Endoscopic Duodenal–Jejunal Bypass Liner Rapidly Improves Type 2 Diabetes

Background

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal–jejunal bypass liner (DJBL).

Methods

Seventeen obese patients (BMI 30–50 kg/m²) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA_1c and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment.

Results

At 24 weeks after implantation, patients had lost 12.7?±?1.3 kg (p?<?0.01), while HbA_1c had improved from 8.4?±?0.2 to 7.0?±?0.2 % (p?<?0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6?±?0.5 vs. 9.0?±?0.5 vs. 8.6?±?0.5 mmol/L and 1,999?±?85 vs. 1,536?±?51 vs. 1,538?±?72 mmol/L/min, both p?<?0.01). In parallel, the glucagon response decreased (23,762?±?4,732 vs. 15,989?±?3,193 vs. 13,1207?±?1,946 pg/mL/min, p?<?0.05) and the GLP-1 response increased (4,440?±?249 vs. 6,407?±?480 vs. 6,008?±?429 pmol/L/min, p?<?0.01). The GIP response was decreased at week 24 (baseline—115,272?±?10,971 vs. week 24—88,499?±?10,971 pg/mL/min, p?<?0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation.

Conclusions

The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones.     

Cerebral cortical oxygenation: a pilot study

BACKGROUND: Cerebral hypoxia (cerebral cortical oxygenation [Pbro2] < 20 mm Hg) monitored by direct measurement has been shown in animal and small clinical studies to be associated with poor outcome. We present our preliminary results observing Pbro2 in patients with traumatic brain injury (TBI). METHODS: A prospective observational cohort study was performed. Institutional review board approval was obtained. All patients with TBI who required measurement of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbro2 because of a Glasgow Coma Scale score < 8 were enrolled. Data sets (ICP, CPP, Pbro2, positive end-expiratory pressure (PEEP), Pao2, and Paco2) were recorded during routine manipulation. Episodes of cerebral hypoxia were compared with episodes without. Results are displayed as mean +/- SEM; t test, chi2, and Fisher's exact test were used to answer questions of interest. RESULTS: One hundred eighty-one data sets were abstracted from 20 patients. Thirty-five episodes of regional cerebral hypoxia were identified in 14 patients. Compared with episodes of acceptable cerebral oxygenation, episodes of cerebral hypoxia were noted to be associated with a significantly lower mean Pao2 (144 +/- 14 vs. 165 +/- 8; p < 0.01) and higher mean PEEP (8.8 +/- 0.7 vs. 7.1 +/- 0.3; p < 0.01). Mean ICP and CPP measurements were similar between groups. In a univariate analysis, cerebral hypoxic episodes were associated with Pao2 < or = 100 mm Hg (p < 0.01) and PEEP > 5 cm H2O (p < 0.01), but not ICP > 20 mm Hg, CPP < or = 65 mm Hg, or Pac2 < or = 35 mm Hg. CONCLUSION: Cerebral oxymetry is confirmed safe in the patient with multiple injuries with TBI. Occult cerebral hypoxia is present in the traumatic brain injured patient despite normal traditional measurements of cerebral perfusion. Further research is necessary to determine whether management protocols aimed at the prevention of cerebral cortical hypoxia will affect outcome.     

Risk of End‐Stage Renal Disease Among Liver Transplant Recipients With Pretransplant Renal Dysfunction

Guidelines recommend restricting simultaneous liver–kidney (SLK) transplant to candidates with prolonged dialysis or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² for 90 days. However, few studies exist to support the latter recommendation. Using Scientific Registry of Transplant Recipients and Medicare dialysis data, we assembled a cohort of 4997 liver transplant recipients from February 27, 2002–January 1, 2008. Serial eGFRs were calculated from serum creatinines submitted with MELD reports. We categorized recipients by eGFR patterns in the 90 days pretransplant: Group 1 (eGFR always >30), Group 2 (eGFR fluctuated), Group 3 (eGFR always <30) and Group 4 (short‐term dialysis). For Group 2, we characterized fluctuations in renal function using time‐weighted mean eGFR. Among liver‐alone recipients in Group 3, the rate of end‐stage renal disease (ESRD) by 3 years was 31%, versus <10% for other groups (p < 0.001). In multivariable Cox regression, eGFR Group, diabetes (HR 2.65, p < 0.001) and black race (HR 1.83, p = 0.02) were associated with ESRD. Among liver‐alone recipients in Group 2, only diabetics with time‐weighted mean eGFR <30 had a substantial ESRD risk (25.6%). In summary, among liver transplant candidates not on prolonged dialysis, SLK should be considered for those whose eGFR is always <30 and diabetic candidates whose weighted mean eGFR is <30 for 90 days.     

