Farokh Demehri - Academia.edu (original) (raw)

Papers by Farokh Demehri

Journal of Intensive Care Medicine, 2014

Gallstone-related disease is among the most common clinical problems encountered worldwide. The m... more Gallstone-related disease is among the most common clinical problems encountered worldwide. The manifestations of cholelithiasis vary greatly, ranging from mild biliary colic to life-threatening gallstone pancreatitis and cholangitis. The vast majority of gallstone-related diseases encountered in an acute setting can be categorized as biliary colic, cholecystitis, choledocholithiasis, and pancreatitis, although these diagnoses can overlap. The management of these diseases is uniquely multidisciplinary, involving many specialties and treatment options. Thus, care may be compromised due to redundant tests, treatment delays, or inconsistent management. This review outlines the evidence for initial evaluation, diagnostic workup, and treatment for the most common gallstone-related emergencies. Key principles include initial risk stratification of patients to aid in triage and timing of interventions, early initiation of appropriate antibiotics for patients with evidence of cholecystitis or cholangitis, patient selection for endoscopic biliary decompression, and growing evidence in favor of early laparoscopic cholecystectomy for clinically stable patients.

Current Opinion in Clinical Nutrition and Metabolic Care, 2015

To review the benefits of enteral nutrition in contrast to the inflammatory consequences of admin... more To review the benefits of enteral nutrition in contrast to the inflammatory consequences of administration of parenteral nutrition and enteral deprivation. To present the most recent evidence for the mechanisms of these immunologic changes and discuss potential areas for modification to decrease infectious complications of its administration. There is significant data supporting the early initiation of enteral nutrition in both medical and surgical patients unable to meet their caloric goals via oral intake alone. Despite the preference for enteral nutrition, some patients are unable to utilize their gut for nutritious gain and therefore require parenteral nutrition administration, along with its infectious complications. The mechanisms behind these complications are multifactorial and have yet to be fully elucidated. Recent study utilizing both animal and human models has provided further information regarding parenteral nutrition&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s deleterious effect on intestinal epithelial barrier function along with the complications associated with enterocyte deprivation. Changes associated with parenteral nutrition administration and enteral deprivation are complex with multiple potential areas for modification to allow for safer administration. Recent discovery of the mechanisms behind these changes present exciting areas for future study as to make parenteral nutrition administration in the enterally deprived patient safer.

Surgery, Jan 22, 2015

Distraction enterogenesis may provide a novel therapy for short bowel syndrome. Previously descri... more Distraction enterogenesis may provide a novel therapy for short bowel syndrome. Previously described methods have relied on isolated intestinal segments or transmural fixation because of ineffective endoluminal attachment. We hypothesized that a novel approach of geometric coupling between a tapering device and the mesenteric curvature would allow trans-stomal distraction enterogenesis. A catheter device was designed with tapering stiffness, consisting of a stiff catheter with a taper to a flexible latex tip to prevent perforation. Yorkshire pigs underwent creation of a jejunal Roux limb with device placed via jejunostomy. Intestinal attachment was achieved without a substantial decrease in bowel perfusion as measured by laser Doppler. An external clamp was secured at the stoma to provide external fixation of the device. The catheter was advanced 1 cm/day for either 7 or 14 days before explant. After 7 days, the distracted segment achieved a mean ± SD increase in length of 37 ± 6% v...

Journal of Pediatric Surgery, 2015

The purpose of this study was to identify risk factors for the development of metabolic bone dise... more The purpose of this study was to identify risk factors for the development of metabolic bone disease (MBD) in pediatric intestinal failure (IF). A retrospective single-center study of 36 pediatric IF patients who were screened for MBD was performed. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Simple regression analysis was initially performed to screen predictors, followed by multivariate step-wise linear regression analysis to identify risk factors of MBD. Mean lumbar spine BMD Z-score was -1.16±1.32, and 50.0% of patients had a BMD Z-score less than -1.0. Deficiency of 25-hydroxyvitamin-D (25-OHD &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;30ng/ml) was present in the 63.8% of patients, while 25.0% had hyperparathyroidism (intact parathyroid hormone (PTH)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;55pg/ml). Seven patients (19.4%) had bone pain, of which 4 (11.1%) suffered a pathologic fracture. Using multivariate analysis, parenteral nutrition (PN) duration predicted decreased BMD (B=-0.132, p=0.006). Serum 25-OHD nonsignificantly correlated with BMD Z-score (B=0.024, p=0.092). Interestingly, repeat DXA after increasing vitamin D supplementation showed no improvement in BMD Z-score (-1.18±1.49 vs -1.36±1.47, p=0.199). Pediatric IF is associated with a significant risk of MBD, which is predicted by the duration of PN-dependence. These findings underscore the importance of BMD monitoring. Better therapies for treating IF-associated MBD are needed.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 17, 2015

