Effect of conventional multilevel brachycephalic obstructive airway syndrome surgery on clinical and videofluoroscopic evidence of hiatal herniation and gastroesophageal reflux in dogs.

OBJECTIVE: To evaluate the effect of conventional multilevel surgery (CMS) for brachycephalic obstructive airway syndrome (BOAS) on associated sliding hiatal hernia (SHH) and/or gastroesophageal reflux (GER). STUDY DESIGN: Prospective clinical trial. ANIMALS: Sixteen client-owned dogs with clinical signs consistent with BOAS and associated SHH and GER. METHODS: All dogs were treated with 1 or more components of CMS including soft palate resection, laryngeal ventriculectomy, and alaplasty. A standardized Dog Swallowing Assessment Tool (Dog SAT) questionnaire was completed by owners preoperatively and postoperatively. Videofluoroscopic swallow studies (VFSS) were used to evaluate esophageal motility, gastroesophageal reflux, and hiatal herniation preoperatively, and in a subset of dogs postoperatively. Upper gastrointestinal endoscopic studies were performed to document esophagitis and lower esophageal sphincter pathology. RESULTS: All dogs were discharged from the hospital. One dog experienced aspiration pneumonia immediately postoperatively. Owner-assigned clinical scores improved in scores related to regurgitation after eating and regurgitation (P = .012) during increased activity/exercise (P = .002) between preoperative and postoperative time points. However, no improvement was detected in masked assessment of preoperative and postoperative VFSS studies in terms of GER frequency (P = .46) or severity (P = .79), SHH frequency (P = .082) or severity (P = .34) scores. CONCLUSION: Owners of dogs treated with CMS perceived an improvement in clinical signs of SHH and GER that was not confirmed by VFSS studies. CLINICAL SIGNIFICANCE: Conventional multilevel surgery in dogs with BOAS does not appear to consistently resolve SHH and GER, although clinical signs may improve.

Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS).

BACKGROUND: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. METHODS: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. RESULTS: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. CONCLUSIONS: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Daratumumab utilization and cost analysis among patients with multiple myeloma in a US community oncology setting.

Background: The introduction of daratumumab into the treatment of multiple myeloma has improved outcomes in patients; however, community oncologists often dose more frequently than the US FDA-approved label. Materials and methods: Integra analyzed its database to elucidate daratumumab treatment patterns and the impact of increased utilization on the cost of care for multiple myeloma. Results: Following week 24, 671 (65%) of 1037 patients remained on daratumumab-containing regimens, with 330 patients continuing more frequent treatments than the expected once-every-4-weeks dosing described in the standard dosing schedule. Patients received an average of 14% more daratumumab doses than the FDA-approved label indicates, increasing the 1-year daratumumab costs by an estimated US$31,353. Conclusion: Daratumumab is utilized more frequently than the FDA-recommended dosing, leading to higher multiple myeloma treatment costs.

Lay abstract Since its first approval in 2015, daratumumab has become the backbone of many multiple myeloma treatment regimens. While its approval has improved outcomes in many patients who undergo treatment, it is expensive and has largely contributed to the increasing costs of care in multiple myeloma. In its most common treatment schedule, patients should transition from weekly and biweekly dosing to treatment once every 4 weeks. However, many providers maintain their patients on a more frequent dosing schedule, which increases Medicare 1-year costs by an estimated US$31,353 and may have unforeseen impacts on adverse events and patient outcomes.

Real-world ibrutinib dose reductions, holds and discontinuations in chronic lymphocytic leukemia.

Aim: A retrospective chart review of ibrutinib-treated patients with chronic lymphocytic leukemia (CLL) was conducted. Patients & methods: Adults with CLL who initiated ibrutinib were followed for ≥6 months (n = 180). Results: Twenty-five percent of first-line ibrutinib patients experienced ≥1 dose reduction, mainly due to adverse events (AEs; 79%). Treatment discontinuations and dose holds occurred in 20 and 34% of patients, respectively, most commonly due to AEs (73 and 74%). Approximately one-quarter of relapsed/refractory ibrutinib patients experienced ≥1 dose reduction, mainly due to AEs (88%). Treatment discontinuation and dose holds occurred in 40% of patients (58 and 76% due to AEs, respectively). Conclusion: Dose reductions, holds and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice.

