Citations

Gut dysbiosis, host genetics, and environmental triggers are implicated as causative factors in inflammatory bowel disease (IBD), yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis (UC) patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically created blind self-filling (SFL) and self-emptying (SEL) ileal loops using wild-type (WT), IL-10 knockout (KO) (IL-10), TLR4 KO (T4), and IL-10/T4 double KO mice. After 5 wk, loop histology, host gene/protein expression, and bacterial 16s rRNA profiles were examined. SFL exhibit fecal stasis due to directional motility oriented toward the loop end, whereas SEL remain empty. In WT mice, SFL, but not SEL, develop pouchlike microbial communities without accompanying active inflammation. However, in genetically susceptible IL-10-deficient mice, SFL, but not SEL, exhibit severe inflammation and mucosal transcriptomes resembling human pouchitis. The inflammation associated with IL-10 required TLR4, as animals lacking both pathways displayed little disease. Furthermore, germ-free IL-10 mice conventionalized with SFL, but not SEL, microbiota populations develop severe colitis. These data support essential roles of stasis-induced, colon-like microbiota, TLR4-mediated colonic metaplasia, and genetic susceptibility in the development of pouchitis and possibly UC. However, these factors by themselves are not sufficient. Similarities between this model and human UC/pouchitis provide opportunities for gaining insights into the mechanistic basis of IBD and for identification of targets for novel preventative and therapeutic interventions.

Twenty volunteers with normal noses were studied to determine the effect of phenylephrine on nasal ciliary function. In vivo study of this drug was performed in 15 patients and revealed a significant increase in their ciliary beat frequency from a control of 11 Hz to 12.03 Hz (p = 0.001). Mucociliary transit times in these volunteers were also studied, revealing a mean of 9.9 minutes prestimulation and 10.2 minutes poststimulation, which was not statistically significant (p = 0.77). Five additional subjects donated ciliated mucosal samples for in vitro analysis of varying concentrations of this agent that showed a significant ciliostimulatory effect at lower concentrations (0.01%), with a progressive cilioinhibitory effect at higher concentrations (0.25%, 0.5%). The 0.05% concentration showed no significant change in ciliary activity compared to control measurements. These data demonstrate that phenylephrine has a ciliostimulatory effect in vivo, as well as in appropriate concentrations in vitro, and should be safe and relatively nontoxic to the mucociliary apparatus for short‐term use.3

A 39-year-old male, who recently underwent a composite valve graft of the aortic root and ascending aorta for bicuspid aortic valve and aortic root aneurysm, was hospitalized for severe sepsis, rhabdomyolysis (creatine kinase 29000 U/L), and severe liver dysfunction (AST > 7000 U/L, ALT 4228 U/L, and INR > 10). Cardiac magnetic resonance imaging (MRI) findings were consistent with sternal osteomyelitis with a 1.5 cm abscess at the inferior sternotomy margin, which was contiguous with pericardial thickening. Aspiration and culture of this abscess did not yield any organisms, so he was treated with vancomycin and cefepime empirically for 4 weeks. Because this patient was improving clinically on antibiotics and did not show external signs of wound infection, there was no compelling indication for sternectomy. This patient’s unusual presentation with osteomyelitis and rhabdomyolysis has never been reported and is crucial for clinicians to recognize in order to prevent delays in diagnosis.

Photoplethysmography was used to evaluate 14 skin flaps in the pig. Eight skin flaps were 4×12 cm and were based dorsally. Six skin flaps were 4×18 cm and were based ventrally. All flaps were designed to undergo necrosis of the distal end. After elevation of the flap, blood flow to the skin flaps was estimated immediately by means of intravenously administered fluorescein. Photoplethysmography was used to determine blood flow to the skin flaps at 3, 24, 72, and 144 hours after elevation. Surviving length of the skin flaps was measured at nine days. Fluorescein accurately predicted the surviving length of the skin flaps. Photoplethysmography did not show a decrease in blood flow at the level of fluorescein penetration 3 or 48 hours after elevation. However, 72 and 144 hours after elevation, an abrupt decrease in blood flow was noted by photoplethysmography at the level of eventual skin necrosis.

Photoplethysmography was used to evaluate 14 skin flaps in the pig. Eight skin flaps were 4×12 cm and were based dorsally. Six skin flaps were 4×18 cm and were based ventrally. All flaps were designed to undergo necrosis of the distal end. After elevation of the flap, blood flow to the skin flaps was estimated immediately by means of intravenously administered fluorescein. Photoplethysmography was used to determine blood flow to the skin flaps at 3, 24, 72, and 144 hours after elevation. Surviving length of the skin flaps was measured at nine days. Fluorescein accurately predicted the surviving length of the skin flaps. Photoplethysmography did not show a decrease in blood flow at the level of fluorescein penetration 3 or 48 hours after elevation. However, 72 and 144 hours after elevation, an abrupt decrease in blood flow was noted by photoplethysmography at the level of eventual skin necrosis.

Disturbance of the normal relationship between the caudal border of the upper lateral cartilage and the cephalic margin of the lobular cartilage—the so‐called “cul‐de‐sac” area—can result in alar collapse and nasal airway obstruction. This may be caused by either the aging process or trauma, both surgical and nonsurgical. Rhinolift is a surgical procedure that was developed for the treatment of the aging ptotic nasal tip. We have applied this technique to patients with nasal airway obstruction resulting from alar collapse. Elevation of the cephalic margin of the lobular cartilage to a position superficial to the upper lateral cartilage restores the normal relationship between these two structures. The upper lateral cartilage then assists in stenting the vestibule open, and thereby improves nasal breathing. Over the past 10 years, 20 patients have had rhinolifts at our institution for the relief of nasal airway obstruction. Concomitant surgery included nasal septal reconstruction in 12 patients, polypectomy in one patient, and placement of a silicone rubber septal prosthesis for closure of a large septal perforation in three patients. Rhinolift was the sole procedure used for the correction of valvular pathology in 10 patients. The other 10 patients had modifications made in their upper lateral cartilage along with the rhinolift. Five patients described restoration of normal nasal breathing, while 14 patients showed partial symptomatic improvement. One patient reported no improvement in nasal breathing. Rhinolift is a safe effective surgical technique for functional improvement of nasal breathing in patients with alar collapse resulting from inadequate cartilaginous support.

A new computerized technique for the assessment of human nasal ciliary beat frequency is described. Thirty normal volunteers underwent nasal cytologic brushing to obtain ciliary samples. In each subject, 150 ciliary beats were analyzed from each of 50 separate ciliated cell clusters. The ciliary beat frequency for each area was determined with fast Fourier transformation. The results were plotted on a histogram to determine the ciliary beat distribution. The mean frequency for these samples was 11.29 Hz, with a standard deviation of 0.96 Hz. The median frequency for these samples was 11.25 Hz. These results show a marked improvement over hand‐counting microphotometry techniques because of the much larger sampling size and elimination of much human error. We believe this method of ciliary analysis represents a significant advancement in the evaluation of ciliary function and should assist in the diagnosis of patients with congenital and acquired forms of ciliary dysmotility.

AbstractBackgroundThe optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non‐influenza respiratory viruses in Midwestern transplant centers.MethodsA survey assessing strategies for RSV and other non‐influenza respiratory viral infections was sent to 13 centers.ResultsMultiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post‐stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft‐versus‐host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non‐lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non‐lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus.ConclusionsTreatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts.