Integrated demultiplexing and amplification of coherent optical combs.

The explosive growth of the internet during the last few decades has been enabled by two complementary innovations in optical communications: the use of multiple optical channels within a single optical fibre, and the increase in the bandwidth of individual channels to hundreds of Gbps. Further increases in overall bandwidth look to be provided by more spectrally efficient optical superchannels that use coherent sub-carriers generated using optical orthogonal frequency division multiplexing (OFDM). Yet, a cost effective way of generating these signals has not been demonstrated. One crucial, but missing piece is an effective means to separate the closely frequency spaced optical sub-carriers from the coherent optical comb before placing information on each sub-carrier, and thus creating the OFDM signal. Here, we demonstrate a flexible strategy implemented in a compact photonic integrated circuit (PIC) that is used to separate and amplify these sub-carriers using on-chip injection locking.

Monolithically integrated low linewidth comb source using gain switched slotted Fabry-Perot lasers.

A monolithically integrated low linewidth optical comb is demonstrated by gain switching of a three-section laser device. The device consists of a slave and master section separated by a shared slotted mirror section. Wavelength tunability has been demonstrated by varying the electrical bias of each section. The number of comb lines is shown to almost double with the addition of optical injection from the master section into the slave. The unmodulated device has a full width half max linewidth of ∼ 500 kHz, while the comb line set were measured to be ∼ 600 kHz, with little degradation as a result of gain switching. The FSR (free spectral range) of the demonstrated comb is 4 GHz, which is tunable within the bandwidth of the device, with a central wavelength of 1580.3 nm.

Dense WDM transmission at 2 µm enabled by an arrayed waveguide grating.

We show, for the first time, dense WDM (8×20 Gbit/s) transmission at 2 µm enabled by advanced modulation formats (4-ASK Fast-OFDM) and the development of key components, including a new arrayed waveguide grating (AWGr) at 2 µm. The AWGr shows -12.8±1.78 dB of excess loss with an 18-dB extinction ratio and a thermal tunability of 0.108 nm/°C.

On-chip optical phase locking of single growth monolithically integrated Slotted Fabry Perot lasers.

This work investigates the optical phase locking performance of Slotted Fabry Perot (SFP) lasers and develops an integrated variable phase locked system on chip for the first time to our knowledge using these lasers. Stable phase locking is demonstrated between two SFP lasers coupled on chip via a variable gain waveguide section. The two lasers are biased differently, one just above the threshold current of the device with the other at three times this value. The coupling between the lasers can be controlled using the variable gain section which can act as a variable optical attenuator or amplifier depending on bias. Using this, the width of the stable phase locking region on chip is shown to be variable.

Echocardiographic Pulmonary Hypertension Predicts Post-transplantation Renal Allograft Failure.

BACKGROUND: Pulmonary hypertension in the setting of renal transplantation has been associated with early allograft dysfunction and increased mortality, but this relationship has not been extensively studied. METHODS: We performed a retrospective cohort study of adult patients who underwent their first renal transplantation in the years 2003-2009 and had pre-transplantation echocardiograms. Pulmonary hypertension was defined as right ventricular systolic pressure ≥40 mm Hg in the absence of left-sided valvular disease and/or left ventricular ejection fraction ≤50%. Eighty-two of 205 patients (40%) met the inclusion criteria. The relationship between pulmonary hypertension and death-censored allograft failure (hemodialysis dependence or retransplantation) and serum creatinine was assessed with the use of Cox hazard regression and generalized mixed models. RESULTS: The presence of pulmonary hypertension was associated with a 3-fold increase in the risk of death-censored allograft failure (95% confidence interval, 1.20-7.32; P = .02). Failure rates were 19% at 24 months and 51% at 96 months for those with pulmonary hypertension versus 7% at 24 months and 20% at 86 months for those without pulmonary hypertension (P = .01). Among those without graft failure, there was an increase in creatinine levels after transplantation (P = .01). Effect estimates were unchanged by adjustment for multiple covariates and when pulmonary hypertension was defined as right ventricular systolic pressure ≥36 mm Hg. CONCLUSIONS: Pulmonary hypertension before renal transplantation carries a 3-fold increased risk of death-censored allograft failure. The relationship between the pulmonary circulation and renal allograft failure warrants further study.