Lay abstract Chronic lymphocytic leukemia (CLL) is a cancer that develops from a type of white blood cells called 'B cells.' Ibrutinib is a targeted therapy that inhibits the activity of a protein called Bruton's tyrosine kinase, which plays a key role in CLL. Patients receiving ibrutinib treatment can experience side effects ('adverse events'). In addition, patients may need to reduce their drug dose ('dose reductions') or stop treatment ('discontinuations') for a variety of reasons. We reviewed patients' charts to describe dose reductions and discontinuations in ibrutinib-treated patients with CLL. Our results indicate that dose reductions and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice, and that the most common reason was adverse events.

Clinical and videofluoroscopic outcomes of laparoscopic treatment for sliding hiatal hernia and associated gastroesophageal reflux in brachycephalic dogs.

OBJECTIVE: To describe a laparoscopic technique for treatment of sliding hiatal hernia (SHH) and associated gastroesophageal reflux (GER) in brachycephalic dogs and document clinical and videofluoroscopic outcomes postoperatively. STUDY DESIGN: Prospective clinical trial. ANIMALS: Eighteen client-owned dogs. METHODS: A three-port laparoscopic approach was used. Intracorporeal suturing was used for hiatal plication and esophagopexy, and left-sided laparoscopic or laparoscopic-assisted gastropexy was performed. A standardized canine dysphagia assessment tool (CDAT) questionnaire was completed by owners pre- and postoperatively. Videofluoroscopic swallow studies (VFSS) were used to evaluate esophageal function, and impedance planimetry was used to assess lower esophageal sphincter geometry preoperatively and in a subset of dogs postoperatively. RESULTS: Median age was 27.5 (range 5-84) months. Conversion to open surgery was necessary in 1 (5.5%) of 18 dogs. Regurgitation after eating, and associated with activity/exercise, improved significantly when comparing pre- and postoperative CDAT assessments. Hiatal hernia and GER severity scores improved significantly between pre- and postoperative VFSS assessments, whereas SHH and GER frequency scores did not. One dog developed pneumothorax intraoperatively, underwent cardiopulmonary arrest, and died. Minor complications included splenic (n = 6) and hepatic lacerations (n = 3) that did not require specific therapy. CONCLUSION: A laparoscopic approach to treatment of SHH and GER led to improvements in clinical and VFSS indices in the majority of brachycephalic dogs. However, a subset of dogs still demonstrated some clinical signs postoperatively. CLINICAL RELEVANCE: In experienced hands, laparoscopic treatment of SHH and GER offers a minimally invasive alternative to open surgery.

Percutaneous radiologically guided gastrostomy tubes: Procedural description and biomechanical comparison in a canine model.

OBJECTIVE: To describe the novel placement of percutaneous radiologically guided gastrostomy (PRG) tubes in a canine cadaveric model and to biomechanically compare PRG and percutaneous endoscopic gastrostomy (PEG) tube constructs. STUDY DESIGN: Descriptive and biomechanical experimental study. ANIMALS: Fifteen large breed (>25 kg) canine cadavers. METHODS: Percutaneous endoscopic gastrostomy tubes, low-profile PRG tubes, and standard PRG tubes were each placed in five canine cadavers. Body wall and stomach (with attached gastrostomy tube constructs) were harvested and biomechanically tested. Data regarding the maximal load to failure and procedure time were statistically analyzed. RESULTS: Percutaneous endoscopic gastrostomy and PRG tube placement was successful in all cadavers with no procedure-related complications. Gastrostomy tube placement time was longer for the PEG group vs the low-profile PRG (P = .005) and standard PRG (P = .037) groups. Peak construct strength was lower for the PEG group vs the low-profile PRG (P = .002) and standard PRG (P = .010) groups. The site of failure varied among groups. CONCLUSION: Percutaneous radiologically guided gastrostomy tubes were successfully placed in all cases with shorter placement time and greater peak construct strength compared with PEG tubes. CLINICAL SIGNIFICANCE: Due to the increased load to failure as well as decreased placement time recorded for PRG tubes relative to PEG tubes, PRG tubes may be considered as an alternative minimally invasive gastrostomy option in large breed canine patients. Further evaluation in clinical animals is required. Results of this work were presented at the 2019 American College of Veterinary Surgeons Surgery Summit; October 16-19, 2019; Las Vegas, Nevada.

Implementation of surgical debriefing programs in large health systems: an exploratory qualitative analysis.

