Anaesthesia-related morbidity associated with recumbent, low-field magnetic resonance imaging of horses.

CASE HISTORY: Medical records from 2009 to 2021 from a private equine referral hospital in Rochester, NH, USA were analysed for cases that underwent general anaesthesia for low-field MRI of the distal limb. These were used to determine peri-anaesthetic morbidity and mortality. CLINICAL FINDINGS AND OUTCOME: Two hundred and forty-three anaesthetic episodes were recorded in horses undergoing low-field MRI. The peri-anaesthetic complication rate prior to discharge was 6.2% (15/243). No patients experienced a fatal complication. Ninety two of the 243 patients had multiple sites imaged, 90/243 received pre-anaesthetic dantrolene, 134/243 received intra-anaesthetic dobutamine, and 15/243 were positioned in dorsal recumbency. Complications included: abdominal discomfort ("colic"; 9/243), myopathy (4/243), hyphaema (1/243) and carpal fracture (1/243). At the time of discharge, 14/15 complications had resolved. Of 135 horses for which data were available 55 became hypotensive during the procedure (lowest mean arterial pressure < 65 mmHg). Median body weight was 553 (min 363, max 771) kg. Horses were anaesthetised for a median of 150 (min 45, max 210) minutes. There was no evidence of an association between higher body weight (p = 0.051) or longer duration of anaesthesia (p = 0.421) and development of an anaesthetic complication. For categorical variables (dantrolene administration pre-anaesthesia, dobutamine administration during anaesthesia, hypotension (mean < 65 mmHg) during anaesthesia, dorsal vs. lateral recumbency, and imaging of single vs. multiple sites), the 95% CI for the OR included 1, indicating a lack of effect of the variable on the odds of complication. CLINICAL RELEVANCE: The cases included in this series suggest that low-field MRI under general anaesthesia is a viable option for diagnostic imaging in otherwise healthy horses. Complications occur, but most resolve before discharge.

Pregabalin reduces opioid consumption and hyperalgesia but not pain intensity after laparoscopic donor nephrectomy.

BACKGROUND: Gabapentinoids are increasingly used to reduce acute postoperative pain, opioid consumption and opioid-related adverse effects. We explored the opioid-sparing, analgesic and anti-hyperalgesic effect of perioperative administered pregabalin in laparoscopic living donor nephrectomy. METHODS: In this randomized controlled trial, 80 patients were recruited and randomized to receive pregabalin 150 mg twice daily or placebo on the day of surgery and the first postoperative day as part of a multimodal analgesic regimen. Primary outcome was opioid consumption 0-48 h after surgery. Secondary outcomes were pain intensity at rest and with movement 0-48 h after surgery using the 0-10 Numeric Rating Scale and incisional hyperalgesia measured 24 h post-surgery and at hospital discharge. Further secondary outcomes were adverse effects. Persistent post-surgical pain was registered 6 weeks, 6 and 12 months after surgery. RESULTS: Pregabalin significantly reduced opioid consumption compared with placebo 0-48 h after surgery (median mg [25th, 75th percentile]); 29.0 (22.0-45.5) vs. 41.8 (25.8-63.6) (P = 0.04). Pain intensity 0-48 h after surgery calculated as area under the pain (NRS) vs. time curve was not statistically different between groups at rest (P = 0.12) or with movement (P = 0.21). Pregabalin decreased incisional hyperalgesia 24 h after surgery (median cm [25th, 75th percentile] 8.5 (1.0-18.5) vs. 15.5 (9.5-24.0) (P = 0.02). Nausea (P ≤ 0.01), use of antiemetics (P ≤ 0.01) and pain-related sleep interference (P = 0.02) were reduced with pregabalin. CONCLUSIONS: Perioperative pregabalin added to a multimodal analgesic regimen was opioid-sparing, but made no difference to pain intensity score 0-48 h after surgery. Pregabalin may reduce incisional hyperalgesia on the first day after surgery.

Inclusion of an IgG1-Fc spacer abrogates efficacy of CD19 CAR T cells in a xenograft mouse model.