Recent studies suggest a close interaction between epidermal growth factor (EGF) and TLR signalin... more Recent studies suggest a close interaction between epidermal growth factor (EGF) and TLR signaling in the modulation of intestinal epithelial cell (IEC) proliferation; however, how these signaling pathways adjust IEC proliferation is poorly understood. We utilized a model of total parenteral nutrition (TPN), or enteral nutrient deprivation, to study this interaction as TPN results in mucosal atrophy due to decreased IEC proliferation and increased apoptosis. We identified the novel finding of decreased mucosal atrophy in TLR4 knockout (TLR4KO) mice receiving TPN. We hypothesized that EGF signaling is preserved in TLR4KO-TPN mice and prevents mucosal atrophy. C57Bl/6 and strain-matched TLR4KO mice were provided either enteral feeding or TPN. IEC proliferation and apoptosis were measured. Cytokine and growth factor abundances were detected in both groups. To examine interdependence of these pathways, ErbB1 pharmacologic blockade was used. The marked decline in IEC proliferation with T...

Surgery, 2015

To investigate the effect of nutrient withdrawal on human intestinal epithelial barrier function ... more To investigate the effect of nutrient withdrawal on human intestinal epithelial barrier function (EBF). We hypothesized that unfed mucosa results in decreased EBF. This was tested in a series of surgical small intestinal resection specimens. Small bowel specifically excluding inflamed tissue, was obtained from pediatric patients (aged 2 days to 19 years) undergoing intestinal resection. EBF was assessed in Ussing chambers for transepithelial resistance (TER) and passage of fluorescein isothiocyanate (FITC)-dextran (4 kD). Tight junction and adherence junction proteins were imaged with immunofluorescence staining. Expression of Toll-like receptors (TLR) and inflammatory cytokines were measured in loop ileostomy takedowns in a second group of patients. Because TER increased with patient age (P < .01), results were stratified into infant versus teenage groups. Fed bowel had significantly greater TER versus unfed bowel (P < .05) in both age populations. Loss of EBF was also observ...

Frontiers in cellular and infection microbiology, 2013

Total parenteral nutrition (TPN), a commonly used treatment for patients who cannot receive enter... more Total parenteral nutrition (TPN), a commonly used treatment for patients who cannot receive enteral nutrition, is associated with significant septic complications due in part to a loss of epithelial barrier function (EBF). While the underlying mechanisms of TPN-related epithelial changes are poorly understood, a mouse model of TPN-dependence has helped identify several contributing factors. Enteral deprivation leads to a shift in intestinal microbiota to predominantly Gram-negative Proteobacteria. This is associated with an increase in expression of proinflammatory cytokines within the mucosa, including interferon-γ and tumor necrosis factor-α. A concomitant loss of epithelial growth factors leads to a decrease in epithelial cell proliferation and increased apoptosis. The resulting loss of epithelial tight junction proteins contributes to EBF dysfunction. These mechanisms identify potential strategies of protecting against TPN-related complications, such as modification of luminal b...

Pediatric surgery international, 2014

Distraction enterogenesis may provide a novel therapy for short bowel syndrome (SBS). Previously ... more Distraction enterogenesis may provide a novel therapy for short bowel syndrome (SBS). Previously described methods have relied upon isolated intestinal segments or transmural fixation. Our objective was to develop a novel, fully endoluminal device, permitting placement and removal through an enteral stoma or orifice. A flexible device was designed consisting of two latex balloons mounted on coaxial catheters. The inner catheter allowed longitudinal force transmission from an external spring. Yorkshire pigs underwent jejunal Roux limb creation with device placement via jejunostomy. Balloons were inflated to 52 mmHg without significant reduction in bowel perfusion as measured by laser Doppler. The device was explanted after 7 days. Distracted bowel achieved an increase in length of 26.1 ± 6.1 % vs nondistracted fed bowel. As the device resided in unfed bowel, a 66.7 ± 14.5% increase vs unfed bowel was noted. These corresponded to a gain of 6.3 ± 2.3 cm (0.9 ± 0.3 cm/day) and 12.9 ± 7....

