Use of immunoadsorption columns in ABO-incompatible renal transplantation: A prospective study at a tertiary care center in India.

BACKGROUND: We present our experience of ABO-incompatible renal transplant using immunoadsorption (IA) columns. We have compared efficacy of two commercially available columns. METHODS: This single-center prospective study was conducted at Army Hospital Research and Referral, Delhi. All consecutive ABO-incompatible renal transplants from January 2014 to February 2018 were analyzed. Of 30 patients who underwent transplantations, 28 underwent antibody depletion with immunoadsorption columns. Of them, 14 cases were in the "Glycosorb group," while 14 in the "Adsopak group." RESULTS: The donors in the Adsopak group were older than those in the Glycosorb group (p < 0.05). Both groups had spousal donors in majority. The cutoff for the antibody titer was 1:8. The median titer in the Adsopak group was 128 (range, 1:4 to 1:2048), while that in the Glycosorb group was 24 (range, 1:8 to 1:128). All patients in the Glycosorb group had baseline titers ≤1:128, while 13 patients in the Adsopak group had baseline titers ≤1:512. Nil titer was achievable with Glycosorb® (50%,7/14) but not with Adsopak® (P < 0.01). Around 4 sessions were required for the Glycosorb group, while around 8 sessions were required for the Adsopak group before transplantation (p < 0.001). The Glycosorb group was advantageous in terms of graft failure because no rejection was noticed in these patients in their follow-up period. Three patients in the Adsopak group developed rejection (two had mixed rejection, and one had antibody-mediated rejection). Four patients died of sepsis (three in the Glycosorb and one in the Adsopak group). Lower baseline serum creatinine level was achieved in the Glycosorb group. CONCLUSIONS: Results of ABO-incompatible renal transplantation were satisfactory, and the use of immunoadsorption columns could effectively deplete antibody titers. Glycosorb columns were more efficient than Adsopak columns. Graft survival was better with Glycosorb. Posttransplant infections were a major cause of mortality.

Newer Oral Anticoagulant in Chronic Kidney Disease: What we Should Know.

Oral anticoagulants are commonly prescribed in patients with kidney diseases having atrial fibrillation and thromboembolic risk. It is very important to understand their clinical pharmacology and changes that may occur as GFR declines. Risks and benefits of newer oral anticoagulants are different in patients with CKD and patients with ESRD. Patients with GFR < 30 ml/min per 1.73 m2, including those on dialysis, were systematically excluded from landmark trials. All of the NOACs are dependent on renal clearance to some degree and so the risk of NOAC associated bleeding may be expected to be greater in patients with renal failure. Apixaban may be at least as safe as (or possibly safer than) warfarin in individuals with ESRD. Until more data become available, use of dabigatran, rivaroxaban, and edoxaban in patients with CKD stage 5 and ESRD is not indicated. Available strategies for reversing the anticoagulant effect of NOAC are - specific reversal agents available for dabigatran (idarucizumab) and for the oral direct factor Xa inhibitors - andexanet alfa, antifibrinolytic agents, DDAVP and prothrombin complex concentrates (PCCs). In this review clinical and pharmacological aspects of newer oral anticoagulants in the setting of chronic kidney disease will be discussed.

A post-market, prospective, multi-center, single-arm clinical investigation of Phasix™ mesh for VHWG grade 3 midline incisional hernia repair: a research protocol.

BACKGROUND: Incisional heia is a frequent complication of midline laparotomy. The use of mesh in hernia repair has been reported to lead to fewer recurrences compared to primary repair. However, in Ventral Hernia Working Group (VHWG) Grade 3 hernia patients, whose hernia is potentially contaminated, synthetic mesh is prone to infection. There is a strong preference for resorbable biological mesh in contaminated fields, since it is more able to resist infection, and because it is fully resorbed, the chance of a foreign body reaction is reduced. However, when not crosslinked, biological resorbable mesh products tend to degrade too quickly to facilitate native cellular ingrowth. Phasix™ Mesh is a biosynthetic mesh with both the biocompatibility and resorbability of a biological mesh and the mechanical strength of a synthetic mesh. This multi-center single-arm study aims to collect data on safety and performance of Phasix™ Mesh in Grade 3 hernia patients. METHODS: A total of 85 VHWG Grade 3 hernia patients will be treated with Phasix™ Mesh in 15 sites across Europe. The primary outcome is Surgical Site Occurrence (SSO) including hematoma, seroma, infection, dehiscence and fistula formation (requiring intervention) through 3 months. Secondary outcomes include recurrence, infection and quality of life related outcomes after 24 months. Follow-up visits will be at drain removal (if drains were not placed, then on discharge or staple removal instead) and in the 1st, 3rd, 6th, 12th, 18th and 24th month after surgery. CONCLUSION: Based on evidence from this clinical study Depending on the results this clinical study will yield, Phasix™ Mesh may become a preferred treatment option in VHWG Grade 3 patients. TRIAL REGISTRATION: The trial was registered on March 25, 2016 on clinicaltrials.gov: NCT02720042 .

