Integrative taxonomy of Serrasentis gibsoni n. sp. (Acanthocephala: Isthmosacanthidae) from flatfishes in the Gulf of Mexico.

The Isthmosacanthidae acanthocephalan species of the genus Serrasentis are parasites of marine teleosts and an elasmobranch. In this study, Serrasentis gibsoni n. sp. is described from the intestines of four flatfish species (Paralichthyidae), namely Ancyclopsetta quadrocellata, Cyclopsetta chittendeni, Syacium gunteri, and S. papillosum from 10 oceanic sites in the Gulf of Mexico (GoM). Twenty sequences of the 'barcoding' region of cytochrome C oxidase subunit I gene were obtained from 20 adults of Serrasentis gibsoni n. sp. Additionally, five sequences of the barcoding region were obtained from five adults of rhadinorhynchid Gorgorhynchus lepidus from C. chittendeni, S. papillosum and one species of Haemulidae, Haemulom aurolineatum, from five oceanic sites from the GoM. Two phylogenetic approaches were followed: Bayesian inference and maximum likelihood. In both phylogenetic reconstructions, the sequences of Serrasentis gibsoni n. sp. were recovered as a monophyletic group within the genus Serrasentis and placed as a sister group to G. lepidus. However, due to the lack of molecular data for species of the Isthmosacanthidae and Rhadinorhynchidea, these phylogenetic inferences must be taken with caution. Serrasentis gibsoni n. sp. is the first species of Serrasentis described from Paralichthyidae flatfish species from marine waters of the Americas and from the GoM. Based on the barcoding data set analyzed, Serrasentis gibsoni n. sp. appears to have high intraspecific genetic variation; thus, it is necessary to continue exploring the genetic diversity of this species to infer its intraspecific evolutionary patterns.

Stephanostomum minankisi n. sp. (Digenea: Acanthocolpidae) from dusky flounder Syacium papillosum (Paralichthydae) from southern Gulf of Mexico: A new species without spines?

A new species of the genus Stephanostomum is described for the southeastern Gulf of Mexico based on morphological and nucleotide evidence. Stephanostomum minankisi n. sp. infects the intestine of the dusky flounder Syacium papillosum in the Yucatan Continental Shelf, Mexico (Yucatan Peninsula). Sequences of the 28S ribosomal gene were obtained and compared with available sequences of the other species and genera of the families Acanthocolpidae and Brachycladiidae from GenBank. A phylogenetic analysis was conducted, including 39 sequences, 26 of which represented 21 species and six genera of the family Acanthocolpidae. The new species is characterized by the absence of circumoral spines and spines on the tegument. Nonetheless, scanning electron microscopy consistently revealed the pits of 52 circumoral spines distributed in a double row with 26 spines each, and forebody spined. Other distinctive features of this species are testes in contact (sometimes overlapping), the vitellaria running along the body lateral fields to the mid-level of the cirrus-sac, pars prostatica and ejaculatory duct similar in length, and uroproct present. The phylogenetic tree showed that the three species found as parasites of dusky flounder (the new adult species and two in metacercaria stages) were grouped into two different clades. S. minankisi n. sp. was the sister species of Stephanostomum sp. 1 (Bt = 56) and formed a clade with S. tantabiddii, supported by high bootstrap values (100).

Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

Endoscopic ultrasound in the management of acute cholecystitis.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is increasingly utilised for patients with acute cholecystitis who are high-risk candidates for surgery. The technique to perform EUS-GBD has evolved and matured over the last two decades since EUS-GBD was first described in 2007 using a nasobiliary catheter. Compared to percutaneous gallbladder drainage (PT-GBD), EUS-GBD offers benefits of shorter hospitalisation stay and lesser procedural pain and need for reintervention. The purpose of this review is to provide an updated review of the equipment and techniques available for EUS-GBD, outcomes of the procedure and how it compares against endoscopic transpapillary drainage (ET-GBD), PT-GBD and laparoscopic cholecystectomy. Controversies surrounding the procedure will also be discussed.

The Norwich Osteoarthritis of the Ankle MRI Score (NOAMS): a reliability study.

