Trilokesh D. Kidambi

A Rapid Murine Coma and Behavior Scale for Quantitative Assessment of Murine Cerebral Malaria

Background Cerebral malaria (CM) is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM) models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. Methodology/Principal Findings A quantitative, rapid murine coma and behavior scale (RMCBS) comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. Conclusions/Significance Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field). The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

Tricuspid valve repair with left ventricular assist device implantation: is it warranted?

BACKGROUND Tricuspid regurgitation is common in patients with advanced heart failure. The ideal operative strategy for managing tricuspid valve regurgitation (TR) in patients undergoing left ventricular assist device (LVAD) implantation is unclear. This study was designed to evaluate the effect on outcomes of concomitant tricuspid valve repair (TVR) for moderate to severe (3(+)/4(+)) TR at the time of LVAD implantation. METHODS Patients with >3(+) TR who underwent LVAD implantation from 2005 to 2009 were retrospectively evaluated. Pre-, intra- and post-operative data, including hemodynamics, inotrope requirements and end-organ function parameters, were considered. Outcomes of patients receiving TVR were compared with those who did not receive TVR (NTVR). RESULTS Seventy-two LVADs were implanted during the study period. Forty-two (58%) patients had ≥ 3(+) TR prior to LVAD implantation. Eight patients underwent TVR and 34 patients did not undergo TVR (NTVR). There were no significant differences in baseline characteristics or severity of TR between the two groups. The TVR group had a longer cardiopulmonary bypass time (p < 0.01) and required more blood products (p < 0.05). Higher post-operative creatinine and blood urea nitrogen (BUN) values were noted in the TVR group. One patient in the TVR group and 3 patients in the NTVR group required right-sided mechanical assistance (p = 0.6). There was no significant difference in short- or long-term mortality between the two groups. CONCLUSIONS TVR for ≥ 3(+) TR prolonged operative time and showed similar outcomes compared with LVAD implantation alone. A benefit of performing TVR was not demonstrated. As such, TVR may not be necessary at the time of LVAD implantation.

Temporal trends in the relative prevalence of dysphagia etiologies from 1999-2009

AIM To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy (EGD) over the past decade. METHODS EGDs with the indication of dysphagia at an urban, university medical center in 1999, 2004 and 2009 were retrospectively identified from the electronic medical record. The entire patient chart, including EGD, pathology, manometry, radiographic and clinician reports, was reviewed for demographic and clinical data and to determine the etiology of dysphagia. The number of EGDs in which an esophageal biopsy was performed was also noted. Gastroesophageal reflux disease (GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition (PPI). Cases of eosinophilic esophagitis (EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field. PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008. Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999, 2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect. RESULTS A total of 1371 cases (mean age 54 years, 43% male) met pre-specified inclusion criteria with 191, 504 and 675 cases in 1999, 2004 and 2009, respectively. Patients were older in 2004 compared to 2009 (mean ± SD, 54.0 ± 15.7 years vs 52.3 ± 16.8 years, P = 0.02) and there were more males in 1999 compared to 2004 (57.5% vs 40.8%, P = 0.005). Overall, GERD (27.6%) and EoE (7.7%) were the most common identifiable causes of dysphagia. An unspecified diagnosis accounted for 21% of overall cases. There were no significant differences in the relative prevalence of achalasia or other motility disorders, peptic stricture, Schatzkis ring, esophageal cancer or unspecified diagnoses over the 10-year time period. There was, however, a decrease in the relative prevalence of GERD (39.3% vs 24.1%, P < 0.001) and increases in the relative prevalence of EoE (1.6% vs 11.2%, P < 0.001) and oropharyngeal disorders (1.6% vs 4.2%, P = 0.02) from 1999 to 2009. Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009 (5.4% vs 11.6%, P < 0.001), but not between 1999 and 2004 (1.6% P 5.4%, P = 0.21). On the other hand, the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004 (39.3% vs 27.7%, P = 0.006), but not between 2004 and 2009 (27.7% vs 24.1%, P = 0.36). There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009 (36.7% vs 68.7%, P < 0.001) as well as between 2004 and 2009 (37.5% vs 68.7%, P < 0.001). While total EGD volume did increase over the 10-year time period, the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE. CONCLUSION EoE has emerged as a dominant cause of dysphagia in adults. Whether this was due to a rise in disease incidence or increased recognition is unclear.