Characteristics of different mesh types for abdominal wall repair in an experimental model of peritonitis.

BACKGROUND: The use of synthetic mesh to repair a potentially contaminated incisional hernia may lead to higher failure rates. A biological mesh might be considered, but little is known about long-term results. Both biological and synthetic meshes were investigated in an experimental model of peritonitis to assess their characteristics in vivo. METHODS: Male Wistar rats were randomized into five groups and peritonitis was induced. A mesh was implanted after 24 h. Five meshes were investigated: Permacol™ (cross-linked collagen), Strattice™ (non-cross-linked collagen), XCM Biologic® (non-cross-linked collagen), Omyra® Mesh (condensed polytetrafluoroethylene) and Parietene™ (polypropylene). The rats were killed after either 30, 90 or 180 days. Incorporation and shrinkage of the mesh, adhesion coverage, strength of adhesions and histology were analysed. RESULTS: Of 135 rats randomized, 18 died from peritonitis. Some 180 days after implantation, both XCM Biologic® and Permacol™ had significantly better incorporation than Strattice™ (P = 0·003 and P = 0·009 respectively). Strattice™ had significantly fewer adhesions than XCM Biologic® (P = 0·001) and Permacol™ (P = 0·020). Thirty days after implantation, Permacol™ had significantly stronger adhesions than Strattice™ (P < 0·001). Shrinkage was most prominent in XCM Biologic® , but no significant difference was found compared with the other meshes. Histological analysis revealed marked differences in foreign body response among all meshes. CONCLUSION: This experimental study suggested that XCM Biologic® was superior in terms of incorporation, macroscopic mesh infection, and histological parameters such as collagen deposition and neovascularization. There must be sufficient overlap of mesh during placement, as XCM Biologic® showed a high rate of shrinkage. Surgical relevance The use of synthetic mesh to repair a potentially contaminated incisional hernia is not supported unequivocally, and may lead to a higher failure rate. A biological mesh might be considered as an alternative. There are few long-term studies, as these meshes are expensive and rarely used. This study evaluated the use of biological mesh in a contaminated environment, and investigated whether there is an ideal mesh. A new non-cross-linked biological mesh (XCM Biologic® ) was evaluated in this experiment. The new non-cross-linked biological mesh XCM Biologic® performed best and may be useful in patients with a potentially contaminated incisional hernia.

Prevention of incisional hernia after midline laparotomy with prophylactic mesh reinforcement: a meta-analysis and trial sequential analysis.

BACKGROUND: Incisional hernia is a frequent complication after abdominal surgery. The aim of this study was to assess the efficacy of prophylactic mesh reinforcement (PMR) after midline laparotomy in reducing the incidence of incisional hernia. METHODS: A meta-analysis was conducted following PRISMA guidelines. The primary outcome was the incidence of incisional hernia after follow-up of at least 12 months. Secondary outcomes were postoperative complications. Only RCTs were included. A random-effects model was used for the meta-analysis, and trial sequential analysis was conducted. RESULTS: Twelve RCTs were included, comprising 1815 patients. The incidence of incisional hernia was significantly lower after PMR compared with sutured closure (risk ratio (RR) 0·35, 95 per cent c.i. 0·21 to 0·57; P < 0·001). Both onlay (RR 0·26, 0·11 to 0·67; P = 0·005) and retromuscular (RR 0·28, 0·10 to 0·82; P = 0·02) PMR led to a significant reduction in the rate of incisional hernia. The occurrence of seroma was higher in patients who had onlay PMR (RR 2·23, 1·10 to 4·52; P = 0·03). PMR did not result in an increased rate of surgical-site infection. CONCLUSION: PMR of a midline laparotomy using an onlay or retromuscular technique leads to a significant reduction in the rate of incisional hernia in high-risk patients. Individual risk factors should be taken into account to select patients who will benefit most. [Correction added on 19 February 2020, after first online publication: J. García Alamino has been amended to J. M. Garcia-Alamino].