AIM: To define and test the inter- and intra-rater reliability of a grading system for staging osteoarthritis (OA) of the ankle with magnetic resonance imaging (MRI) (Norwich Osteoarthritis of the Ankle MRI Score, NOAMS). MATERIALS AND METHODS: The MRI features to be included in the score were defined by a multidisciplinary expert panel through a Delphi process. An anonymised randomised dataset of 50 MRI studies was created from patients with concurrent plain radiographs to include 10 ankles of each of the Kellgren-Lawrence grades 0 to 4. Two experienced musculoskeletal radiologists and two trainees scored each ankle MRI twice independently and blinded to the plain radiographs. RESULTS: The inter-rater kappa coefficient of agreement for cartilage disease was 0.88 (95% confidence interval [CI]: 0.85, 0.91) for experienced raters and 0.71 (95% CI: 0.67, 0.76) for trainees. Inter-rater agreement for subchondral bone marrow oedema and cysts varied from 0.73 to 0.82 for experienced raters and from 0.63 to 0.75 for trainees with lowest 95% CI of 0.48 and 0.63. When bone marrow lesions were combined into a total joint score the level of agreement increased to between 0.88 and 0.97 with lowest 95% CI of 0.86. Combining cartilage zone scores did not increase the reliability coefficients. CONCLUSION: An expert panel considered that cartilage degradation and subchondral bone marrow lesions were the most important features for staging the severity of ankle OA on MRI. Experienced observers can grade the severity of ankle OA on MRI with a clinically useful high degree of reproducibility.

Discovery of a New Genus and Species of Allocreadiidae (Trematoda) in Mexico: Mesoamericatrema Magnisacculus n. Gen. n. Sp.

The trematodes of Allocreadiidae are mainly parasites of freshwater fish and the family contains 18 valid genera. Since 2004, 4 genera have been described in the Americas: Paracreptotrema, Paracreptotrematoides, Pseudoparacreptotrema and Auriculostoma, of which the latter was recently synonymized with Creptotrema by Franceschini et al., (2021). During a study in 2018 on fish parasites of Lacantún River, Chiapas, Mexico, allocreadiids were collected from the intestine of Atherinella alvarezi and morphological differences with other genera of the family were immediately noted. These differences were corroborated with molecular data and phylogenetic analyses, which indicated that it was a new genus and species. The objective of this study is to describe the new taxon, which we name Mesoamericatrema magnisacculus n. gen., n. sp. as well as to clarify its phylogenetic relationships, host specificity, and geographical distribution. For this, we carried out a meticulous study of the morphology and compared the new taxon with its congeners. We also obtained sequences of the 28S and ITS from the ribosomal RNA region that were used in generating molecular phylogenies and in calculating genetic distances with sequences of other species of Allocreadiidae available in the Genbank. The new genus is mainly characterized by having a very large cirrus sac in relation to the length of its body and nests in a clade that groups Creptotrema, Creptotrematina, Paracreptotrema, Paracreptotrematoides, Pseudoparacreptotrema and Wallinia, all of which have a Neotropical affinity in terms of their geographic and host distribution. Mesoamericatrema n. gen. is the fifth genus of Allocreadiidae to be described in the Americas since 2004, the third discovered in Mexico since 2016, and the first to be described as parasitizing Atheriniformes, which indicates that Middle America is a region where important speciation events have occurred in freshwater fish parasites.

Novel strain-level resolution of Crohn's disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing.

The mucosa-associated microbiota is widely recognized as a potential trigger for Crohn's disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn's disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn's disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.

Navigating systemic therapy for metastatic castration-naïve prostate cancer.

INTRODUCTION: The last decade has seen a remarkable shift in the treatment landscape of advanced prostate cancer, none more so than in the management of metastatic castration-naïve disease. METHODS: This narrative review will examine existing and emerging evidence supporting systemic therapy use for metastatic castration-naïve prostate cancer (mCNPC) and provide guidance on the selection of these agents with respect to optimising patient outcomes. RESULTS: The addition of either docetaxel (chemohormonal approach) or an AR pathway inhibitor (abiraterone, enzalutamide or apalutamide) is a reasonable standard of care option for men commencing long-term ADT for mCNPC. While the issue of disease volume as a predictive biomarker for docetaxel benefit has previously been debated, recent data support consideration of upfront docetaxel in all patients, regardless of metastatic burden. Decisions regarding systemic treatment for men with mCNPC should be based on comprehensive consideration of disease, patient and logistical factors. Multiple novel therapeutics for mCNPC are currently under active investigation. CONCLUSION: The introduction of potent systemic therapy earlier in the mCNPC disease course has resulted in dramatic improvements in clinical outcomes for patients. As the management of mCNPC continues to evolve, the future remains promising, with the expectation of ongoing improvements to patient outcomes and quality of life.

Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

Since the publication of this paper, the authors noticed an error in Fig. 1. The X-axis on all the figure panels should read 'Time (years)', not 'Time (months)'. The corrected Fig. 1 is shown below.

Delayed presentation of grade-IV renal injury post blunt trauma.