Cancer therapy with T cells expressing chimeric antigen receptors (CARs) has produced remarkable clinical responses in recent trials, but also severe side effects. Whereas most protocols use permanently reprogrammed T cells, we have developed a platform for transient CAR expression by mRNA electroporation. This approach may be useful for safe clinical testing of novel receptors, or when a temporary treatment period is desirable. Herein, we investigated therapy with transiently redirected T cells in vitro and in a xenograft mouse model. We constructed a series of CD19-specific CARs with different spacers and co-stimulatory domains (CD28, OX40 or CD28-OX40). The CAR constructs all conferred T cells with potent CD19-specific activity in vitro. Unexpectedly, the constructs incorporating a commonly used IgG1-CH2CH3 spacer showed lack of anti-leukemia activity in vivo and induced severe, partly CD19-independent toxicity. By contrast, identical CAR constructs without the CH2-domain eradicated leukemia in vivo, without notable toxicity. Follow-up studies demonstrated that the CH2CH3-spacer bound soluble mouse Fcγ-receptor I and mediated off-target T-cell activation towards murine macrophages. Our findings highlight the importance of non-signalling CAR elements and of in vivo studies. Finally, the results show that transiently redirected T cells control leukemia in mice and support the rationale for developing an mRNA-CAR platform.

Retinal ependymoma: an immunohistologic and ultrastructural study.

Glial tumors of the retina are rare. Most are syndrome associated and include pilocytic astrocytoma in neurofibromatosis type 1 and subependymal giant cell astrocytoma in tuberous sclerosis complex. Acquired, more conventional, diffuse astrocytomas are less frequent. Ependymoma is exquisitely rare. Herein, we report the clinicopathologic features of the second case of retinal ependymoma. The tumor was sporadic in occurrence and unilateral, low grade, and of cellular type. Its chronic course and large size prompted an initial pathologic diagnosis of "massive retinal gliosis." The literature regarding retinal glial neoplasia including ependymoma as well as the so-called massive retinal gliosis is discussed.

Traumatic head injury in infants and toddlers.

AIM: To describe the presenting characteristics, type of injury and hospital course in young children with traumatic head injury, and to identify characteristics indicating that the trauma was inflicted. METHODS: A retrospective medical record review of 91 children less than 3 years of age who were admitted to a tertiary teaching hospital in Norway from 1995 through 2005 with a traumatic head injury. Patients were identified by diagnostic codes, and categorized by type of injury as skull fractures (n = 39), epidural haemorrhage (EDH) (n = 12), subdural haemorrhage (n = 27) and parenchymal brain injury (n = 13). Further the cases were classified as inflicted injury (n = 17), accident (n = 35) or indeterminate (n = 39). RESULTS: The mechanism of injury was similar for EDHs and isolated skull fractures, and none were classified as inflicted. Sixty-three percent of the cases with subdural haematoma were classified as inflicted. When compared to the accident group, children in the inflicted group more frequently had subdural haemorrhage without a skull fracture (OR = 6.9, CI = 1.7-28.2), and seizures (OR = 9.5, CI = 2.1-43.3). CONCLUSIONS: Inflicted and accidental head injuries differed in presenting characteristics and injury type. Nearly two-third of the subdural haemorrhages were classified as inflicted, but none of the epidural EDHs or skull fractures. Inflicted injuries tended to present with seizures.

Typeability of Tn1546-like elements in vancomycin-resistant enterococci using long-range PCRs and specific analysis of polymorphic regions.

Molecular subtyping of the VanA-type resistance element Tn1546 in an international collection of 81 genomically diverse vancomycin-resistant enterococci (VRE) from human, animal, and environmental reservoirs was evaluated by restriction analysis of long-range PCR amplicons (PCR-RFLP), single gene PCRs, Southern blot analysis of genomic digests, and partial DNA sequencing. A dominant Tn1546-RFLP in accordance with Enterococcus faecium BM4147 was detected in 43 of the 49 long-range PCR positive strains from ecologically diverse sources in several European countries and the US. Tn1546-like elements from the 32 (40%) long-range PCR negative strains were typed into 17 different groups by single-gene PCRs and Southern blot analysis of the ORF1, ORF2, vanS-vanH, vanX-vanY, and vanZ regions. All these isolates showed deletions in the ORF1 and/or vanZ primer binding regions explaining the failure of long-range PCR amplification. Enlarged vanS-vanH or vanX-vanY fragments were detected in 7 (22%) and 16 (50%) of the long-range PCR negative strains, respectively. The enlarged vanS-vanH regions of five clinical isolates from the US (n = 2), Ireland (n = 2), and Norway (n = 1) contained identical IS1251-like insertions indicating intercontinental spread of the vanA gene cluster. Intergenic vanS-vanH IS1251 insertions have so far not been reported in European studies. Structural rearrangements of Tn1546-like elements may represent single recombination events that can serve as fingerprints in the molecular examination of vanA gene cluster evolution and transmission. The optimal strategy for such analysis has yet to be determined. Two alternative long-range PCRs with subsequent RFLP analysis were successfully used to type the majority of vanA gene clusters in an ecologically and geographically heterogeneous VRE strain collection, but failed to detect and type a group of variant Tn1546-like elements truncated in the left-end ORF1/ORF2 region. Further subtyping of such variants should specifically target the polymorphic vanS-vanH and vanX-vanY regions.