BACKGROUND: The role of the "debrief" to address issues related to patient safety and systematic flaws in care is frequently overlooked. In our study, we interview surgical leaders who have developed successful strategies of debriefing within a comprehensive program of quality improvement. METHODS: Semi-structured interviews of four implementation leaders were performed. The observations, beliefs and strategies of surgical leaders are compared and contrasted. Common themes are identified related to program success and failure. Quality and safety researchers performed, coded and categorized the interviews and coordinated the analysis and interpretation of the results. The authors from the four institutions aided in interpretation and framing of the results. RESULTS: The debriefing programs evaluated were part of comprehensive quality improvement projects. Seven high-level themes and 24 subthemes were identified from the interviews. Themes related to leadership included early engagement, visible ongoing commitment and enforcement. Success appeared to depend upon meaningful and early debriefing feedback. The culture of safety that promoted success included a commitment to open and fair communication and continuous improvement. There were many challenges to the success of debriefing programs. The loss of institutional commitment of resources and personnel was the instigating factor behind the collapse of the program at Michigan. Other areas of potential failure included communication issues and loss of early and meaningful feedback. CONCLUSIONS: Leaders of four surgical systems with strong debriefing programs report success using debriefing to improve system performance. These findings are consistent with previously published studies. Success requires commitment of resources, and leadership engagement. The greatest gains may be best achieved by programs that provide meaningful debriefing feedback in an atmosphere dedicated to open communication.

Prospective evaluation of outcome of dogs with intrahepatic portosystemic shunts treated via percutaneous transvenous coil embolization.

OBJECTIVE: To report outcome and complications after percutaneous transvenous coil embolization (PTCE) and evaluate the clinical, laboratory, and imaging changes in dogs with intrahepatic portosystemic shunts (IHPSS) pre-PTCE and post-PTCE. STUDY DESIGN: Prospective clinical trial. ANIMALS: Twenty-five dogs (15 dogs in imaging subgroup) with IHPSS. METHODS: Clinical signs, hematologic, and biochemical parameters were recorded before and 3 months after PTCE. All dogs received the same medical treatment and underwent PTCE. In the imaging subgroup, ultrasonography, hepatic portal scintigraphy, and computed tomography-angiography were performed pre-PTCE and post-PTCE. RESULTS: All evaluated bloodwork values improved by at least 50% of their initial value, by 3 months post-PTCE. Liver volume increased after PTCE (P = .001), but remained lower than normal in 11/15 dogs. Hepatic arterial fraction decreased after PTCE (P = .029), consistent with increased portal blood flow to the liver. Twenty-four of 25 dogs were available for reevaluation at 3 months, and all abnormal clinical signs had resolved in 22/24 dogs. CONCLUSION: PTCE appears promising as a treatment for IHPSS, as clinical signs resolved in most cases, bloodwork abnormalities often normalized, and the procedure was performed safely with minimal complications. PTCE increased hepatic portal perfusion and liver volume in most dogs. These promising results justify a future randomized clinical trial comparing PTCE, other attenuation options, and medical management alone.

The prevalence of dynamic pharyngeal collapse is high in brachycephalic dogs undergoing videofluoroscopy.

The aim of this retrospective study was to determine the frequency of pharyngeal collapse in a large group of brachycephalic dogs undergoing videofluoroscopic assessment of swallowing or airway diameter. We hypothesized that brachycephalic dogs would have pharyngeal collapse more frequently than dolichocephalic or mesocephalic dogs with or without airway collapse. The medical records database was searched for brachycephalic dogs undergoing videofluoroscopy of swallowing or airway diameter between January 1, 2006 and December 31, 2015. A cohort of dolichocephalic/mesocephalic dogs with videofluoroscopically confirmed airway collapse was age and time matched for comparison. A control group of dolichocephalic/mesocephalic dogs that did not have documented airway collapse was also evaluated. All fluoroscopic studies were assessed by a board certified veterinary radiologist for the presence and degree of pharyngeal collapse. Results demonstrate that pharyngeal collapse was significantly more common in brachycephalic dogs (58/82; 72%) than in nonbrachycephalic dogs with (7/25; 28%) and without (2/30; 7%) airway collapse. Pharyngeal collapse is more prevalent in brachycephalic dogs undergoing videofluoroscopy than in dolichocephalic/mesocephalic dogs with or without airway collapse.

