Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2).

BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).

Outcome of live and deceased donor renal transplantation in patients aged ≥55 years: A single-center experience.

Renal transplantation (RTx) has now become an accepted therapeutic modality of choice for elderly ESRD patients. This single-center study was undertaken to evaluate the outcome of RTx in ESRD patients ≥55 years. A total of 103 patients underwent RTx 79 living related living donors [LD], 24 deceased donors [DD]) at our center. Post-transplant immunosuppression consisted of calcineurin inhibitor-based regimen. The mean donor age was 58.3 years in the LD group and 59.5 years in the DD group. Male recipients constituted 92% in LD and 75% in DD group. In living donor renal transplantation, 1- and 5-year patient survival was 93% and 83.3% respectively and death-censored graft survival was 97.3% and 92.5% respectively. There were 12.6% biopsy proven acute rejection (BPAR) episodes and 12.6% patients were lost, mainly due to infections. In deceased donor renal transplantation, 1- and 5-year patient survival was 79.1% and 74.5% respectively and death-censored graft survival was 95.8% and 85.1% respectively. There were 12.5% BPAR episodes and 25% of patients were lost, mainly due to infections. RTx in ESRD (≥55 years) patients has acceptable patient and graft survival if found to have cardiac fitness and therefore should be encouraged.

Outcome of renal transplantation from deceased donors after cardiac death: a single-center experience from a developing country.

BACKGROUND: Limited information is available in the literature about the use of organs from donation after cardiac death (DCD) renal transplantation (RTx) from a developing country. MATERIAL AND METHODS: We report RTx outcome between DCD donors ≥70 years (Group 1; n = 14; mean age, 75.7 ± 5.81) and DCD donors <70 years (Group 2; n = l9; mean age, 51.7 ± 10.1) between January 1999 and January 2012. The mean age of recipients was 39.5 ± 14.7 years, 24 of whom were males. The mean donor age was 61.9 ± 14.6 years, 21 of whom were males. All recipients received single-dose thymoglobulin induction followed by immunosuppression with a steroid, a calcineurin inhibitor, and mycophenolate mofetil or azathioprine. Statistical analysis used chi-square test and unpaired Student t test. Kaplan-Meier curves were used for survival analysis. RESULTS: Over a mean follow-up of 3.21 ± 3.46 years, one-, five-, and ten-year, patient survival rates were 77%, 67.4%, and 67.4%, respectively, and death-censored graft survival rates were 85.7% for one, five, and ten years. Delayed graft function (DGF) was observed in 36.4% (n = 12) with 12.1% (n = 4) biopsy-proven acute rejection (BPAR). Patient survival (P = .27), graft survival (P = .20), DGF (P = .51), and BPAR (P = .74) were similar in 2 groups. A total of 27.2% (n = 9) of patients died, mainly due to infections (n = 5). CONCLUSION: Given the widespread organ shortage, outcomes of controlled DCD renal transplantation has a potential to expand the donor pool and shorten the waiting list for RTx, encouraging the use of this approach even in low-income countries.

Impact of anti-tobacco warning labels on behaviour of tobacco users in one of the cities of Gujarat, India.

BACKGROUND: Tobacco use continues to be the leading global cause of preventable deaths, killing nearly 6 million people worldwide each year. Tobacco control must be given the high priority by scaling up tobacco control measures. In India under Control of Tobacco Product Act, it is mandatory to keep the warning labels over all kind of tobacco products in order to minimise the use of tobacco. OBJECTIVES: Review of the knowledge regarding warning labels printed on tobacco products among its users and to evaluate the impact of them on addicting behaviour. METHODOLOGY: A Cross Sectional study was carried out among the group of people using tobacco in any form. Total 776 tobacco users were enrolled in the study. RESULTS: Mean age of tobacco user was 41.4 years. Out of total 776 tobacco users, 561 (72.3%) had ever noticed warning signals over the tobacco products. Among those who have noticed warning labels, 64.4 % became aware about health effects and 66% have thought to quit tobacco. Tobacco users of young age group (15-45) were more aware regarding warning labels. Females were less aware. As level of education increases number of tobacco users who tried to quit or reduced the daily quantity of tobacco intake were also increases. CONCLUSIONS: Positive impact of warning labels has been seen among the tobacco users who have noticed them. Not all the tobacco users were aware regarding the presence of warning labels as per the findings of present study.

World kidney day 2010: medical aspects of 10 live-donor renal transplantations in a single center from a developing country.