Herbal remedies, nephropathies, and renal disease.

The use of herbal remedies is becoming increasingly popular in the United States. Research has shown that herbal remedy use may be associated with acute renal failure. In addition, the use of herbal remedies may be detrimental for the patient with compromised renal function. Patients with renal insufficiency or renal failure may be at risk for further kidney damage as well as complications related to interactions of herbal remedies with complex renal therapy regimens. This article will describe the escalating use of herbal therapy and the hazards of herbal remedy use among patients.

Clear cell mesothelioma.

A clear cell form of epithelial mesothelioma is described. This variant does not appear to have been previously described, and it merits recognition since it is readily confused by routine light microscopy with other tumors that involve the pleura, including metastatic carcinomas composed predominantly of cells with optically clear cytoplasm. Ultrastructural and immunohistochemical studies were helpful in reaching the diagnosis in this case, and electron microscopy is particularly recommended to investigate the differential diagnosis of unusual pleural tumors.

Moving beyond the Patient Self-Determination Act: educating patients to be autonomous.

This article explores the limitations of the Patient Self-Determination Act. We need to think of advance directives as a process of understanding, reflecting, and discussing, not just a written document. Further, health care professionals must initiate the process of advance directive education in the outpatient setting. Our dialysis unit has successfully integrated this view into daily care of patients and families.

Spindling artifact of urothelial cells in post-laser treatment urinary cytology.

We reviewed 22 post-laser (Nd:YAG laser) coagulation bladder washes collected immediately after treatment. All washes demonstrated a striking artifact of cellular spindling. These spindled cells occurred singly, in loose clusters, and in lamellar stacks and had elongated nuclei with dense chromatin and bipolar cytoplasm that was fused in the stacks. Concurrent biopsies demonstrated similar cytologic changes. The spindling is a nonspecific epithelial response to heat. Conventionally electrocauterized epithelia show this artifact in biopsies, but since only the base of the lesion and surrounding urothelium are subjected to heat with electrocautery, the relatively few spindled epithelial cells created presumably go undetected in cytology specimens. With laser treatment, however, the whole urothelial surface of the lesion is coagulated, producing a much greater number of spindled cells. It is important to avoid misinterpreting the spindled cells as cells from a mesenchymal neoplasm or a sarcomatoid carcinoma, mistakes that were made in some of our initial cases. Malignancy cannot be evaluated when cells exhibit spindling artifact; this judgement should be made on undistorted cells. Thus, pre-laser and post-laser washes should be submitted for evaluation of malignancy.

Plasmacytoid transitional cell carcinoma. Report of a case with initial presentation mimicking multiple myeloma.

The case of a 63-year-old man with a previously undescribed morphologic variant of transitional cell carcinoma of the urinary bladder is reported. The patient initially presented with multiple lytic bony metastases of the ribs and skull. Aspiration biopsy of one of the lytic lesions of the skull showed tumor cells with a striking plasmacytoid appearance, similar to the plasma cells seen in myeloma, leading to an initial observer's diagnosis of multiple myeloma. Subsequently, a bladder tumor with the same cytomorphology was found; immunohistochemical and ultra structural studies performed on the aspirated material and on the bladder biopsy specimen clearly established the epithelial nature of this neoplasm.

Nasopharyngeal angiofibroma treated in 1841 by maxillectomy.

One of the earliest recorded maxillectomy procedures was carried out on a 21-year-old male in University College Hospital, London, in 1841 by Mr. Liston. The case report and operative procedure are given. The gross, radiographic and microscopic features of the resection specimen, which was preserved until the present as a museum specimen, are provided. The tumor is an advanced nasopharyngeal angiofibroma and demonstrates the mode of spread of this lesion when treatment is delayed.

Primary B-cell gastric lymphoma--a reassessment of its histogenesis.

Primary gastric lymphoma, (PGL), is thought to be a tumour of follicle centre cell origin containing centrocyte-like (CCL) cells, and plasma cell components. The advent of novel leucocyte antibodies reactive in paraffin sections and improved techniques for the demonstration of immunoglobulin (Ig) in tissues has permitted a reassessment of the histogenesis of PGL. Our results have shown that PGL is a tumour of CCL cells with plasma cell differentiation in a minority of cases. Follicles were reactive, as defined by polytypic expression of Ig, in each case but selective invasion of reactive follicles by neoplastic CCL cells often led to a misleading appearance of malignancy. CCL cells bear close similarities to marginal zone cells which have been defined as a distinct non-circulating B-cell lineage. This could account for the favourable clinical behaviour of PGL.