Cell mediated immunity (CMI) and post transplant viral infections--role of a functional immune assay to titrate immunosuppression.

Cell mediated immunity (CMI) was assessed by the ImmuKnow assay in 12 patients after kidney transplantation, who presented with viral infection. Treatment included lowering of immunosuppression in all cases and antiviral treatment if indicated. The assay was repeated during the follow up. The ImmuKnow assay at time of presentation of viral infections was 56.8+/-58.2 (range 3-178; median 22) ATP ng/ml. With the clearance of viral infection and lowering of immunosuppression, the assay showed an increase in the level of CMI at 194.5+/-118.9 (range 53-409; median 150) ATP ng/ml. There was viral clearance or stabilization in all cases and there was no incidence of allograft rejection. The ImmuKnow assay of CMI can be used to titrate initial immunosuppression reduction and its subsequent increase, in patients with viral infection after transplantation.

Excess risk of renal allograft loss and early mortality among elderly recipients is associated with poor exercise capacity.

BACKGROUND: Successful renal transplantation in the elderly offers substantial benefits in quality and life expectancy. However, in this group of patients there is an early increased risk of death compared with those remaining on dialysis. MATERIALS AND METHODS: Graft and patient outcomes in 64 older transplant recipients were compared with 338 patients aged 18 - 59 years. We identified potential risk factors that may predict clinical outcomes in older transplant recipients. A log-rank test and Cox regression analyses were performed to assess the impact of various patient characteristics on graft and patient survival. RESULTS: Among older patients, graft survival was 76.6% and 67% at 1 and 3 years, respectively. When graft survival was censored for death with functioning graft, the 1- and 3-year graft survival was 83% and 82%, respectively. Patient survival was 78% and 71% at 1 and 3 years, respectively. These survival rates were significantly lower than those of younger recipients. Pretransplant inactivity, delayed graft function, smoking history and longer waiting time predicted poor graft and patient survival. A history of chronic obstructive pulmonary disease, and peripheral vascular disease also predicted a higher mortality among older recipients. CONCLUSION: Older kidney transplant recipients are at high risk for allograft failure and early death. Poor functional capacity predicts a poor outcome for older patients undergoing renal transplantation. Therefore, careful patient selection is paramount, and every effort should be made to initiate timely interventions aimed at increasing physical activity in those with low fitness level.

Cryptosporidium infection in renal transplant patients.

Cryptosporidium parvum, an intracellular protozoan parasite, is a significant cause of gastrointestinal disease worldwide. Transmission can occur from an infected person, animal or fecally contaminated environment. The clinical manifestations of cryptosporidiosis are dependent on the immunologic state of the host. Infection among immunocompetent hosts results in diarrhea that is typically self-limited. In immunocompromised hosts, however, the infection may be protracted and life-threatening with no reliable antimicrobial therapy. In transplant patients, a course of antimicrobial therapy along with concurrent reduction in immunosuppression optimize immunologic status and may potentially lead to resolution of the infection.

Experience with sirolimus for calcineurin minimization/elimination in pancreas-after-kidney transplantation.

Pancreas after kidney (PAK) transplantation, associated with a persistent elevation in serum creatinine (defined as a >25% increase from baseline), was seen in 7 of 11 (64%) cases maintained on immunosuppressive therapy consisting of tacrolimus, mycophenolate mofetil, and prednisone. Patients were converted to sirolimus as a means of minimizing or eliminating exposure to tacrolimus, the presumed nephrotoxic agent. With the use of sirolimus-based immunosuppression, and with elimination or minimization of tacrolimus, renal function, as measured by serum creatinine, stabilized or improved in all cases.