High-grade renal injuries are relatively uncommon in blunt trauma. They typically occur in the context of multisystem injuries. When present, these renal injuries are usually identified at the time of hospital presentation. Here, we present a case of delayed presentation of American Association for the Surgery of Trauma (AAST) grade-IV renal injury in a 61-year-old female who sustained multisystem injuries during a high-speed motor vehicle accident. To our knowledge, this is the first report case of delayed presentation of grade-IV renal injury. This case highlights the importance of serial examination and repeated imaging in complex trauma patients.

Negative magnetic resonance imaging in three cases of anterior tibial cortex stress fractures.

Anterior mid-tibial cortex stress fractures (ATCSF) are uncommon and notoriously challenging to treat. They are termed high risk due to their predilection to prolonged recovery, nonunion and complete fracture. Early diagnosis is essential to avoid progression and reduce fracture complications. Imaging plays a key role in confirming the diagnosis. Magnetic resonance imaging (MRI) is accepted as the gold standard modality due to its high accuracy and nonionizing properties. This report describes three cases of ATCSFs in recreational athletes who had positive radiographic findings with no significant MRI changes. Two athletes had multiple striations within their tibias. Despite the radiographic findings, their severity of symptoms were low with mild or no tenderness on examination. Clinicians should be mindful that the ATCSFs may not present with typical acute stress fracture symptoms. We recommend that plain radiographs should be used as the first line investigation when suspecting ATCSFs. Clinicians should be aware that despite MRI being considered the gold standard imaging modality, we report three cases where the MRI was unremarkable, whilst radiographs and computed tomography confirmed the diagnosis. We urge clinicians to continue to use radiographs as the first line imaging modality for ATCSFs and not to directly rely on MRI. Those who opt directly for MRI may be falsely reassured causing a delay in diagnosis.

Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

BACKGROUND: An increasing number and proportion of cancer patients with apparently localised disease are treated with chemotherapy and radiation therapy in contemporary oncology practice. In a pilot study of radiation-induced sarcoma (RIS) patients, we demonstrated that chemotherapy was associated with a reduced time to development of RIS. We now present a multi-centre collaborative study to validate this association. METHODS: This was a retrospective cohort study of RIS cases across five large international sarcoma centres between 1 January 2000 to 31 December 2014. The primary endpoint was time to development of RIS. RESULTS: We identified 419 patients with RIS. Chemotherapy for the first malignancy was associated with a shorter time to RIS development (HR 1.37; 95% CI: 1.08-1.72; P=0.009). In the multi-variable model, older age (HR 2.11; 95% CI 1.83-2.43; P<0.001) and chemotherapy for the first malignancy (HR 1.61; 95% CI 1.26-2.05; P<0·001) were independently associated with a shorter time to RIS. Anthracyclines and alkylating agents significantly contribute to the effect. CONCLUSIONS: This study confirms an association between chemotherapy given for the first malignancy and a shorter time to development of RIS.

Intraosseous hibernoma: a rare adipocytic bone tumour.

Hibernoma is a benign adipose tumour that contains foetal brown fat cells. We report a case of hibernoma arising in the left ischium of a 65-year-old female with a past history of ovarian carcinoma. The patient presented with a relatively short history of left sacral/hip pain. Radiologically, the lesion, which was large (5 cm) and sclerotic, had been stable for a number of years. Histologically, it was composed mainly of plump cells with foamy, multivacuolated cytoplasm. These cells showed no reaction for epithelial, melanoma or leucocyte markers but expressed FABP4/aP2 and S100, indicating that they were brown fat cells. There was no mitotic activity or nuclear pleomorphism and the lesion was diagnosed as a benign intraosseous hibernoma (IOH). IOH is a recently identified benign adipocytic lesion that presents typically as a sclerotic bone lesion. It has characteristic morphological and immunophenotypic features and should be regarded as a discrete primary bone tumour that needs to be distinguished from metastatic carcinoma/melanoma, chondrosarcoma and metabolic storage diseases containing numerous foamy macrophages.

The popliteal fibular ligament in acute knee trauma: patterns of injury on MR imaging.

OBJECTIVE: To describe the patterns of injury associated with injury to the popliteofibular ligament injury. MATERIALS AND METHODS: A retrospective review was performed of 180 MRI scans undertaken for acute knee trauma. Scans were excluded if the time of injury was over 4 weeks from the time of the scan, or if there was a history of septic arthritis, inflammatory arthropathy, previous knee surgery, or significant artefact. An agreed criterion for assessing the structures of the posterolateral ligamentous complex was defined and in each scan, the popliteofibular ligament (PFL) was scored as normal or injured. The menisci, ligaments, and tendons of each knee were also assessed. RESULTS: The mean age was 25.7 years (range, 9-65 years) and 72.2% (n = 130) patients were male. The PFL was injured in 36 cases (20%). There is a significant association between PFL injury and ACL rupture (p = 0.0001), ITB injury (p = 0.0001), PCL injury (p = 0.0373), in addition to associations with injury to other posterolateral corner structures including the lateral collateral ligament (p = 0.0001), biceps femoris tendon (p = 0.0014), and popliteus tendon (p = 0.0014). Of our series of PFL injuries, nine cases (25%) were associated with further injuries of posterolateral corner structures and in 27 cases (75%) the PFL was the only posterolateral corner structure torn. CONCLUSIONS: PFL injury is not uncommon in acute knee trauma and is associated with significant internal derangement of the knee, especially anterior cruciate ligament rupture, ITB sprain, and injury to other structures within the posterolateral corner.

