Recent Publications by CFE Educators

HIV-mediated immune dysfunction may influence CD4(+) T cell recovery during suppressive antiretroviral therapy (ART). We analyzed cellular biomarkers of immunological inflammation, maturation, and senescence in HIV-infected subjects on early suppressive ART. We performed longitudinal analyses of peripheral immunological biomarkers of subjects on suppressive ART (n = 24) from early treatment (median 6.4 months, interquartile range [IQR] 4.8-13.9 months) to 1-2 years of follow-up (median 19.8 months, IQR 18.3-24.6 months). We performed multivariate regression to determine which biomarkers were associated with and/or predictive of CD4(+) T cell recovery. After adjusting for the pre-ART CD4(+) T cell count, age, proximal CD4(+) T cell count, and length of ART medication, the percentage of CD27(+)CD8(+) T cells remained significantly associated with the CD4(+) T cell recovery rate (β = 0.092 cells/ul/month, P = 0.028). In HIV-infected subjects starting suppressive ART, patients with the highest percentage of CD8(+) T cells expressing CD27 had the greatest rate of CD4(+) T cell recovery.

BACKGROUND

En bloc resection of the superior mesenteric vein (SMV), portal vein (PV), and/or splenic vein (SV) with concomitant venous reconstruction is required in 11-65 % of cases of locally advanced pancreatic cancer.1 Early retropancreatic dissection of the superior mesenteric artery (SMA) from behind the pancreatic head utilizing an 'artery first' approach has been reported to be an efficient and safe approach to pancreaticoduodenectomy when SMA involvement is suspected.2 Additionally, this technique has been shown to reduce blood loss and result in shorter PV clamp times.3 While there are multiple variations to 'artery first' resection,4 this video will illustrate the critical steps of using the 'posterior approach' in patients with locally advanced pancreatic cancer. This approach has the benefit of early identification of a replaced right hepatic artery, but may be difficult in obese patients or those with extensive peripancreatic inflammation. These difficulties may be overcome by utilizing an 'inferior supracolic (anterior) approach', but this necessitates early division of the pancreatic neck and stomach.5 METHODS: Select video clips were compiled from several pancreatoduodenectomies to demonstrate this technique. A variety of bipolar devices were utilized for dissection depending on surgeon preference. All patients were diagnosed with locally advanced pancreatic cancer by Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology (AHPBA/SSO) consensus criteria, confirmed by biopsy, and completed neoadjuvant chemotherapy. Patients were restaged by pancreas protocol computed tomography scan at the end of chemotherapy and offered local resection if the tumor did not progress and they were medically fit. No Institutional Review Board approval was required.

RESULTS

The operation begins by dividing the attachment of the transverse mesocolon to the right perinephric area and extending this down to the white line of Toldt, followed by a wide Kocher maneuver. The lateral attachments to the pancreatic head are then divided, thereby exposing the left renal vein. The lesser sac is entered directly over the uncinate, allowing for a full visceral rotation of the pancreatic head, and further facilitating exposure of the left renal vein. In the setting of malignancy, the SMA may now be palpated posterior to the pancreatic head and/or neck to confirm it is free of tumor. If tumor is invading the SMA, the pancreaticoduodenectomy is aborted prior to performing any gastrointestinal or pancreatic transections. If the SMA is free, the dissection is then carried on to the inferior aspect of the pancreatic neck. Here the SMV (jejunal and ileal branches), middle colic vein, and the gastroepiploic vein are identified and the latter is ligated and transected. Following this, dissection of the portal structures (hepatic arteries, gastroduodenal artery, common bile duct, and PV) is performed. The jejunum is then divided, the ligament of Treitz is taken down, and the jejunum is then mobilized to the patient's right side. This allows for clear visualization of the pancreatic head/uncinate/SMV relationship. At this point, proximal and distal control of the PV, SMV, and SV should be obtained using vessel loops or umbilical tape. The dissection then proceeds laterally along the SMA border (posterior to the pancreatic head). This is often facilitated by use of a bipolar sealing device due to a rich lymphovascular network. Once the lateral border of the SMA is clearly exposed, dissection along its longitudinal axis is performed utilizing the jejunum for traction. Following this dissection, larger vessels such as the inferior pancreaticoduodenal artery can be more readily identified and ligated to fully mobilize the pancreatic head. After the head is completely separated from the SMA, the neck is divided. This leaves the specimen attached solely by the PV and SMV, which greatly facilitates venous resection and reconstruction when necessary.

CONCLUSION

The 'artery first' approach has been shown to be safe and feasible in pancreatic resections. This technique should be considered whenever tumor is thought to involve the SMV and/or PVs as a means to facilitate safe venous resection and reconstruction while preserving sound oncologic principles.