Factors contributing to acute rejection in renal transplantation: the role of noncompliance.

Early episodes of acute rejection after renal transplantation reflect inadequate immunosuppression at a time of heightened immune challenge. Late acute rejection episodes, however, are less likely related to inadequacy of immunosuppression and may be due to patient noncompliance or overzealous weaning of immunosuppression. We evaluated 443 consecutive renal transplant recipients to determine the incidence and etiology of acute rejection. All episodes were confirmed by ultrasound-guided biopsy. The cause of each acute rejection was determined by chart review. Medication compliance was determined by history at the time of admission for biopsy. Over a follow-up period of 42 +/- 22 months, 87 patients (20%) suffered acute rejection. There was a trend toward fewer episodes of acute rejection with thymoglobulin induction and tacrolimus-based immunosuppression. Younger recipients had an increased risk of acute rejection (odds ratio 0.47, range 0.24-0.91, P = .027). Patient noncompliance with immunosuppression was associated with late acute rejection (P = .0002). Acute rejection increased the risk of allograft failure (P < .0001). Modifiable factors, including the choice of immunosuppression, reduce the risk of acute rejection. More importantly, the transplant recipient plays a substantial role in the maintenance of their allograft health through compliance with immunosuppressive drug therapy. Future strategies to improve compliance, including increased vigilance in high-risk patient groups, frequent medication review, and laboratory testing, should be encouraged.

Small bowel allograft rejection detected by serum intestinal fatty acid-binding protein is reversible.

We hypothesized that, following experimental small bowel transplantation, immunosuppressive therapy initiated on the day of the initial rise in serum intestinal fatty acid-binding protein (I-FABP) would result in graft salvage. In previously published work, we showed that I-FABP was not detectable in the serum of isografted Lewis rats, but could be measured in the peripheral circulation during small bowel allograft rejection. A clinically useful method to monitor trans- planted allografts for rejection should detect the problem early in its evolution so that treatment to reverse the process would salvage a functional organ. Lewis rats served as recipients of LBNF1 out-of-continuity small bowel allografts and were studied in two groups: group I (control) received no immunosuppression and group II received cyclosporine (CsA, 15 mg/kg/d, p.o.) when I-FABP rose to > or = 80 ng/ml. Serum I-FABP was measured daily until the time of sacrifice. Full-thickness graft biopsies were obtained on postoperative days 3 (baseline), 6 or 7 (elevated I-FABP), 10, and 14 (sacrifice). Following transplantation baseline serum I-FABP (day 2 or 3) averaged < or = 10.0 ng/ml. I-FABP remained at baseline through day 5 (range 0-50 ng/ml) in all animals and then rose abruptly on either day 6 or 7 (range 86-150 ng/ml; P < 0.001 vs. baseline). Histology on day 6 or 7 revealed a mild-to-moderate cellular rejection. Cyclosporine therapy reversed the rejection reaction and restored the bowel to normal histology. Serum I-FABP returned to baseline. In untreated animals, serum I-FABP remained elevated for several days and then returned to baseline levels coincident with fulminant rejection and mucosal sloughing. I-FABP was released into the peripheral circulation early in the evolution of acute rejection in this model of small bowel transplantation. Immunosuppressive therapy initiated when elevated levels of I-FABP were detected in the serum resulted in graft salvage. Cyclosporine immunotherapy consistently reversed rejection in this model. This article represents the first report of salvage of small bowel allografts when immunosuppressive therapy was instituted prospectively on the basis of a serum marker. Immunoreactive I-FABP appears to hold significant potential as a biochemical screening tool for acute rejection occurring In small bowell allografts.

Correlation of clinical outcomes after tacrolimus conversion for resistant kidney rejection or cyclosporine toxicity with pathologic staging by the Banff criteria.

BACKGROUND: Refractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal allograft loss. Previous studies demonstrated that 70-85% of the episodes of refractory acute rejection (AR) occurring in renal allograft recipients on a CsA-based immunosuppressive regimen could be salvaged by conversion to tacrolimus. No data are available regarding the correlation between allograft histology at the time of conversion and the response to tacrolimus. We examined the response to tacrolimus conversion in relation to preconversion biopsies stratified by the Banff criteria. METHODS: Since May 1992, we have converted 22 patients from CsA to tacrolimus as part of a rescue protocol. We report on 18 patients in whom 6-month follow-up was available after conversion for biopsy-proven AR (n=13) or CsA toxicity (n=5). Sixteen patients were recipients of renal allografts, including three second transplants, and two were recipients of kidney-pancreas transplants. All patients with AR were treated with one or more courses of methylprednisolone and OKT3 before conversion. Renal allograft biopsies were interpreted by a transplant pathologist blinded to the clinical history, and graded according to the Banff criteria. Responses to tacrolimus were scored as improved (creatinine returned to within 150% of baseline), stabilized (creatinine rise arrested), or failed (returned to dialysis). RESULTS; Mean follow-up was 17.3+/-8 months. Fourteen of 18 patients (78%) showed improvement or stabilization in renal function as assessed by creatinine at 6 months or 1 year (when available). Of the 13 patients with histological AR, nine (69%) improved, including five of six with borderline AR, two of three with grade I AR, and two of four with grade II AR. Of the four other patients with AR, two stabilized and two failed. Three of five patients with severe clinical rejection requiring dialysis (range 2-16 weeks) recovered renal function after conversion. Of five patients with CsA toxicity, two (40%) improved. Seven of eight patients who were converted to tacrolimus less than 90 days after transplantation improved, compared with only 4 of 10 who were converted more than 90 days after transplantation. No grafts were lost in patients with a creatinine <3.0 mg/dl at the time of conversion versus two of seven grafts lost when the creatinine was 3.1-5.0 mg/dl and two of eight grafts lost when the creatinine was >5.0 mg/dl. CONCLUSION: The majority of steroid and antilymphocyte antibody (OKT3 or ATGAM) unresponsive rejections in patients on CsA-based immunosuppression will improve or stabilize after conversion to tacrolimus. There was no correlation with allograft histology stratified by the Banff criteria and the response to tacrolimus. Although there was a trend toward a poorer response with more severe histological rejection, higher serum creatinine at the time of conversion, and longer time from transplantation to conversion, favorable responses were noted in all groups. This indicates that a trial of conversion is warranted, irrespective of the histological severity of injury.

Sump syndrome complicating Roux-en-Y hepaticojejunostomy: case report and review of the literature.

Sump syndrome is a rare complication of biliary-enteric anastomosis. Classically, the distal bile duct becomes obstructed by gastrointestinal debris after choledochoduodenostomy, resulting in cholangitis or, less commonly pancreatitis. Obstruction of the biliary tree by gastrointestinal contents after Roux-en-Y choledochojejunostomy or hepaticojejunostomy has not been described in the English-language literature. This report details the diagnostic and operative management of the first patient with sump syndrome after hepaticojejunostomy. The presumed pathophysiology was reflux of vegetable matter up the efferent limb, resulting in hepatic duct obstruction and cholangitis. The patient ultimately required complex choledochoscopic drainage of the intrahepatic biliary tree and revision of the previous Roux-en-Y hepaticojejunostomy.

Peripheral vascular disease after kidney-pancreas transplantation in diabetic patients with end-stage renal disease.

OBJECTIVE: To determine the long-term effect of a functioning pancreas transplant on peripheral vasculopathy. DESIGN: We compared the progression of peripheral vascular disease in 39 recipients of successful kidney-pancreas transplants (KPT) with 65 consecutive diabetic patients who received cadaver kidney transplants alone (KTA) during the same period in a nonrandomized, retrospective control study. The mean duration of follow-up was more than 4 years in both groups. SETTING: Academic subspecialty referral practice. PATIENTS: A consecutive sample of all KPT recipients with more than 6 months of pancreas allograft function performed between May 1, 1988, and April 30, 1995. All patients who received cadaver renal transplants for diabetic nephropathy during the same period and who maintained a functioning renal allograft for more than 6 months were included as controls. INTERVENTION: Kidney-pancreas transplantation. MAIN OUTCOME MEASURE: Progression of peripheral vascular complications (PVC) defined as any midfoot or limb amputation (AMP), any ischemic ulceration requiring treatment (ULCER), and lower-extremity bypass surgery or angioplasty (LEBP). Ulcers leading to amputation were considered as single events (AMP only). RESULTS: Thirty-five (90%) of 39 KPT recipients are insulin-free. The KTA recipients had more atherosclerotic risk factors, including a higher incidence of coronary artery disease (P = .008), higher serum cholesterol levels (P = .03), and higher triglyceride levels (P = .04) than KPT recipients. Peripheral vascular complications before transplantation were comparable (P = .94) between groups. After transplantation, there were 35 new PVC (9 AMP, 11 ulcers, and 15 LEBP) in 18 of 39 KPT recipients vs 32 PVC (10 AMP, 8 ulcers, and 14 LEBP) in 20 of 65 KTA recipients (P = .005), indicating that KPT recipients had more PVC than did KTA recipients, despite a functioning pancreas. Seven bypass grafts failed after KPT, resulting in 6 limb amputations. In contrast, only 3 limb amputations were performed in 14 patients undergoing lower-extremity bypass procedures after KTA. CONCLUSIONS: Despite fewer risk factors for peripheral vasculopathy and the presence of insulin independence, KPT recipients had a higher incidence of PVC than a cohort of uremic diabetic patients undergoing KTA during the same period. These data show that a functioning pancreas allograft performed with a renal transplantation not only does not alter the progression of peripheral vascular disease in patients with renal failure secondary to diabetic nephropathy but also may accelerate PVC.

Keeping up with the Jones's: open donor nephrectomy in the laparoscopic era.

Several new approaches have been developed to perform donor nephrectomy. These include laparoscopic donor nephrectomy and open donor nephrectomy performed through small incisions, herein referred to as "mini-open donor nephrectomy". In the past, we performed open donor nephrectomy via a standard flank incision. In October 2002, we introduced mini-open donor nephrectomy via an anterior, retroperitoneal approach. Contemporaneously, we offered the option of laparoscopic donor nephrectomy. Herein, we review our single-center experience with these three techniques. Mini-open donor nephrectomy was comparable to the laparoscopic approach for duration of narcotic requirement and donor length of stay. The laparoscopic procedure was more expensive. Both procedures demonstrated improvement over the flank approach by eliminating the risk of pneumothorax, neuropathy, and flank bulge. In addition, length of stay and narcotic requirements were higher with the flank approach. Mini-open donor nephrectomy provides a good alternative to laparoscopic surgery, offering the donor an equivalent convalescence at lower cost and potentially with reduced morbidity.

Segmental Renal Ischemia following Transplantation of Horseshoe Kidney as Separate Allografts.

Introduction. Horseshoe kidney is a congenital anomaly that presents unique challenges for the transplant surgeon. The mere presence of horseshoe kidney should not preclude consideration for transplantation. Case Report. A 33-year-old women suffering from end-stage renal disease underwent deceased donor renal transplant with a divided horseshoe kidney. We present a postoperative complication and the technical strategy for transplant salvage. The patient currently has excellent graft function. Discussion. Horseshoe kidneys do present challenges for successful transplantation. Though case reports of successful transplantation are increasing, we present a technical complication and successful transplant salvage strategy. Technical descriptions in the literature of successful back-table preparation strategies should help more transplant surgeons to begin to utilize this resource. Conclusion. This study concludes that horseshoe kidneys can be successfully used for transplantation and provides a technical strategy to salvage the transplant after a unique complication associated with these donor kidneys.