BACKGROUND: World Kidney Day (WKD) has become the most widely celebrated event associated with kidney disease in the world and the most successful effort to raise awareness among both the general public and government health officials about the dangers of kidney disease. We celebrated WKD 2010 in a unique way by performing 10 live-donor renal transplantations (RTx) on March 11, 2010. PATIENTS AND METHODS: We report a single-center experience on RTx vis-à-vis patient/graft survival, graft function in terms of serum creatinine (SCr) level, and rejection episodes in 10 live-donor RTx performed on WKD. Recipient diseases leading to end-stage renal disease (ESRD) were chronic glomerulonephritis (60%), benign nephrosclerosis (20%), and chronic interstitial nephritis (20%). Mean recipient age was 35 ± 8.7 years. Nine recipients were males. Mean donor age was 37 ± 8.7 years, Nine donors were females. Donors were spouse (n = 6), mother (n = 2), sister (n = 1), and extended family member (n = 1), with mean HLA match 1.8 ± 1.48. All patients received steroids, calcinueurin inhibitors, and mycophenolate mofetil/azathioprime for maintenance immunosuppression. RESULTS: During a mean follow-up time of 18 months, patient and graft survival rates were 90% and 90%, respectively, with a mean SCr level of 1.21 mg/dL; 20% had biopsy-proven acute rejection. One patient died due to infection after antirejection therapy. CONCLUSION: RTx has acceptable graft and patient survival. RTx is the best cost-effective therapeutic modality for patients suffering from ESRD and should be encouraged in view of organ shortage on events such as WKD. To our knowledge, this is the first report from a developing country on 10 successful RTx on WKD.

Carbon dioxide absorption during laparoscopic donor nephrectomy: a comparison between retroperitoneal and transperitoneal approaches.

AIM: Previous studies have suggested that retroperitoneal and transperitoneal approaches for laparoscopic donor nephrectomy are associated with variable carbon dioxide (CO(2)) absorption, which can cause significant morbidity. The approach that results in greater CO(2) absorption is a matter of debate. We studied patients undergoing transperitoneal/retroperitoneal donor nephrectomy to determine relative CO(2) absorption, incidence of subcutaneous emphysema, pneumothorax, and pneumomediastinum, seeking to establish a correlation between the incidence of subcutaneous emphysema and CO(2) elimination. MATERIALS AND METHODS: This was a prospective nonrandomized, single-center, two-arm clinical study of 60 kidney donors undergoing laparoscopic nephrectomy by transperitoneal (n = 30) or retroperitoneal (n = 30) approach. CO(2) elimination was calculated using end tidal CO(2), tidal volume, respiratory rate, and weight of the donor. We studied intraoperative CO(2) elimination and CO(2) retention-related morbidities. RESULTS: There was a significant increase in CO(2) elimination in the first 30 minutes of insufflation followed by a plateau for the remainder of procedure. There was no difference in CO(2) elimination in either procedure at any time interval. Patients with subcutaneous emphysema showed significantly greater CO(2) elimination, which decreased with desufflation. CONCLUSION: CO(2) absorption during laparoscopy did not depend on the route of surgery. Subcutaneous emphysema was strongly and independently associated with a greater degree of CO(2) absorption during laparoscopic surgery.

In pursuit of the ultimate: the initial Ahmedabad journey toward transplantation tolerance.

We designed a prospective clinical trial of 357 patients divided in two groups--treated (n = 201) and controls (n = 156)--to evaluate effects of donor hematopoietic stem cell transplantation (HSCT) with minimal nonmyeloablative conditioning for tolerance induction in living related donor renal allograft recipients. Conditioning included donor leukocyte infusions, target-specific irradiation, anti-T-cell antibody, cyclophosphamide, cyclosporine (CsA), followed by bone marrow (BM)-derived and peripheral blood stem cell (PBSC) infusion into thymus, liver, BM, and periphery, with mean total dose of 20 x 10(8) nucleated cells/kg body weight (BW) (mean CD34(+) count: 0.9%) pretransplantation. CsA (3 mg/kg BW/d) and prednisolone (10 mg/d) were used for immunosuppression. Azathioprine/mycophenolate mofetil were added in the event of an acute rejection episode. The controls underwent transplantation with three drug immunosuppression. With a mean follow-up of 21.5 months, the treated cohort showed better allograft function with mean serum creatinine (SCr), 1.42 +/- 0.31 mg% in contrast with the controls mean SCr, 1.61 +/- 0.52 mg% (P < .0001) at 23.9 months follow-up. One-year allograft/patient survival was 95%/96.7% versus 89%/93.4%, respectively. Peripheral blood chimerism by fluorescent in situ hybridization was 0.8% +/- 0.2% in the subset of treated patients with gender-mismatched donors. No graft-versus-host disease was noted. Nine patients with donor-specific cytotoxic alloantibodies pretransplantation showed a decrease in positivity to <15% post-HSCT and were transplanted safely. A transient rise in donor-specific cytotoxic alloantibodies was noted in 19 treated patients post-HSCT, 14 of whom returned to the transplantable range within 2 weeks and five required a desensitization protocol. "Prope" tolerance may be induced in living related donor renal transplantation across major histocompatability complex barriers using HSCT with minimal nonmyeloablative conditioning.