Human CD4+CD25+ Regulatory T Cells Suppress Anti-Porcine Xenogeneic Responses

Due to the shortage of human organs, xenotransplantation is being explored as an alternative to allotransplantation, but immune rejection remains a major hurdle to its implementation. We tested the ability of human CD4+CD25+ T cells (Treg cells) to suppress CD4+ T cell-mediated anti-porcine xenoresponses usingin vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and suppressed the proliferative response of CD4+CD25- T cells in a dose-dependent manner, and comparison of the allo- and xenoresponses indicated that more Treg cells might be required to suppress the xenogeneic response than the allogeneic response. Stimulation of CD4+CD25- T cells with porcine cells resulted in secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells suppressed the secretion of these cytokines, as well as the CD4+CD25- T-cell cytolytic response against porcine cells. These results suggest a potential role for Treg cells in promoting xenograft survival.     

Orthotopic liver transplantation with vena cava preservation in cirrhotic patients: is systematic temporary portacaval anastomosis a justified procedure?

INTRODUCTION: We evaluated the peri- and postoperative effects of the lack of a temporary portocaval anastomosis (TPCA) during orthotopic liver transplantation (OLT) in 84 patients with cirrhosis. PATIENTS AND METHODS: From December 1996 to December 2002, 156 liver transplant recipients included (54%; 60 men and 24 women) of mean age 52 +/- 9 years with portal hypertension. In whom peri- and postoperative data were analyzed. RESULTS: The median fall in mean arterial pressure upon vascular clamping and unclampings was 20 mm Hg (range 15 to 75), while the median duration of portal vein clamping was 77 minutes. The median amount of blood autotransfusion was 1100 mL (range 0 to 5400). The median number of red blood cell and fresh-frozen plasma units transfused were 5 and 6.5, respectively. The median intraoperative urinary output was 72 mL/h (range 11 to 221). Three patients (3.5%) presented a perioperative complication, but no perioperative death was observed. Six patients experienced an early postoperative complication (<10 days): five hemodynamic complications and one transient renal failure, which did not require hemodialysis. One patient (1%) died at 12 hours after OLT from acute pulmonary edema. CONCLUSION: This study shows that systematic TPCA during OLT with preservation of the native retrohepatic vena cava in cirrhotic patients does not appear to be justified. In contrast, peri- and postoperative hemodynamic parameters as well as blood component requirements were comparable to those of the literature reporting OLT with straightforward TPCA.     

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.     

Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring

OBJECT: An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is recommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the treatment of TBI was associated with an improved patient outcome. METHODS: Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had been admitted to a Level I trauma center were evaluated as part of a prospective observational database. Patients treated with ICP and brain tissue PO2 monitoring were compared with historical controls matched for age, pathological features, admission GCS score, and Injury Severity Score who had undergone ICP monitoring alone. Therapy in both patient groups was aimed at maintaining an ICP less than 20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2 was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty-five patients with a mean age of 44 +/- 14 years were treated using an ICP monitor alone. Twenty-eight patients with a mean age of 38 +/- 18 years underwent brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in each group. The mortality rate in patients treated using conventional ICP and CPP management was 44%. Patients who also underwent brain tissue PO2 monitoring had a significantly reduced mortality rate of 25% (p < 0.05). CONCLUSIONS: The use of both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2 is associated with reduced patient death following severe TBI.     

Complications Related to Dapsone Use for Pneumocystis Jirovecii Pneumonia Prophylaxis in Solid Organ Transplant Recipients

Dapsone, used for prevention of Pneumocystis jirovecii infections, has been reported to cause hemolytic anemia and methemoglobinemia; its tolerability in solid organ transplant recipients is not well described. We investigated dapsone-related adverse events in patients undergoing solid organ transplantation from 1999 to 2004. Transplant providers identified patients for the investigators who then reviewed the patients' hospital and outpatient records. Sixteen solid organ transplant recipients fit case definitions for dapsone-related hemolytic anemia (n = 11) or methemoglobinemia (n = 5). Median time from event to dapsone discontinuation was 15 days; all patients improved after drug discontinuation. G6PD enzyme activity was normal in all patients whose test results were available. Dapsone may be associated with hemolytic anemia or methemoglobinemia, even with normal G6PD levels. These events are often not promptly recognized, and drug discontinuation is delayed. Dapsone-related hemolytic anemia or methemoglobinemia should be considered in solid organ transplant recipients with unexplained anemia or hypoxia.     

Laparoscopic drainage of postappendectomy- retained fecalith and intra-abdominal abscess in the pediatric population

Retained fecalith after an appendectomy is an uncommon complication frequently associated with intra-abdominal abscess. Treatment options include percutaneous, open, or laparoscopic drainage of the abscess and retrieval of the fecalith, as antibiotics and drainage alone are usually insufficient. Laparoscopy offers the advantages of enhanced visualization of the abdomen, improved cosmesis, and a quicker return to normal daily activities. The principles of laparoscopic treatment include the careful identification of all anatomic landmarks, as the abscesses are frequently adherent to intra-abdominal structures compromising the safety of the operation. In this paper, we present 2 cases of laparoscopic drainage of an intra-abdominal abscess with retrieval of a fecalith in pediatric patients 1 and 6 weeks after an initial appendectomy and a review the literature.