Congenital sialolipoma of the parotid gland: presentation, diagnosis, and management☆☆☆

Congenital sialolipoma of the parotid gland: presentation, diagnosis, and management Trilokesh Kidambi, BA, Mark J. Been, MD, John Maddalozzo, MD, FACS, FAAP⁎ Northwestern University, Feinberg School of Medicine, Chicago, IL, USA Division of Otolargynology, Department of Surgery, University of Illinois College of Medicine at Chicago, Chicago, IL, USA Division of Pediatric Otolargynology, Department of Surgery, Childrens Memorial Hospital, Chicago, IL, USA Received 17 June 2011

Cholangiocarcinoma Presenting as Metastases to the Cervical Spine

0002-9343/

Screening for Lynch Syndrome: It Is Time to Shift the Focus

-see front matter

Endoscopy is of low yield in the identification of gastrointestinal neoplasia in patients with dermatomyositis: A cross-sectional study

To the Editor, We read with interest the study by Gould-Suarez et al. [1] and the accompanying editorial by Ladabaum [2]. The authors performed a decision analytic modeling study comparing the cost-effectiveness of 10 strategies to diagnose Lynch syndrome (LS) in colorectal cancer (CRC) patients and concluded that strategies relying on laboratory-based tests were more cost-effective than a revised Bethesda-guideline-based approach. The authors should be lauded for adding a valuable study to the existing literature on cost-effectiveness of screening for LS [3, 4], but a few issues deserve mention. Despite a call for universal screening [5], there is no standard protocol for selection of patients to screen [6] and recent guidelines support screening patients with CRC under the age of 70 years or with traditional testing indications [7]. Surprisingly, a strategy utilizing this age cutoff was not modeled in this study. Estimates of using an age cutoff of 70 years predict that the number of screened cases would be reduced by 49 %, while 91 % of LS cases would remain included in the screened cohort with only 0.5 % of cases (in absolute numbers: 68 patients in this hypothetical study) excluded in the unscreened cohort [4, 8]. If this were applied to the decision model, then in strategy 1 the detection rate would decrease to 82.4 % with a mean cost per LS of

Lower gastrointestinal neuroendocrine neoplasms associated with hereditary cancer syndromes: a case series

30,154, while strategy 5 (the most expensive) would have a detection rate of 90.5 % with a mean cost per LS of

Differences in neuropsychological and behavioral parameters and brain structure in patients with familial adenomatous polyposis: a sibling-paired study

111,841. Imposing this age cutoff would therefore significantly lower costs at the expense of a modest decrease in detection rate, which may be a reasonable trade-off in a resource-limited setting. In fact, the implementation of exactly this screening approach has already been reported [9]. The most critical factor overlooked in this study was regarding patient follow-up for an abnormal screening test. The authors assumed that all patients with abnormal screens would undergo germ line testing, which in published studies of LS implementation in US clinical settings have ranged widely from 26 to 83 %, depending on the specific implementation model [9–11]. This would clearly affect the analysis as the incremental cost-effectiveness ratio would increase drastically as fewer patients with positive screening tests undergo germ line testing. Furthermore, in our own experience [11], we observed a nonstatistically significant trend toward fewer patients in a universally screened approach following up with germ line testing compared with those in a selective, Bethesda-based approach. This observation needs further investigation and, if confirmed, may have important implications for the implementation of universal screening. In the future, models must take into account more accurate assumptions regarding the loss to follow-up and patients’ decisions to not undergo germ line testing as this impacts the cost calculations and also has important implications for the identification of probands and their relatives. Ultimately, rather than focusing on who to screen, the focus should shift to investigating implementation strategies with high-quality screening in an effort to identify all patients with LS. T. D. Kidambi (&) Department of Internal Medicine, University of California, San Francisco, 505 Parnassus Avenue, Room 987, San Francisco, CA 94143, USA e-mail: Trilokesh.Kidambi@ucsf.edu

MRSA-Associated Lemierre’s Syndrome in an Intravenous Drug User

AIM To determine the prevalence of gastrointestinal neoplasia among dermatomyositis patients who underwent an esophagogastroduodenoscopy and/or colonoscopy. METHODS A cross-sectional study examining the results of upper endoscopy and colonoscopy in adults with dermatomyositis at an urban, university hospital over a ten year period was performed. Chart review was performed to confirm the diagnosis of dermatomyositis. Findings on endoscopy were collected and statistical analyses stratified by age and presence of symptoms were performed. RESULTS Among 373 adult patients identified through a code based search strategy, only 163 patients had dermatomyositis confirmed by chart review. Of the 47 patients who underwent upper endoscopy, two cases of Barrett’s esophagus without dysplasia were identified and there were no cases of malignancy. Of the 67 patients who underwent colonoscopy, no cases of malignancy were identified and an adenoma was identified in 15% of cases. No significant differences were identified in the yield of endoscopy when stratified by age or presence of symptoms. CONCLUSION The yield of endoscopy is low in patients with dermatomyositis and is likely similar to the general population; we identified no cases of malignancy. A code based search strategy is inaccurate for the diagnosis of dermatomyositis, calling into question the results of prior population-based studies. Larger studies with rigorously validated search strategies are necessary to understand the risk of gastrointestinal malignancy in patients with dermatomyositis.