litter breakdown rate through positive effects on resource quality for shredders. A feeding experiment established a positive relationship between fungal species richness per se and leaf litter consumption rate by an amphipod shredder (Gammarus fossarum). Our results show therefore that plant species richness may indirectly govern ecosystem functioning through complex trophic interactions. Integrating microbial diversity and trophic dynamics would considerably improve the prediction of the consequences of species loss.

DNA assays for detection, identification, and individualization of select agent microorganisms.

The purpose of this article is to review the status of DNA assays used for the detection, identification, and individualization of Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, and Brucella abortus. These select agent microorganisms are historically significant as they have either been used or experimented with as a bioweapon or as a terrorist agent and are the subject of intense research in the areas of biodefense and bioforensics. If the presence of a biological agent is suspected, sensitive and specific assays for rapid detection and identification are necessary. However, DNA methods for identification of the sample may also be applied in order to individualize the strain and potentially determine the source of the microorganism. Methods used at the Armed Forces Institute of Pathology (AFIP) for select agent microbial DNA analyses include DNA extraction, DNA quantitation, real-time polymerase chain reaction (real-time PCR) of genetic targets unique to the select agent microorganism, microbial 16S ribosomal RNA gene DNA sequencing, amplified fragment length polymorphism polymerase chain reaction (AFLP-PCR), and more recently, repetitive element polymerase chain reaction (REP-PCR) DNA fingerprinting. The methodologies of 16S ribosomal RNA gene DNA sequencing and DNA fingerprinting of microorganisms are well established within the field of diagnostic microbiology for DNA identification purposes, as well as DNA typing for epidemiological and genetic relatedness studies. 16S ribosomal RNA gene DNA sequencing and AFLP DNA fingerprinting have been validated at the Armed Force Institute of Pathology (AFIP) laboratory for identification purposes and can be used as a possible strain typing tool for Bacillus anthracis, Yersinia pestis, Francisella tularensis, as well as Brucella and Burkholderia species. The continued development and implementation of new DNA based methods with increased sensitivity and defined specificity will be particularly useful for the detection of residual microbial DNA signature in situations where the microorganism has been rendered nonviable by decontamination procedures or not able to be cultured on microbiological media.