Successful generation of donor specific hematopoietic stem cell lines from co-cultured bone marrow with human embryonic stem cell line: a new methodology.

We report the generation of 30 healthy human embryonic stem cell (h-ESC) lines from 33 voluntary oocyte donors using a donor somatic cell nuclear transfer (SCNT) technique on 190 oocytes. Our aim was to coculture them with their own bone marrow (BM) to generate hematopoietic progenitor cells for therapeutic purposes. Pluripotency and undifferentiated stage were confirmed using molecular cell surface markers. Normal karyotype of these cell lines was confirmed. Here we demonstrate that SCNT-h-ESCs differentiate to hematopoietic precursors when cocultured with unmodified, nonirradiated donor BM. We did not use any xenogeneic material for this hematopoietic differentiation. Hematopoietic precursors derived from them expressed cell surface antigens CD45/34. When further cultured with hematopoietic growth factors these hematopoietic precursors formed characteristic myeloid, erythroid, and megakaryocyte lineages. Phenotypic CD34+ cells derived from NT-h-ESCs were functionally similar to their counterparts in primary hematopoietic tissues like BM, umbilical cord, and blood. More terminally differentiated hematopoietic cells derived from h-ESCs under these culture conditions also expressed normal surface antigens like glycophorin A on erythroid cells, CD15 on myeloid cells, and CD41 on megakaryocytes. We report generation of hematopoietic progenitor cells from h-ESC lines by a SCNT technique, with differentiation into further lineages with structural and functional similarities to their adult counterparts in vivo. This novel alternative source of CD34+ stem cells from h-ESC lines generated without any xenogeneic material might be used to create transplantation tolerance, to implement regenerative medicine, and to treat autoimmune disorders.

Hematopoietic stem cell transplantation in autoimmune diseases: the Ahmedabad experience.

INTRODUCTION: Autoimmune disease represents a (AD) breakdown of natural tolerance against autoreactive antigens leading to a high mortality and morbidity. The reaction is usually polyclonal; T- and B-cell components of the hematopoietic system are responsible for disease progression. Allogeneic/autologous hematopoietic stem cell transplantation (HSCT) are the current modalities for treating drug-resistant AD. PATIENTS AND METHODS: We present a single-center retrospective evaluation of allogeneic HSCT with nonmyeloablative, low-intensity conditioning in nine patients (five males, four females) with pemphigus vulgaris (PV) and 27 patients with systemic lupus erythematosus (SLE; 3 males, 24 females). The mean follow-up period was 4.24 years for PV and 4.9 years for SLE. Cytokine-mobilized HSC from unmatched related donors, with mean dose of 21.3 x 10(8) nucleated cells/kg body weight (BW; mean CD34(+) count, 6 x 10(6)/kg BW) was administered in to the thymus as well as the portal and peripheral circulations of recipients. Cyclosporine (4 +/- 1 mg/kg BW per day) and prednisolone (10 mg/kg BW per day) were administered for 6 months to protect mixed chimerism. A subset of patients with cross-gender donors were analyzed for peripheral blood chimerism at 1 month post-HSCT and every 3 months thereafter. RESULTS: Sustained clinical remission with peripheral lymphohematopoietic chimerism of 0.7 +/- 0.3% was observed in PV, whereas SLE relapsed after mean of 7.35 months of disease-free interval associated with fall in chimerism from 5 +/- 3% to < or =0.08 +/- 0.03%. CONCLUSION: HSCT was effective to achieve early clinical remission of PV; and in SLE relapsed after a 7.35-month disease-free interval accompanied by a fall in mixed lymphohematopoietic chimerism.

Impact of retroperitoneoscopic donor nephrectomy on renal allograft in Indian and African recipients.