ANTECEDENTES: La eventración (hernia incisional) es una complicación frecuente de la cirugía abdominal. El objetivo es evaluar la eficacia de la inserción de una malla profiláctica de refuerzo (prophylactic mesh reinforcement, PMR) después de la laparotomía media para reducir la incidencia de eventración. MÉTODOS: Se realizó un metaanálisis siguiendo las recomendaciones PRISMA. La variable principal fue la incidencia de eventración después de un seguimiento mínimo de 12 meses. Las variables secundarias fueron las complicaciones postoperatorias. Solo se incluyeron ensayos controlados aleatorizados. Se utilizó un modelo de efectos aleatorios para el metaanálisis y se realizó un análisis secuencial de los ensayos. RESULTADOS: Se incluyeron 12 ensayos aleatorizados y controlados con 1.815 pacientes. La incidencia de eventración fue significativamente menor después de la PMR en comparación con el cierre simple (riesgo relativo, RR 0,35; i.c. del 95%: 0,21-0,57, P < 0,0001). Hubo una reducción significativa de la tasa de eventración tanto si la PMR se colocó en posición supra-aponeurótica (RR 0,26; i.c. del 95% 0,11-0,67, P = 0,005) como retromuscular (RR 0,28; i.c. del 95% 0,0-0,82, P = 0,02). La aparición de seromas fue mayor en los pacientes con RPM supra-aponeurótica (RR 2,23; i.c. del 95% 1,10-4,52, P = 0,03). La PMR no conllevó una mayor tasa de infecciones de la herida quirúrgica. CONCLUSIÓN: Una PMR en una laparotomía de la línea media, tanto en posición supra-aponeurótica como retromuscular, reduce de forma significativa el desarrollo de eventraciones en pacientes de alto riesgo. Se deben considerar los factores de riesgo individuales para seleccionar a los pacientes que más puedan beneficiarse.

The feasibility of local anesthesia for the surgical treatment of umbilical hernia: a systematic review of the literature.

BACKGROUND: Yearly approximately 4500 umbilical hernias are repaired in The Netherlands, mostly under general anesthesia. The use of local anesthesia has shown several advantages in groin hernia surgery. Local anesthesia might be useful in the treatment of umbilical hernia as well. However, convincing evidence is lacking. We have conducted a systematic review on safety, feasibility, and advantages of local anesthesia for umbilical hernia repair. METHODS: A systematic review was conducted according to the PRISMA guidelines. Outcome parameters were duration of surgery, surgical site infection, perioperative and postoperative complications, postoperative pain, hernia recurrence, time before discharge, and patient satisfaction. RESULTS: The systematic review resulted in nine included articles. Various anesthetic agents were used, varying from short acting to longer acting agents. There was no consensus regarding the injection technique and no conversions to general anesthesia were described. The most common postoperative complication was surgical site infection, with an overall percentage of 3.4%. There were no postoperative deaths and no allergic reactions described for local anesthesia. The hernia recurrence rate varied from 2 to 7.4%. Almost 90% of umbilical hernia patients treated with local anesthesia were discharged within 24 h, compared with 47% of patients treated with general anesthesia. The overall patient satisfaction rate varied from 89 to 97%. CONCLUSION: Local anesthesia for umbilical hernia seems safe and feasible. However, the advantages of local anesthesia are not sufficiently demonstrated, due to the heterogeneity of included studies. We, therefore, propose a randomized controlled trial comparing general versus local anesthesia for umbilical hernia repair.

Safety of kidney biopsy in elderly: a prospective study.

Kidney biopsy plays an important role in the diagnosis and management of several renal diseases. There is a general reluctance to perform kidney biopsy in elderly due to fear of complications. There is no prospective head to head trial comparing complications of percutaneous kidney biopsy in elderly versus young. This prospective study was undertaken to know the frequency and type of biopsy related complications in elderly. Biopsy was performed using a spring loaded automatic 16 G biopsy gun. Post-biopsy, patients were confined to bed rest for 24 h. A record of intraprocedural problems and post-procedural complications was kept. A total of 210 native kidney biopsies were done of which 26 were performed in elderly patients (61-78 years). Co-morbid conditions were present in 17 patients, some having more than one, hypertension (11), diabetes mellitus (5), chronic obstructive airway disease (6), interstitial lung disease (2) and coronary artery disease (2). Mean serum creatinine was 5.6 mg/dl (range 0.8-14.1 mg/dl). Pre-biopsy dialysis was given to 10 patients. Adequate tissue for histopathological diagnosis was seen in 24 out of 26 biopsies. In two elderly patients biopsy had to be abandoned though indicated due to inability to hold the breath because of underlying lung and cardiac disease. Clinico-pathologic discorrelation was seen in eight patients. Incidence of gross hematuria was more in elderly than in young (4/26 vs. 7/184 P<0.01). Hematuria subsided within 1-2 days in three, one had persistent hematuria for 1 week. Other complications viz. gross hematuria with need of blood transfusions or hemodynamic compromise (0/26 vs. 4/184), perinephric hematoma (0/26 vs. 1/184) and need of intervention (0/26 vs. 1/184) were not higher in the elderly. We conclude that the standard precautions kidney biopsy in elderly is a safe procedure.

