Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases

Background and aimsPreconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility.Materials and methodsThis was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant.ResultsMedian and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15–42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression.ConclusionSimultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.     

Outcome of low level lasers versus ultrasonic therapy in de Quervain's tenosynovitis

Background:

de Quervain''s tenosynovitis is an inflammation of abductor pollicis longus (APL) and extensor pollicis brevis (EPB) muscle tendon sheaths at the level of radial styloid process. Its conservative management includes nonsteroidal anti-inflammatory drugs, wrist and thumb immobilization, ultrasonic therapy (US Th.) and low level laser therapy (LLLT). Literature is scanty on comparative efficacy of US Th. and LLLT for its management. This prospective study evaluates outcome of US Th. versus LLLT in de Quervain''s disease.

Materials and Methods:

Thirty patients clinically diagnosed de Quervains tenosynovitis were included in the study and randomly assigned to two groups. The average age was 36 years (range: 21-45 years). One group was given LLLT and the other US Th. for a total of 7 exposures on alternate days. The clinical criteria used were Finkelstein''s test, tenderness over radial styloid (Ritchie''s tenderness scale), grip strength, pain (visual analog scale [VAS]) and radiological criteria was ultrasonographic assessment of change in thickness of APL and EPB tendon sheath. They were measured before commencement and at the end of seven sessions of therapy, as per standard procedure.

Results:

Significant improvement was seen within both groups in the following outcome measures assessed: Ritchie''s tenderness scale, grip strength and VAS. Finkelstein''s test was not significantly improved in either groups. Ultrasonographic measurement of tendon sheath diameters, the mediolateral (ML), and anteroposterior (AP) diameters was not found to be significantly different in the US Th. group and the laser therapy group after treatment. On comparing both the groups, no statistically significant difference was found. However, looking at the mean values, the grip strength and VAS showed better improvement in the US Th. group as compared to the laser therapy group.     

Acute appendicitis in the developing world is a morbid disease

IntroductionAcute appendicitis in the developing world has a markedly different disease profile to that in the developed world.MethodsA retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis.ResultsA total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%.Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was £2,060,972.ConclusionsAcute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system.     

A comparison of three dosage regimens of sodium stibogluconate in the treatment of visceral leishmaniasis in Kenya

A prospective randomized trial of three dosage regimens of sodium stibogluconate (Pentostam; Wellcome Foundation, London) to treat visceral leishmaniasis was conducted. Previously untreated patients were randomized to receive 31 doses of sodium stibogluconate (10 mg Sb/kg of body weight per dose) administered once daily for 31 days (group A), every 12 hr for 15 days (group B), or every 8 hr for 10 days (group C). Of the 29 patients who completed treatment, seven of 10 in group B and all of the patients in groups A and C responded to treatment and remained well for one year. One patient in group B failed to respond to treatment, and two others in group B initially responded to treatment but relapsed six weeks after discharge. None of the treatment regimens was toxic. Parasites disappeared from splenic aspirates most quickly and hemoglobin levels rose most rapidly in patients receiving sodium stibogluconate every 8 hr. Treatment of visceral leishmaniasis in Kenya with sodium stibogluconate at a dose of 10 mg Sb/kg every 8 hr for 10 days appears to be a safe alternative to conventional treatment. Its efficacy should be confirmed in a larger number of patients.     

Intestinal permeability to [51Cr]EDTA in infectious diarrhea

Orally administered [⁵¹Cr]EDTA was used to measure intestinal permeability in subjects with infectious diarrhea and in those without gastrointestinal complaints. [⁵¹Cr]EDTA was given to 87 subjects: 63 controls (32 normal controls, and 31 disease controls), and 24 patients with infectious diarrhea. Approximately 100 Ci of [⁵¹Cr]EDTA was given orally after an overnight fast. Urine was collected for the following 24 hr. Intestinal permeability to [⁵¹Cr]EDTA in both normal volunteers and in patients with a variety of diseases not associated with intestinal injury was low and results were in a relatively narrow range. Mean 24-hr urinary excretion of [⁵¹Cr]EDTA, calculated as a percent of the administered dose, in controls was 1.6% (0.2–3.5%). Patients with infectious diarrhea associated with invasive pathogens and/or intestinal inflammation had increased excretion of [⁵¹Cr]EDTA (mean 6.1%,P<0.0001), with elevated excretions in 75%. These results demonstrate that intestinal infections must be considered as possible causes for increased intestinal permeability as assessed by the [⁵¹Cr]EDTA test.     

Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

BackgroundTHEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA_1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.ObjectivesIn these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction–defined major bleeding) and net clinical benefit varied with diabetes-related factors.MethodsOutcomes were analyzed across baseline diabetes duration, HbA_1c, and antihyperglycemic medications.ResultsIn THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA_1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA_1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA_1c, and antihyperglycemic medications.ConclusionTicagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.     

Management of Anticoagulation in Patients with Atrial Fibrillation Undergoing PCI: Double or Triple Therapy?

Purpose of Review

This review aims to discuss the use of antithrombotic therapy in patients with atrial fibrillation who undergo coronary stenting with emphasis on the use of double vs triple therapy.

Recent Findings

When combined with systemic anticoagulation, dual antiplatelet therapy results in an unacceptable increase in bleeding without any improvement in prevention of thrombotic events. Direct oral anticoagulants combined with single antiplatelet therapy have reduced bleeding compared with warfarin plus dual antiplatelet therapy. Triple anticoagulation therapy with warfarin or direct oral anticoagulants leads to an excess of bleeding and is not superior in preventing thrombotic events.

Summary

Recent randomized, controlled trials have shown a significant reduction in major bleeding events in patients treated with dual antithrombotic therapy compared with triple therapy without any difference in efficacy. These findings call into question whether triple therapy should remain a part of standard practice.