Isoprenylcysteine carboxylmethyltransferase regulates mitochondrial respiration and cancer cell metabolism.

Isoprenylcysteine carboxylmethyltransferase (Icmt) catalyzes the last of the three-step posttranslational protein prenylation process for the so-called CaaX proteins, which includes many signaling proteins, such as most small GTPases. Despite extensive studies on Icmt and its regulation of cell functions, the mechanisms of much of the impact of Icmt on cellular functions remain unclear. Our recent studies demonstrated that suppression of Icmt results in induction of autophagy, inhibition of cell growth and inhibition of proliferation in various cancer cell types, prompting this investigation of potential metabolic regulation by Icmt. We report here the findings that Icmt inhibition reduces the function of mitochondrial oxidative phosphorylation in multiple cancer cell lines. In-depth oximetry analysis demonstrated that functions of mitochondrial complex I, II and III are subject to Icmt regulation. Consistently, Icmt inhibition decreased cellular ATP and depleted critical tricarboxylic acid cycle metabolites, leading to suppression of cell anabolism and growth, and marked autophagy. Several different approaches demonstrated that the impact of Icmt inhibition on cell proliferation and viability was largely mediated by its effect on mitochondrial respiration. This previously unappreciated function of Icmt, which can be therapeutically exploited, likely has a significant role in the impact of Icmt on tumorigenic processes.

Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies.

The probability of survival is conventionally calculated from autologous hematopoietic cell transplantation (aHCT). Conditional survival takes into account the changing probability of survival with time survived, but this is not known for aHCT populations. We determined disease- and cause-specific conditional survival for 2388 patients treated with aHCT over a period of 20 years at a single institution. A total of 1054 deaths (44% of the cohort) were observed: 78% attributed to recurrent disease; 9% to subsequent malignancies and 6% to cardiopulmonary disease. Estimated probability of relative survival was 62% at 5 years and 50% at 10 years from aHCT. On the other hand, the 5-year relative survival was 70, 75, 81 and 88% after having survived 1, 2, 5 and 10 years after aHCT, respectively. The cohort was at a 13.9-fold increased risk of death compared with the general population (95% confidence interval (CI)=13.1-14.8). The risk of death approached that of the general population for 10-year survivors (standardized mortality ratio (SMR)=1.4, 95% CI=0.9-1.9), with the exception of female Hodgkin's lymphoma patients transplanted before 1995 at age 40 years (SMR=6.0, 95% CI=1.9-14.0). Among those who had survived 10 years, nonrelapse-related mortality rates exceeded relapse-related mortality rates. This study provides clinically relevant survival estimates after aHCT, and helps inform interventional strategies.

Idiopathic hypercalcemia in infants with renal dysplasia.

BACKGROUND: We have observed infants with renal dysplasia who developed sustained hypercalcemia, without vitamin D or calcium supplementation (idiopathic). This has not been previously described. OBJECTIVES: 1) Define incidence, severity and duration of idiopathic hypercalcemia in infants with renal dysplasia below 12 months of age. 2) Evaluate phosphate, parathyroid hormone (PTH) and vitamin D levels in these infants. METHODS: A retrospective study was conducted from June 2005 to June 2008. Patients receiving calcium-containing phosphate binders or daily supplemental vitamin D in excess of 400 IU were excluded. Hypercalcemia was defined as at least three corrected calcium values above normal lab values for age, in a one-week interval. RESULTS: 15 of 99 (15%) infants with renal dysplasia had hypercalcemia. All were males; 10/15 (67%) were below one month of age at presentation; 9/15 (60%) had posterior urethral valves (PUV). Mean hypercalcemia duration was 5.2 ± 6.0 months. Mean corrected calcium was 3.07 mmol/l (12.3 mg/dl). Only 3/10 infants had elevated PTH levels. None had elevated phosphate levels and only 1/8 patients who had 25-hydroxyvitamin D measured had an elevated level. CONCLUSIONS: Idiopathic hypercalcemia in infants with renal dysplasia is common. Neonates and those with PUVs are at greatest risk. Most have normal levels of 25-hydroxyvitamin D, phosphate and PTH.