Renal infarct following varicella infection.

Renal infarction usually occurs against a background of heart disease or a thromboembolic tendency and rarely is associated with infections. Here we present a case of a young boy who reported with painless gross hematuria following primary Varicella infection and was found to have an isolated renal infarct.

Study of hypothalamic pituitary adrenal axis in patients of membranous nephropathy receiving modified Ponticelli regimen.

Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen) is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA) axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low-dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 µg) was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2%) had low basal cortisol levels, only 3 (23%) had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen.

European Hernia Society guidelines on the closure of abdominal wall incisions.

BACKGROUND: The material and the surgical technique used to close an abdominal wall incision are important determinants of the risk of developing an incisional hernia. Optimising closure of abdominal wall incisions holds a potential to prevent patients suffering from incisional hernias and for important costs savings in health care. METHODS: The European Hernia Society formed a Guidelines Development Group to provide guidelines for all surgical specialists who perform abdominal incisions in adult patients on the materials and methods used to close the abdominal wall. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and methodological guidance was taken from Scottish Intercollegiate Guidelines Network (SIGN). The literature search included publications up to April 2014. The guidelines were written using the AGREE II instrument. An update of these guidelines is planned for 2017. RESULTS: For many of the Key Questions that were studied no high quality data was detected. Therefore, some strong recommendations could be made but, for many Key Questions only weak recommendations or no recommendation could be made due to lack of sufficient evidence. RECOMMENDATIONS: To decrease the incidence of incisional hernias it is strongly recommended to utilise a non-midline approach to a laparotomy whenever possible. For elective midline incisions, it is strongly recommended to perform a continuous suturing technique and to avoid the use of rapidly absorbable sutures. It is suggested using a slowly absorbable monofilament suture in a single layer aponeurotic closure technique without separate closure of the peritoneum. A small bites technique with a suture to wound length (SL/WL) ratio at least 4/1 is the current recommended method of fascial closure. Currently, no recommendations can be given on the optimal technique to close emergency laparotomy incisions. Prophylactic mesh augmentation appears effective and safe and can be suggested in high-risk patients, like aortic aneurysm surgery and obese patients. For laparoscopic surgery, it is suggested using the smallest trocar size adequate for the procedure and closure of the fascial defect if trocars larger or equal to 10 mm are used. For single incision laparoscopic surgery, we suggest meticulous closure of the fascial incision to avoid an increased risk of incisional hernias.

Urinary ascites after an alcohol binge: An uncommon treatable cause of acute kidney injury.

A 38-year-old male presented after a binge of alcohol with acute onset, rapidly progressive distension of abdomen, hematuria, oligoanuria and dialysis dependent renal failure. Evaluation revealed ascitic fluid with high creatinine and computed tomography cystogram showed contrast leak into the peritoneum. Retrograde cystoscopy confirmed rupture of the bladder. He had prompt diuresis after indwelling Foley's catheter was placed. By 2 weeks, he had recovered renal function completely. A high index of suspicion can make an early diagnosis and avoid unnecessary investigations. The mechanism of spontaneous rupture of bladder after an alcohol binge is discussed.

Renal outcome in biopsy proven cases of graft pyelonephritis.