The impact of the omission or inadequate dosing of radiotherapy in extranodal natural killer T-cell lymphoma, nasal type, in the United States.

BACKGROUND: Extranodal natural killer T-cell lymphoma, nasal-type (NKTCL), is a rare malignancy in Western populations and is thus challenging for standardization of care and a prospective study. This study was aimed at defining patterns of care for NKTCL in the context of radiotherapy (RT) use and dose selection in the United States. METHODS: Six hundred forty-two stage I-II NKTCL patients from 1998 to 2012 were identified from the National Cancer Data Base. Binary logistic regression analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of the treatment selection and RT dose. Overall survival (OS) analyses were completed with the Kaplan-Meier and Cox multivariate methods, including a propensity score adjustment for a potential indication bias. RESULTS: Of the 642 included NKTCL patients, 70% were at stage I, 79% were white, and 66% were ≤ 60 years old. Fifty-five percent received chemotherapy plus RT, 19% received RT alone, and 27% received chemotherapy alone. The median RT dose was 50 Gy (interquartile range, 43.2-54 Gy), 37% received < 45 Gy, and 43% received < 50 Gy. A multivariate survival analysis showed improved OS in comparison with chemotherapy alone for RT alone at ≥50 Gy (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.70; P < .01), for chemotherapy plus RT at <50 Gy (HR, 0.55, 95% CI, 0.36-0.86; P < .01), and for chemotherapy plus RT at ≥50 Gy (HR, 0.41; 95% CI, 0.27-0.63; P < .01). CONCLUSIONS: Stage I-II NKTCL patients in the United States commonly receive chemotherapy alone or suboptimal-dose RT. The omission of RT or the use of suboptimal RT is negatively associated with OS. Efforts to continue improving evidenced-based management are warranted. Cancer 2017;123:3176-85. © 2017 American Cancer Society.

Multilaboratory Survey To Evaluate Salmonella Prevalence in Diarrheic and Nondiarrheic Dogs and Cats in the United States between 2012 and 2014.

Eleven laboratories collaborated to determine the periodic prevalence of Salmonella in a population of dogs and cats in the United States visiting veterinary clinics. Fecal samples (2,965) solicited from 11 geographically dispersed veterinary testing laboratories were collected in 36 states between January 2012 and April 2014 and tested using a harmonized method. The overall study prevalence of Salmonella in cats (3 of 542) was <1%. The prevalence in dogs (60 of 2,422) was 2.5%. Diarrhea was present in only 55% of positive dogs; however, 3.8% of the all diarrheic dogs were positive, compared with 1.8% of the nondiarrheic dogs. Salmonella-positive dogs were significantly more likely to have consumed raw food (P = 0.01), to have consumed probiotics (P = 0.002), or to have been given antibiotics (P = 0.01). Rural dogs were also more likely to be Salmonella positive than urban (P = 0.002) or suburban (P = 0.001) dogs. In the 67 isolates, 27 unique serovars were identified, with three dogs having two serovars present. Antimicrobial susceptibility testing of 66 isolates revealed that only four of the isolates were resistant to one or more antibiotics. Additional characterization of the 66 isolates was done using pulsed-field gel electrophoresis and whole-genome sequencing (WGS). Sequence data compared well to resistance phenotypic data and were submitted to the National Center for Biotechnology Information (NCBI). This study suggests an overall decline in prevalence of Salmonella-positive dogs and cats over the last decades and identifies consumption of raw food as a major risk factor for Salmonella infection. Of note is that almost half of the Salmonella-positive animals were clinically nondiarrheic.

Prospective evaluation of surgical management of sliding hiatal hernia and gastroesophageal reflux in dogs.