AIM: To evaluate the impact of laparoscopic donor nephrectomy on renal allografts in Indian and African recipients. MATERIAL AND METHODS: Between September 2004 and August 2006, 125 retroperitoneoscopic donor nephrectomies were performed. Ninety-four donors were Indian (group A) and 32, African (group B). Three ports were used for left-sided and four for right-sided surgery, respectively. Hem-o-lok clips were used to control arteries and veins on left side and arteries on right side while an Endo-TA stapler was used on the right side to obtain an inferior vena caval cuff. RESULTS: The mean operative times in groups A and B were 130 and 134 minutes; mean blood loss, 100.4 mL and 85.3 mL; and mean warm ischemia time, 242.1 seconds and 234.5 seconds, respectively. Recipient mean serum creatinine value on day 7 was 1.9 and 1.6 mg%, and on day 28, 1.44 mg% and 1.4 mg%, respectively. CONCLUSION: Early adequate allograft function following retroperitoneoscopic donor nephrectomy was comparable in African and Indian patients, suggesting that no racial advantage was observed in this procedure.

Embryonic stem cell derived and adult hematopoietic stem cell transplantation for tolerance induction in a renal allograft recipient:--a case report.

UNLABELLED: We generated an human embryonic stem cell (hESC) line to augment chimerism-associated tolerance. A 40-year-old African with chronic glomerulonephritis-chronic renal failure with 100% G6PD enzyme deficiency presented for renal transplantation with a 27-year-old, 6/6 HLA-matched sister as a willing donor. METHOD: We generated an hESC line from the donor's oocytes using long ovarian stimulation protocol simultaneously with tolerance induction protocol. A nuclear transfer (NT)-hESC line was derived by transferring a donor cumulus cell into an enucleated oocyte, subjected to electrical fusion, and cultured for 5 days. ESCs hatched from the blastocyst on day 6 were cocultured with her unmodified bone marrow for 2 days and suspended in Ringer's lactate. Five milliliters of suspension were collected for cell counting, viability, pluripotency, flow cytometry, and karyotyping. The remaining suspension was infused into the periphery of the recipient. Transplantation was performed 1 week later following a negative lymphocytotoxicity cross-match test using no immunosuppression. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique. Allograft biopsy was performed on day 7. RESULTS: NT-hESC CD34+ count was 7.6%, viability 100%, karyotyping normal, pluripotency markers: SSEA-1, SSEA-4, OCT-3/4, TRA-1/60:positive; 12% PBC was noted at 1 week after transplantation. Serum creatinine was 1.2 mg%, graft biopsy was unremarkable, and G6PD enzyme deficiency was corrected to 0% at 100 days posttransplant. Liver function tests and hematology profile were unremarkable for graft-versus-host disease. CONCLUSION: This is the first report of tolerance induction using NT-hESC-induced hematopoietic chimerism with synergistic use of adult bone marrow. It was safe and effective.

Allogeneic hematopoietic stem-cell transplantation, mixed chimerism, and tolerance in living related donor renal allograft recipients.

OBJECTIVE: We designed a prospective, randomized, and controlled clinical trial to evaluate the efficacy and safety of achieving a mixed chimerism-associated tolerance protocol for recipients of living related donor (LRD) renal allografts. PATIENTS AND METHODS: Sixty-six consecutive patients were divided into two equal groups of 33 patients with end-stage renal disease. They were enrolled for transplantation after negative lymphocytotoxicity cross-matching (LCM). Both groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory parameters and donor HLA match profiles. The Tn group underwent thymic transplantation of donor renal tissue, two donor-specific transfusions, low-intensity conditioning, and high-dose hematopoietic stem-cell transplantation (HSCT) before renal transplantation. The conditioning regimen included low-dose, target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100 rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d). Unfractionated HSCT procured from the donor marrow was administered into the BM, portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T-cell count less than 10% of normal. This infusion was supplemented with a dose of peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg recipient BW) administered peripherally. Renal transplantation was performed after negative LCM. Donor-specific cytotoxic antibodies were eliminated with intravenous immunoglobulins and plasmapheresis before renal transplantation. Mixed chimerism was evaluated before and after transplantation at monthly intervals in patients with donors of opposite gender by the FISH technique. Both groups received CyA and prednisolone for immunosuppression; Cn subjects also received mycophenolate mofetil/azathioprine. Rejection was treated with standard treatment. Immunosuppression was withdrawn 6 months after renal transplantation for patients with consistently positive chimerism. Clinical tolerance was defined as stable allograft function for more than 100 days without immunosuppression and confirmed by allograft biopsy. RESULTS: Over a mean follow-up of 210 days, all Tn patients showed stable allograft function with mean serum creatinines (SCr) of 1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor-specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn patients are in the process of being weaned off immunosuppression. Mean SCr of controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one (3.03%) graft was lost in controls. No patient was lost in controls. No graft-versus-host disease was observed in Tn patients. CONCLUSION: We have achieved mixed hematopoietic chimerism-associated tolerance with high-dose HSCT, intrathymic donor renal tissue transplantation, and minimal conditioning without any adverse effects.