The incidence, risk factors and outcome of graft pyelonephritis are variably described in literature. All patients who had been transplanted at our center between January 2002 and November 2006 and had presented with acute graft dysfunction were subjected to biopsy. Those patients who had neutrophilic casts and interstitial inflammation with predominant neutrophils were included in the study. Out of the 265 patients, 110 were transplanted in the period and underwent biopsy for graft dysfunction. Out of the 110 patients, 26 had biopsy proven acute graft pyelonephritis (AGPN). Nine patients had early AGPN (within 6 months) and the other 17 had late AGPN. Nearly 19% of patients were culture negative and five patients had no clinical features of urinary tract infection; AGPN being a surprise finding on biopsy. Among the risk factors, only hepatitis C virus infection was significantly associated with AGPN. All patients received 4-6 weeks of antibiotics with at least 3 weeks of parenteral antibiotics. Majority (75%) of our patients experienced relapse of AGPN. Graft function was significantly lower 6 months after onset when compared to baseline, portending a poor outcome for these patients. Out of 26, 7 (27%) of our patients had biopsy features of concomitant acute cellular rejection. The treatment of acute rejection, however, did not improve the outcome.

Pneumocystis jiroveci outbreak in a renal transplant center: Lessons learnt.

Pneumocystis jiroveci pneumonia (PJP) is an important opportunistic infection in immunosuppressed hosts. At our center, nine transplant recipients developed PJP over a 4-month period. The median time from transplant was 56 months and none of them was on cotrimoxazole prophylaxis at the time of developing the infection. Over half had been admitted to the renal transplant ward for unrelated indications and contracted the infection in-hospital. Diagnosis was based on microbiological demonstration of P. jiroveci in sputum and/or bronchoalveolar lavage in symptomatic patients. Atypical clinical and radiological signs were common with poor correlation of symptoms to computed tomography findings. Cotrimoxazole therapy was effective; however, patients with pre-existing graft dysfunction developed hyperkalemia commonly (50%). Alternative treatment with clindamycin and primaquine combination was equally effective. Early diagnosis and prompt treatment resulted in low mortality rate (11%). The outbreak was halted after universal use of cotrimoxazole prophylaxis to all patients admitted to the renal transplant ward. We report the first ever outbreak of PJP in Indian renal transplant recipients with possible inter-human transmission of infection in admitted patients.

Iron status, inflammation and hepcidin in ESRD patients: The confounding role of intravenous iron therapy.

Uremia is a state of heightened inflammatory activation. This might have an impact on several parameters including anemia management. Inflammation interferes with iron utilization in chronic kidney disease through hepcidin. We studied the body iron stores, degree of inflammatory activation, and pro-hepcidin levels in newly diagnosed patients with end-stage renal disease (ESRD), and compared them with normal population. In addition to clinical examination and anthropometry, the levels of iron, ferritin, C-reactive protein, tumor necrosis factor alfa, interleukin-6, and prohepcidin were estimated. A total of 74 ESRD patients and 52 healthy controls were studied. The ESRD patients had a significantly lower estimated body fat percentage, muscle mass, and albumin; and higher transferrin saturation (TSAT) and raised serum ferritin. Inflammatory activation was evident in the ESRD group as shown by the significantly higher CRP, IL-6, and TNF-α levels. The pro-hepcidin levels were also increased in this group. Half of the ESRD patients had received parenteral iron before referral. Patients who had received intravenous iron showed higher iron, ferritin, and TSAT levels. These patients also showed more marked inflammatory activation, as shown by the significantly higher CRP, TNF-α, and IL-6 levels. We conclude that our ESRD patients showed marked inflammatory activation, which was more pronounced in patients who had received IV iron. High hepcidin levels could explain the functional iron deficiency. The cause of the relatively greater degree of inflammatory activation as well as the relationship with IV iron administration needs further studies.

Delayed Kounis syndrome and acute renal failure after wasp sting.

A fifty-seven year old gentleman developed hemolysis induced oliguric acute renal failure following multiple wasp stings. Patient was hemodynamically stable on dialytic support. Twelve days later, although the patient was recovering from renal failure, he developed sudden onset of tachyarrythmias and echocardiography demonstrated a Takotsubo type of cardiomyopathy. He was managed with amiodarone and hemodialysis. After two more episodes of deterioration, the patient made full recovery from both the renal and cardiac toxicity. A case of delayed Kounis syndrome associated with Takotsubo cardiomyopathy in the setting of acute renal failure is described. The possible mechanism of such a presentation is discussed.

Posterior reversible encephalopathy syndrome posttransplantation: a case report of possible association with cerebrospinal fluid leak after epidural catheterization.

We have described a case of posterior reversible encephalopathy syndrome (PRES) that developed early in the course of a renal transplant recipient. The patient was on cyclosporine and also had a cerebrospinal fluid (CSF) leak due to migration of an epidural catheter. The possibilities of PRES being associated with administration of cyclosporine and development of a CSF leak are discussed.