BACKGROUND

Although the cytokine IL-31 has been implicated in inflammatory and lymphoma-associated itch, the cellular basis for its pruritic action is yet unclear.

OBJECTIVE

We sought to determine whether immune cell-derived IL-31 directly stimulates sensory neurons and to identify the molecular basis of IL-31-induced itch.

METHODS

We used immunohistochemistry and quantitative real-time PCR to determine IL-31 expression levels in mice and human subjects. Immunohistochemistry, immunofluorescence, quantitative real-time PCR, in vivo pharmacology, Western blotting, single-cell calcium imaging, and electrophysiology were used to examine the distribution, functionality, and cellular basis of the neuronal IL-31 receptor α in mice and human subjects.

RESULTS

Among all immune and resident skin cells examined, IL-31 was predominantly produced by TH2 and, to a significantly lesser extent, mature dendritic cells. Cutaneous and intrathecal injections of IL-31 evoked intense itch, and its concentrations increased significantly in murine atopy-like dermatitis skin. Both human and mouse dorsal root ganglia neurons express IL-31RA, largely in neurons that coexpress transient receptor potential cation channel vanilloid subtype 1 (TRPV1). IL-31-induced itch was significantly reduced in TRPV1-deficient and transient receptor channel potential cation channel ankyrin subtype 1 (TRPA1)-deficient mice but not in c-kit or proteinase-activated receptor 2 mice. In cultured primary sensory neurons IL-31 triggered Ca(2+) release and extracellular signal-regulated kinase 1/2 phosphorylation, inhibition of which blocked IL-31 signaling in vitro and reduced IL-31-induced scratching in vivo.

CONCLUSION

IL-31RA is a functional receptor expressed by a small subpopulation of IL-31RA(+)/TRPV1(+)/TRPA1(+) neurons and is a critical neuroimmune link between TH2 cells and sensory nerves for the generation of T cell-mediated itch. Thus targeting neuronal IL-31RA might be effective in the management of TH2-mediated itch, including atopic dermatitis and cutaneous T-cell lymphoma.

Male urethral stricture disease is prevalent and has a substantial impact on quality of life and health-care costs. Management of urethral strictures is complex and depends on the characteristics of the stricture. Data show that there is no difference between urethral dilation and internal urethrotomy in terms of long-term outcomes; success rates range widely from 8-80%, with long-term success rates of 20-30%. For both of these procedures, the risk of recurrence is greater for men with longer strictures, penile urethral strictures, multiple strictures, presence of infection, or history of prior procedures. Analysis has shown that repeated use of urethrotomy is not clinically effective or cost-effective in these patients. Long-term success rates are higher for surgical reconstruction with urethroplasty, with most studies showing success rates of 85-90%. Many techniques have been utilized for urethroplasty, depending on the location, length, and character of the stricture. Successful management of urethral strictures requires detailed knowledge of anatomy, pathophysiology, proper patient selection, and reconstructive techniques.

PURPOSE

We examine the association among depression, suicidal ideation and self-reported lower urinary tract symptoms using a large, cross-sectional, population based study.

MATERIALS AND METHODS

The study included 2,890 men from the 2005-2006 or 2007-2008 cycles of the NHANES (National Health and Nutrition Examination Survey) who were 40 years old or older. Men were asked if they experienced nocturia, urinary hesitancy and/or incomplete bladder emptying. The PHQ-9 (Patient Health Questionnaire-9) was used to determine the likelihood of clinical depression and suicidal ideation.

RESULTS

The prevalence of lower urinary tract symptoms was 33.7% and 10.3% for men reporting 1 and 2 or more symptoms, respectively. Moderate to severe depression (PHQ-9 score 10 or greater) and suicidal ideation were reported by 181 (6.3%) and 105 (3.6%) men, respectively. Men reporting moderate to severe depression (compared to those reporting minimal depression) had a higher odds of reporting lower urinary tract symptoms (adjusted odds ratio [AOR] 5.09, 95% CI 3.17-8.17 for PHQ-9 score 5 to 9 and AOR 7.62, 95% CI 3.90-14.87 for PHQ-9 score 10 or greater; p trend 0.0001). More lower urinary tract symptoms were associated with a significantly higher odds of moderate to severe depression (AOR 3.09, 95% CI 1.86-5.15 for 1 symptom and AOR 8.06, 95% CI 4.18-15.53 for 2 or more symptoms, p trend 0.0001) and a higher odds of suicidal ideation (AOR 1.70, 95% CI 0.85-3.42 and AOR 2.71, 95% CI 1.40-5.25, respectively, p trend = 0.004).