Central pontine myelinolysis: sequele of hyponatremia during transcervical resection of endometrium.

Transcervical resection of endometrium is an alternative to hysterectomy for women with menorrhagia. The procedure involves the use of cutting loop diathermy to resect the endometrium while the uterine cavity is irrigated with 1.5% glycine which can absorb consequent fluid and electrolyte shifts. Severe hyponatremia leading to central pontine myelinolysis is an extremely rare complication of this procedure. We report a case of a young female undergoing transcervical resection of endometrium for menorrhagia, who developed central pontine myelinolysis but made a complete recovery after three months.

Effect of renal transplantation (surgical stress) on serum levels of oxidants and reducing system.

BACKGROUND: This study attempts to understand the correlation (if any) between surgical stress of renal transplantation and serum levels of pro-oxidant/antioxidants. METHODS: Twenty-four ESRD patients having undergone transplant surgery followed from day-1 to day-10 postsurgery were investigated for serum levels of MDA, SOD, Vit. C and E. The drug regimen received was immunosuppressant, H2 blockers and antihypertensives as per the situation. RESULTS: The typical observations indicated elevated serum levels of MDA from preoperative stage reaching peak value 24 hrs after surgery followed by a steady fall and achieving minima on the 10th day. As regards antioxidants enzyme SOD, Vit. C, Vit. E were low from pretransplant day reaching minima 24 hours postoperatively and returning to normal from 7th day. CONCLUSIONS: The present investigation has amply shown a typical imbalance between pro-oxidant/antioxidants from pretransplant day up to 24 hrs and there after returning to normal level from 7th day suggestive to desired recovery and surgical stress not a limiting factor in way of health progress renal transplant. Dietary intake of Vit. C and E in mega doses can be a good therapeutic measure.

A man with inflamed ears.

A 23-year-old man presented with fever, dyspnea, nonproductive cough, left eye redness, reduced vision, and bilateral ear pain and tenderness. The symptoms had begun two days earlier, eight days after he was discharged from the hospital with a presumptive diagnosis of Still's disease. He was first seen a month before the current admission for complaints of fever (as high as 39.4 degrees C), nonproductive cough, and asymmetric arthritis. The workup at that time included arthrocentesis of the right knee. Analysis of the joint fluid showed 7,500 white blood cells/mm3 and no crystals. A gram stain and culture of the fluid were negative. HIV and hepatitis tests, bone marrow biopsy and culture, transesophageal echocardiography, abdominal computed tomography, radionuclide bone scanning, and rheumatologic tests failed to identify the problem. The development of an evanescent macular pink rash on day 15 suggested the possibility of Still's disease. Treatment with prednisone (40 mg po qd) was initiated, and the patient was discharged on day 19.

Occupational noise exposure and hearing levels.

A study was made at the Bhabha Atomic Research Center to measure the hearing levels of persons working in a noisy environment. Two different workplaces, central air-conditioning plant and glass flowing shops, where a number of persons were exposed to noise levels exceeding 85 dB(A) were chosen. The occupational exposure to noise was determined using a sound level meter, an octave band filter and a personal noise dose meter. The hearing levels of persons exposed to these high levels of noise and a control group not exposed to occupational noise were measured by means of a pure-tone audiometer in a specially-build booth. These persons, aged between 20 to 60 years, were divided into four age groups for the study. The low ambient noise levels in the booth were measured using correlation technique since such low signals cannot be detected by an ordinary sound level meter. The audiometric findings and the results of the noise level survey are discussed in this paper.

Haemorrhagic cholecystitis.

Two cases of haemobilia due to haemorrhagic cholecystitis are presented; only 28 other cases have been described. As there are so many more dramatic causes and treatment for haemobilia it is important for the surgeon to recognize that a common operation will suffice for this rare condition. In both cases bacteria were grown from the bile and it is to be hoped that bile culture will be recorded more commonly in future in cases of this interesting condition.