Kristina J. Liu

Report of two cases

Two patients underwent thoracotomy for resection of pulmonary or esophageal carcinoma. Postoperatively, epidural catheters were inserted for pain management. Complaints of severe injection pain over the abdomen or lower extremities were made during one administration of pain medication. Progressive weakness and numbness developed over the lower trunk and lower extremities, with subsequent respiratory difficulties. Potassium chloride (KCl) was suspected to have been mistaken for normal saline as the diluent for morphine. In addition to endotracheal intubation and ventilatory support, steroids were administered both intravenously and epidurally to suppress spinal cord irritation. The two patients regained motor and sensory functions 14 and 18 hours later, respectively, without sequelae.

Genomic landscape of cutaneous T cell lymphoma.

Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes. We performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL and matched normal cells. The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NF-κB signaling, chromatin remodeling and DNA damage response. CTCL is distinctive in that somatic copy number variants (SCNVs) comprise 92% of all driver mutations (mean of 11.8 pathogenic SCNVs versus 1.0 somatic single-nucleotide variant per CTCL). These findings have implications for new therapeutics.

Antiobesity and Antihyperglycemic Effects of Ginsenoside Rb1 in Rats

OBJECTIVE Obesity and type 2 diabetes are national and worldwide epidemics. Because currently available antiobesity and antidiabetic drugs have limited efficacy and/or safety concerns, identifying new medicinal agents, such as ginsenoside Rb1 (Rb1) as reported here, offers exciting possibilities for future development of successful antiobesity and antidiabetic therapies. RESEARCH DESIGN AND METHODS Changes in feeding behavior after acute intraperitoneal administration of Rb1 and the effects of intraperitoneal Rb1 for 4 weeks on body weight, energy expenditure, and glucose tolerance in high-fat diet (HFD)-induced obese rats were assessed. We also examined the effects of Rb1 on signaling pathways and neuropeptides in the hypothalamus. RESULTS Acute intraperitoneal Rb1 dose-dependently suppressed food intake without eliciting signs of toxicity. This inhibitory effect on feeding may be mediated by central mechanisms because Rb1 stimulated c-Fos expression in brain areas involved in energy homeostasis. Consistent with this, Rb1 activated the phosphatidylinositol 3-kinase/Akt signaling pathway and inhibited NPY gene expression in the hypothalamus. Four-week administration of Rb1 significantly reduced food intake, body weight gain, and body fat content and increased energy expenditure in HFD-induced obese rats. Rb1 also significantly decreased fasting blood glucose and improved glucose tolerance, and these effects were greater than those observed in pair-fed rats, suggesting that although Rb1s antihyperglycemic effect is partially attributable to reduced food intake and body weight; there may be additional effects of Rb1 on glucose homeostasis. CONCLUSIONS These results identify Rb1 as an antiobesity and antihyperglycemic agent.

Atypical hand-foot-and-mouth disease associated with coxsackievirus A6 infection

BACKGROUND Hand-foot-and-mouth disease (HFMD) is an acute viral illness commonly caused by coxsackievirus (CV)-A16 and enterovirus 71 infections. Recently, atypical HFMD has been reported in association with CV-A6, an uncommon enterovirus strain. OBJECTIVE We sought to describe the clinical features of atypical HFMD associated with CV-A6 infection and its diagnostic laboratory evaluation. METHODS Patients presenting to our institution with history and examination suggestive of atypical HFMD from January 2012 to July 2012 were identified. Morphology and distribution of mucocutaneous lesions were recorded. Enterovirus infection was assessed by reverse transcriptase polymerase chain reaction of biologic specimens. Enterovirus type was determined by viral capsid protein 1 gene sequencing. RESULTS Two adults and 3 children with atypical HFMD were identified. Four of 5 patients exhibited widespread cutaneous lesions. In 2 patients with a history of atopic dermatitis, accentuation in areas of dermatitis was noted. Associated systemic symptoms prompted 4 of 5 patients to seek emergency care, and both adults were hospitalized for diagnostic evaluation. Infection with CV-A6 was confirmed in all patients. LIMITATIONS This study is a case series from a single institution. CONCLUSION Consideration of the expanded range of cutaneous findings in atypical HFMD caused by CV-A6 infection may assist clinicians in diagnosis and management.

Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors and represents a failure of biliary cholesterol homoeostasis in which the physical–chemical balance of cholesterol solubility in bile is disturbed.

Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vβ chain restriction

BACKGROUND Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden. OBJECTIVE We sought to determine the spectrum of current clinical practices; critically evaluate elements of current International Society for Cutaneous Lymphomas (ISCL) B1 and B2 staging criteria; and assess the potential role of T-cell receptor-Vβ analysis by flow cytometry. METHODS We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, positive predictive value, and negative predictive value of parameters for ISCL B2 staging. RESULTS There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture 5 Yale cohort cases with immunophenotypic abnormalities that later progressed. T-cell receptor-Vβ testing was more specific than polymerase chain reaction and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. LIMITATIONS Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. CONCLUSION We propose further study of modified B1 criteria: CD4/CD8 ratio 5 or greater, %CD4(+) CD26(-) 20% or greater, or %CD4(+) CD7(-) 20% or greater, with evidence of clonality. T-cell receptor-Vβ testing should be considered in future diagnostic and staging algorithms.

Experimental Model of Trigger Finger Through A1 Pulley Constriction in a Human Cadaveric Hand: A Pilot Study

PURPOSE Although it can be reasonably assumed that trigger digits occur as the result of a size mismatch in the pulley-tendon system, it is unclear whether locking, histological changes, and nodule formation occur owing to an intrinsically too small pulley or an enlarged digital flexor tendon. Our purposes in this feasibility study were to (1) create a model of trigger digit by pulley constriction in nonpreserved human tissue, (2) measure the change in work of flexion as the force of pulley constriction increased, (3) compare the work of flexion between nontriggering and triggering conditions, and (4) determine whether triggering can occur at the A2, A3, and A4 pulleys under similar conditions. METHODS Using a tensiometer, we studied the work of flexion in 4 fingers (thumb, index, middle, and ring) in a human cadaveric hand. The load of flexion was measured as the A1 to A4 pulleys were incrementally constricted in order to induce triggering. Work of flexion was analyzed for differences among trial conditions. RESULTS Triggering was successfully induced in all 4 digits through constriction of the A1 pulley. No triggering occurred in any of the A2, A3, or A4 pulley systems in this model. CONCLUSIONS We successfully created a trigger model in a human cadaveric hand. Our results demonstrate that the A1 pulley can cause triggering from manual constriction of the pulley alone. CLINICAL RELEVANCE A trigger model such as this may allow investigations of pathophysiology, and this may result in novel treatment strategies and modalities.

Risk of Developing Pyoderma Gangrenosum after Procedures in Patients with a Known History of Pyoderma Gangrenosum – A Retrospective Analysis

Background The risk of postoperative pyoderma gangrenosum (PG) in patients with a known history of PG is unknown. Objective To quantify risk and identify patient‐ and/or procedure‐related risk factors for postsurgical recurrence or exacerbation of PG in patients with a known history of PG. Methods We retrospectively evaluated the likelihood of postsurgical recurrence or exacerbation of PG for all patients with a confirmed diagnosis of PG at Brigham and Womens Hospital and Massachusetts General Hospital from 2000 to 2015. Results In all, 5.5% of procedures (n = 33) led to recurrence of PG in 15.1% of patients (n = 25). Compared with skin biopsy, small open surgical procedures had an adjusted odds ratio (aOR) of 8.65 (95% confidence interval [CI], 1.55‐48.33) for PG recurrence or exacerbation; large open surgical procedures had an aOR of 5.97 (95% CI, 1.70‐21.00); and Mohs micrographic surgery/skin excision had an aOR of 6.47 (95% CI, 1.77‐23.61). PG chronically present at the time of the procedure had an aOR of 4.58 (95% CI, 1.72‐12.22). Immunosuppression, time elapsed since the original PG diagnosis, and procedure location did not significantly influence risk. Limitations Our study is limited by its retrospective nature and relatively small sample size. Conclusion There is a small but clinically meaningful risk for postsurgical recurrence or exacerbation of PG in patients with a known history of PG; higher risks occur with more invasive procedures and chronically present PG.

Successful Use of Cyclosporin A for Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis in Three Children

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are medical emergencies. Mainstays of treatment include removal of the offending agent, supportive care, and wound care. The use of immunosuppressive agents such as corticosteroids and intravenous immunoglobulin (IVIg) is controversial. Some case reports and small studies report the successful use of cyclosporin A (CsA) for SJS/TEN in halting disease progression, fostering reepithelialization, and reducing mortality.

Modeling the Effect of Shared Care to Optimize Acne Referrals From Primary Care Clinicians to Dermatologists

IMPORTANCE Access to dermatologists remains a nationwide challenge. Optimizing referrals to a dermatologist may reduce patient wait times. OBJECTIVE To model the effect of algorithm-based acne treatment by primary care clinicians on referral patterns and costs. DESIGN, SETTING, AND PARTICIPANTS Overall, 253 referrals from primary care clinicians to dermatologists for acne from January 2014 through March 2015 were reviewed at Brigham and Womens Hospital. No-show rate, diagnostic concordance between primary care clinicians and dermatologists, treatment at the time of referral, and treatment by a dermatologist were ascertained, and we modeled 2 treatment algorithms-initiation of topical treatments by primary care clinicians (algorithm A) and initiation of topical treatments and oral antibiotics by primary care clinicians (algorithm B)-to identify the most effective referral patterns and costs. MAIN OUTCOMES AND MEASURES The primary outcome was the elimination of unnecessary appointments with a dermatologist. Secondary outcomes included reduction in delay to treatment, health care cost savings, and decrease in no-show rate. RESULTS Overall, 150 of 253 referred patients were seen and treated by a dermatologist; 127 patients (50.2%) were not on prescription acne treatment at the time of dermatology referral. Model A reduced initial referrals in 72 of 150 cases (48.0%), eliminated referrals in 60 of 150 cases (40%), and reduced average delay-to-treatment by 28.6 days. This resulted in cost savings of