CONCLUSIONS

A significant relationship was observed between lower urinary tract symptoms and depression/suicidal ideation. While the pathophysiology of the relationship and its significance in clinical practice remain unclear, clinicians may consider screening men with severe lower urinary tract symptoms for depression.

BACKGROUND

There is a paucity of data examining the epidemiology of recipients of multiple in-hospital cardiopulmonary resuscitation (CPR) attempts, and their outcomes.

METHODS

There is a paucity of data examining the epidemiology of recipients of multiple in-hospital cardiopulmonary resuscitation (CPR) attempts, and their outcomes.

DATA SOURCE

Nationwide Inpatient Sample, 2000 to 2009. Patient characteristics, survival to discharge, discharge disposition, and cost of hospitalization of patients who had 1 versus multiple (>1) CPR attempts were compared using bivariate and multivariate methods.

RESULTS

Of 166,519 hospitalized CPR recipients, 3.4% had multiple CPR attempts. Compared with 1-time CPR recipients, those undergoing multiple CPR were younger (age 65 years; 37.3% vs 42.5%, respectively), more often nonwhite (34.2% vs 41.4%), and commonly treated in nonteaching hospitals (58.0% vs 64.5%; all P  0.001). Survival to discharge decreased by >40% for each additional CPR attempt (23.4% vs 11.9%, and 6.7% for 1, 2, and ≥3 CPR attempts, respectively; P  0.001). After multivariate adjustment, multiple CPR was independently associated with a lower survival to discharge (odds ratio: 0.41, 95% confidence interval: 0.37-0.44, P  0.001). Recipients of multiple CPR were more likely to be discharged to destinations other than home (80.7% vs 70.1%, P  0.001); 1 in 15 survivors of multiple CPR were discharged to hospice (6.8%), compared with 1 in 23 patients (4.3%) who had 1 CPR (P = 0.002). The average cost per day of hospitalization was higher for patients who had multiple CPR versus 1 CPR ($4484.60 vs $3581.40, P  0.001).

CONCLUSIONS

Recipients of multiple in-hospital CPR attempts are more likely to be younger, nonwhite, and treated in nonteaching hospitals. Survival to discharge is significantly worse, and the cost of hospitalization is considerably higher for these patients.

We present a case of a patient with xanthogranulomatous pyelonephritis (XGP) presenting with a large (18 × 12 cm) left-sided flank mass with worsening left flank pain. CT abdomen/pelvis demonstrated a left kidney with parenchyma replaced by multiple large hypodense collections containing fluid and gas, a left staghorn calculus, and a communication between the kidney and large flank collection. About 4.5 weeks after initial presentation, the patient underwent operative intervention. Pathology revealed an end-stage kidney with scar consistent with xanthogranulomatous pyelonephritis.

IMPORTANCE

Children with poor muscle tone may demonstrate upper airway obstruction due to several mechanisms including obstructive sleep apnea, laryngopharyngeal reflux, and laryngomalacia. Though hypotonia has been shown to compromise the pediatric airway, and some authors suggest that neurologic deficits can compromise the success of laryngotracheal reconstruction (LTR), to our knowledge no studies have evaluated the effect of neurologic diagnoses or hypotonia on outcomes in LTR.

OBJECTIVE

To determine whether hypotonic children with subglottic stenosis have lower rates of successful decannulation after LTR compared with children without neurologic deficit.

DESIGN, SETTING, AND PARTICIPANTS

A retrospective medical chart review was conducted for 27 children aged 0 to 6 years, who underwent LTR for subglottic stenosis between December 2007 and December 2012 at a tertiary care children's hospital. Children were classified based on documented neurologic findings. Group 1 comprised those children without neurologic impairment (n = 16). Group 2 included those children with a documented neurocognitive or neuromuscular diagnosis but without evidence of hypotonia (n = 7). Group 3 comprised hypotonic children (n = 4). INTERVENTIONS Laryngotracheal reconstruction.

MAIN OUTCOMES AND MEASURES

The number of procedures performed after LTR to optimize the airway and whether the child was successfully decannulated.

RESULTS

All 16 of the neurologically intact patients (100%) were decannulated. Among children with a neurologic deficit, 5 of 7 (71%) were ultimately decannulated. No hypotonic children 0 of 4 were decannulated. The difference in rates of decannulation between unaffected and normotonic children with a neurologic deficit was not statistically significant (P = .08). However, the difference in outcomes between hypotonic children and neurologically intact patients was statistically significant (P  .001).

CONCLUSIONS AND RELEVANCE

Findings from this study suggest that hypotonic children may experience poorer rates of post-LTR decannulation compared with children without neurologic deficit. Dynamic upper airway obstruction may be unappreciated in hypotonic children. Future research may be directed at the appropriate evaluation and treatment of children with poor muscle tone and subglottic stenosis.