Journal of pediatric surgery, 2015

This study examined predictors of achieving enteral autonomy among pediatric short bowel syndrome... more This study examined predictors of achieving enteral autonomy among pediatric short bowel syndrome (SBS) patients remaining on parenteral nutrition (PN) beyond one year. A retrospective single-institution study of 171 pediatric SBS patients (defined as ≥50% small bowel (SB) loss or ≥60days of PN with onset before 6weeks of age) was performed. Multivariate Cox proportional hazards analysis was conducted, with subgroup analysis of patients on PN for ≥1year (n=59). Primary outcome was successful wean from PN. Over a follow-up of 4.1±4.8years, 64.3% of children weaned from PN. Mortality was 15.2%. Presence of ≥10% expected SB length (hazard ratio [HR] 6.48, p=0.002) or an ileocecal valve (ICV; HR, 2.86, p<0.001) predicted PN weaning. Of those on PN ≥1year, the wean rate was 50.8%, and ICV no longer predicted weaning (p=0.153). Predictors among those on PN ≥1year were: ≥10% expected SB length (HR, 8.27, p=0.010), intestinal atresia (HR, 4.26, p=0.011), and necrotizing enterocolitis (NE...

Pediatric Surgery International, 2013

Hirschsprung-associated enterocolitis (HAEC) is a common and sometimes life-threatening complicat... more Hirschsprung-associated enterocolitis (HAEC) is a common and sometimes life-threatening complication of Hirschsprung disease (HD). Presenting either before or after definitive surgery for HD, HAEC may manifest clinically as abdominal distension and explosive diarrhea, along with emesis, fever, lethargy, and even shock. The pathogenesis of HAEC, the subject of ongoing research, likely involves a complex interplay between a dysfunctional enteric nervous system, abnormal mucin production, insufficient immunoglobulin secretion, and unbalanced intestinal microflora. Early recognition of HAEC and preventative practices, such as rectal washouts following a pull-through, can lead to improved outcomes. Treatment strategies for acute HAEC include timely resuscitation, colonic decompression, and antibiotics. Recurrent or persistent HAEC requires evaluation for mechanical obstruction or residual aganglionosis, and may require surgical treatment with posterior myotomy/myectomy or redo pullthrough. This chapter describes the incidence, pathogenesis, treatment, and preventative strategies in management of HAEC.

Journal of Surgical Education, 2015

Busy surgical services with diverse team members and frequent handoffs create barriers to patient... more Busy surgical services with diverse team members and frequent handoffs create barriers to patient- and family-centered care. The aim of this study was to determine whether the use of cards containing team member names, roles, and photographs-&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Surgical Baseball Cards&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (SBCs)-would improve patient recognition of caregivers and whether this would improve patient satisfaction. A prospective, controlled study was performed of all adult patients admitted to 2 academic acute care general surgery services with alternating admitting days. Surgical team members on one service had SBCs to give patients at introduction, whereas the control service used no such tool. Before discharge, patients completed a survey consisting of a quiz requiring matching of caregiver photographs to names and roles (5-point maximum), questions rating select elements of patient satisfaction (5-point Likert scale), and an opportunity to provide comments. Department of Surgery, University of Michigan, Ann Arbor, MI, a university teaching hospital. A total of 162 patients were included over 2 months, with at least a 24-hour admission to an acute care general surgery service. Overall, 60% of patients in the intervention arm received SBCs. Per-unit SBC cost was 0.16 USD. Patients who received SBCs had significantly improved identification of team members based on name (1.7 ± 1.4 vs 1.2 ± 1.5, p = 0.02) and role (1.6 ± 1.4 vs 0.9 ± 1.2, p = 0.02) than controls did. All the SBC recipients and 88% of controls felt that SBCs should be implemented hospital-wide. SBC recipients reported a trend toward increased comfort with resident involvement in care (4.6 ± 0.7 vs 4.5 ± 0.9, p = 0.14). Among themes discerned from free-response comments, 46% of SBC recipients commented on the innovative nature of SBCs and 29% noted improved team identification. Overall, 17% of SBC recipients commented positively on patient-centered care (vs 3% of controls), whereas 5% commented negatively on patient-centered care (vs 15% of controls); 8% of SBC recipients commented positively on coordination of care (vs 1% of controls), whereas 5% commented negatively on coordination of care (vs 24% of controls). SBCs provide reasonable value by improving patient recognition of healthcare team members and understanding of team member roles, and they are associated with positive patient feedback regarding coordination of care and patient-centered care.