OBJECTIVE: To evaluate response to surgical management of sliding hiatal hernia (SHH) and gastroesophageal reflux (GER) in dogs using standardized clinical scoring, videofluoroscopic swallow studies, and impedance planimetry. STUDY DESIGN: Prospective clinical trial. ANIMALS: A total of 17 client-owned dogs. METHODS: Dogs were included if they had clinical signs and videofluoroscopic evidence of SHH and/or GER. Owners were asked to complete a standardized canine dysphagia assessment tool (CDAT) preoperatively and postoperatively. Conscious videofluoroscopic swallowing studies and impedance planimetry (IP) were used to evaluate esophageal function and lower esophageal sphincter location and geometry preoperatively and in a subsection of dogs postoperatively. RESULTS: Preoperatively, 13/17 dogs included in the study had a history of regurgitation, and 4/17 had radiographic evidence of aspiration pneumonia. Postprandial regurgitation improved in 8/10 dogs with preoperative regurgitation, and for which completed preoperative and postoperative CDAT questionnaires were available (P < .01). The hiatal hernia severity score improved postoperatively (P = .046) in dogs with preoperative and postoperative videofluoroscopic swallowing studies (n = 12). However, hernia frequency score (P = .2) and IP parameters did not differ significantly between time points. CONCLUSION: Clinical signs of SHH generally improved with surgery but did not consistently resolve. Videofluoroscopic studies provide evidence that GER and SHH can persist postoperatively in some patients. Based on IP findings, clinical improvement may be attributed to a mechanism independent of lower esophageal sphincter attenuation.

Diagnostic outcome of contrast videofluoroscopic swallowing studies in 216 dysphagic dogs.

Determining the anatomic and functional origin for dysphagia is critical for development of an appropriate therapeutic plan and determination of the prognosis. The purpose of this retrospective study was to report the quantitative and qualitative outcome of contrast videofluoroscopic swallowing studies in a large cohort of dysphagic dogs presenting to a tertiary veterinary care hospital. The videofluoroscopic swallowing studies were reviewed to generate values for pharyngeal constriction ratio, timing of swallowing events (maximum pharyngeal contraction, opening of upper esophageal sphincter, closing of upper esophageal sphincter, and reopening of epiglottis), type of esophageal peristalsis generated, and esophageal transit time. One or more anatomic locations for origin of dysphagia were assigned (pharyngeal, cricopharyngeal, esophageal (primary motility disorder), other esophageal (stricture, vascular ring anomaly, mass), lower esophageal sphincter/hiatus. Sixty-one of 216 studies (28%) were deemed unremarkable. Twenty-seven of 216 dogs (13%) had pharyngeal dysphagia, 17/216 dogs (8%) had cricopharyngeal dysphagia, 98/216 dogs (45%) had dysphagia secondary to esophageal dysmotility, 19/216 dogs (9%) had dysphagia secondary to focal esophageal disorders, and 97/216 dogs (45%) had dysphagia of lower esophageal sphincter/hiatus origin. Multiple abnormalities were present in 82/216 (38%) dogs. Elevated pharyngeal constriction ratio was associated with pharyngeal, cricopharyngeal, and esophageal motility disorders, delayed upper esophageal sphincter opening was associated with cricopharyngeal disorders, a lower percentage of primary esophageal peristaltic waves was associated with cricopharyngeal, pharyngeal, or primary esophageal motility disorders. In conclusion, videofluoroscopic swallowing studies was pivotal in the diagnosis of dysphagia with 155/216 (72%) dogs receiving a final diagnosis.

Outcome of acute myeloid leukemia patients with pulmonary nodules of uncertain etiology receiving allogeneic hematopoietic progenitor cell transplant.

Pulmonary nodules (PNs) develop frequently in patients with acute myeloid leukemia (AML). They are of infectious or inflammatory origin. They pose potential challenges to successful hematopoietic progenitor cell (HPC) transplant as they may be niches for infection reactivation or sites susceptible to subsequent infections. We retrospectively analyzed the outcome of 20 AML patients with multiple PNs who underwent allogeneic HPC transplants (12 related, 8 unrelated). There were 13 males and seven females (median age 52 yrs). Nine patients were in CR1, seven in CR2, and four with residual disease. The median times from appearance of PNs and from last positive CT scans to transplant were three and two months, respectively. The median time from pretransplant CT scans to transplant was one month. Multiple PNs were still reported in 5/20 of the pretransplant scans. The PNs in all five patients did not worsen after transplant. Four patients (one with positive pretransplant CT scan) died within the first 100 d after transplant, but none from primary pulmonary pathology. The median survival of this group of patients was 350 d. Our results, therefore, suggest that multiple PNs of uncertain etiology in patients with AML do not impact adversely on the outcome of allogeneic HPC transplant.

Peri-transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant.

Clostridium difficile infections (CDI) remain the leading cause of infectious diarrhea among hospitalized patients in this country. Patients with hematologic malignancies, especially those who undergo hematopoietic progenitor cell transplants are particularly at risk for developing CDI. One hundred and forty seven consecutive allogeneic hematopoietic progenitor cell transplants were analyzed for peri-transplant Clostridium difficile infections (PT-CDI). Sixteen patients (11%) developed PT-CDI (Median time = 7 days after transplant). The probability for developing PT-CDI during the peri-transplant period was 12.3%. History of CDI was strongly associated with the development of PT-CDI (P = 0.008) (OR = 5.48) (P = 0.017). These patients also developed PT-CDI much earlier than in those without a history (median 1 day vs. 8 days, P = 0.03). The probability for developing PT-CDI for those with a history was 39%. There was a trend toward significance (P = 0.065) between matched related donor grafts and the development of PT-CDI (OR = 0.245) (P = 0.08). Age, sex, diagnosis, transplant preparative regimens, Graft-versus-host disease (GVHD) prophylaxis, grade 3/4 acute GVHD, or use of antimicrobials within 8 weeks of transplant were not associated with PT-CDI. Non-CDI-related deaths occurred in one patient in the PT-CDI group and nine in the group without PT-CDI. In the remaining 139 patients, the length of hospital stay for those with PT-CDI was significantly longer than those without (mean 27 days vs. 22 days; P = 0.02).

Langerhans cell histiocytosis and Erdheim-Chester disease, both with cutaneous presentations, and papillary thyroid carcinoma all harboring the BRAF(V600E) mutation.

Langerhans cell histocytosis (LCH) and Erdheim-Chester disease are two rare histiocytic disorders. Their occurrence in the same patient is more infrequent, but has been described. We report a case of a 38-year-old woman who presented with a diagnosis of single system cutaneous LCH. Subsequently, she developed multiple papules on her extremities consistent with a non-LCH xanthogranuloma type lesion. BRAF(V600E) mutation immunostain, VE1 was positive in the skin lesion, which was confirmed by molecular polymerase chain reaction (PCR) studies, initiating a complete systemic workup for Erdheim-Chester disease. Systemic involvement was confirmed with bilateral sclerotic bone lesions and retroperitoneal and pelvic fibrosing disease. She was also found to have a BRAF(V600E) mutation positive papillary thyroid carcinoma. New suspicious cutaneous lesions presenting in patients with a history of LCH need to be biopsied. A BRAF(V600E) mutation in a non-LCH histiocytic lesion with a xanthogranuloma phenotype (CD163/CD68/CD14/fascin/Factor 13a) should prompt an Erdheim-Chester disease workup. This is a unique case of a woman with BRAF(V600E) mutation positive Erdheim-Chester disease and cutaneous LCH, while also being, to our knowledge, the first reported case in the English literature of it occurring in a patient with a BRAF(V600E) mutation positive papillary thyroid carcinoma.

EFFECT OF BOLUS SIZE ON DEGLUTITION AND ESOPHAGEAL TRANSIT IN HEALTHY DOGS.

Contrast videofluoroscopy is the gold standard procedure for evaluating dysphagia in humans, but quantitative measures vary depending on bolus size and consistency. We hypothesized that quantitative measures made during videofluoroscopy of swallowing in dogs would differ between bolus sizes and consistencies. Ten healthy adult dogs were enrolled a prospective, crossover experimental study and underwent contrast videofluoroscopy while swallowing liquid (5, 10, and 15 ml) and canned food (3, 8, and 12 g) boluses. Maximum pharyngeal contraction occurred significantly later with medium solid boluses than with medium liquid boluses, with a mean difference of 0.021 s (adjusted P = 0.042). Upper esophageal sphincter opening occurred significantly earlier with large solid boluses than with medium solid boluses, with a mean difference of 0.018 s (adjusted P = 0.025). Thoracic esophageal transit time was significantly longer with small solid boluses than with small liquid boluses, with a mean difference of 0.68 s (adjusted P = 0.004). Odds of primary esophageal peristalsis occurring were significantly (18.5 times) higher with large solid vs. large liquid boluses (adjusted P = 0.031). No other statistical comparisons reached significance. Based on these results, we recommend a standardized approach to videofluoscopy in dogs with determination of quantitative measures using medium liquid and soft food boluses to minimize effects of size. Furthermore, we conclude that measurements made on liquid swallows should not be directly compared to measurements made on soft food boluses.

Total laryngectomy for management of chronic aspiration pneumonia in a myopathic dog.

A 5-month-old female pit bull terrier dog evaluated for ataxia, progressive regurgitation, and recurrent aspiration pneumonia had markedly elevated creatine kinase activity, non-inflammatory generalized myopathy, and severe esophageal dysmotility. A narrow-field total laryngectomy was performed. The dog is doing well 30 months after surgery, and no longer has episodes of aspiration pneumonia, despite intermittent regurgitation. This case represents the first application of total laryngectomy for the prevention of chronic recurrent aspiration pneumonia in the dog.

Laryngectomie totale pour la gestion d'une pneumonie par aspiration chronique chez un chien myopathique. Une chienne Pit Bull Terrier âgée de 5 mois évaluée pour de l'ataxie, de la régurgitation progressive et une pneumonie par aspiration récurrente présentait une activité de la créatine kinase particulièrement élevée, une myopathie généralisée non inflammatoire et un trouble de motilité de l'œsophage grave. Une laryngectomie totale à champ étroit a été réalisée. La chienne se porte bien 30 mois après la chirurgie et n'a plus d'épisodes de pneumonie par aspiration, malgré une régurgitation intermittente. Ce cas représente la première application d'une laryngectomie totale pour la prévention d'une pneumonie par aspiration chronique récurrente chez un chien.(Traduit par Isabelle Vallières).

LIVER ULTRASONOGRAPHY IN DOLPHINS: USE OF ULTRASONOGRAPHY TO ESTABLISH A TECHNIQUE FOR HEPATOBILIARY IMAGING AND TO EVALUATE METABOLIC DISEASE-ASSOCIATED LIVER CHANGES IN BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS).

The objective of this study was to establish a comprehensive technique for ultrasound examination of the dolphin hepatobiliary system and apply this technique to 30 dolphins to determine what, if any, sonographic changes are associated with blood-based indicators of metabolic syndrome (insulin greater than 14 µIU/ml or glucose greater than 112 mg/dl) and iron overload (transferrin saturation greater than 65%). A prospective study of individuals in a cross-sectional population with and without elevated postprandial insulin levels was performed. Twenty-nine bottlenose dolphins ( Tursiops truncatus ) in a managed collection were included in the final data analysis. An in-water ultrasound technique was developed that included detailed analysis of the liver and pancreas. Dolphins with hyperinsulinemia concentrations had larger livers compared with dolphins with nonelevated concentrations. Using stepwise, multivariate regression including blood-based indicators of metabolic syndrome in dolphins, glucose was the best predictor of and had a positive linear association with liver size (P = 0.007, R2 = 0.24). Bottlenose dolphins are susceptible to metabolic syndrome and associated complications that affect the liver, including fatty liver disease and iron overload. This study facilitated the establishment of a technique for a rapid, diagnostic, and noninvasive ultrasonographic evaluation of the dolphin liver. In addition, the study identified ultrasound-detectable hepatic changes associated primarily with elevated glucose concentration in dolphins. Future investigations will strive to detail the pathophysiological mechanisms for these changes.

Inferior outcome after allogeneic transplant in first remission in high-risk AML patients who required more than two cycles of induction therapy.

While some patients with high-risk acute myeloid leukemia (AML) require one or two cycles of induction chemotherapy to achieve a complete remission (CR), others require more than two cycles. We examined the outcomes of patients with high-risk AML who received allogeneic HPC transplant in CR1. Forty five consecutive high-risk AML patients in CR1 were included. All 45 patients had adverse cytogenetics, FLT 3 mutations, or secondary AML. Group A patients (n = 33) received one or two cycles, and Group B (n = 12) three or more cycles of induction chemotherapy. The patients were comparable in age, sex, white cell count at presentation, and time from diagnosis and from last chemotherapy to transplant. The 100-day mortality rate was higher in Group B patients (50% vs. 9%, P = 0.006). They had a higher non-relapse mortality (33% vs. 6%, P = 0.035) and a longer length of hospital stay from the day of stem cell infusion (median 21 vs. 20, P = 0.02; third quartile 22 vs. 28, P = 0.02). There was also a trend toward inferior event-free survival and overall survival. High-risk AML patients undergoing allogeneic transplant in CR1 after three or more cycles of induction chemotherapy have an inferior outcome and higher mortality when compared to those who only needed one or two cycles of induction chemotherapy. Novel strategies are needed to reduce the transplant-related mortality in high-risk AML patients needing more than two cycles of induction chemotherapy prior to allogeneic transplant in CR1.