Impact of Blood Pressure Control on Graft Survival in Kidney Transplant Recipients.

BACKGROUND: Cardiovascular disease is the primary driver of morbidity and mortality in kidney transplant recipients. Hypertension is an important risk factor for development of cardiovascular disease in this population. Despite its important role in post-transplant outcomes, the blood pressure goals for kidney transplant recipients remain elusive. Current guidelines are based on observational data or data extrapolated from the chronic kidney disease population. METHODS: We followed 5-year blood pressure control of 378 kidney-alone transplant recipients at a single center and evaluated patient survival, graft survival, proteinuria, and rate of decline of kidney graft function. RESULTS: We found that a mean systolic blood pressure (BP) of 121 to 130 mm Hg was associated with better graft survival, slower decline of kidney allograft function, and lower degree of proteinuria when compared with a mean systolic BP ≤120 or >130 mm Hg. CONCLUSION: This study provides evidence for strict blood pressure control, systolic BP between 121 and 130 mm Hg, and also cautions against intensive control of systolic BP <120 mm Hg in kidney transplant recipients.

Sexuality, Contraception, and Pregnancy in Kidney Transplantation.

Sexual dysfunction is defined as any abnormality in sexual arousal, libido, intercourse, orgasm, or satisfaction. It is prevalent in patients with chronic and end-stage kidney disease, with 70% to 84% of men and 30% to 60% of women reporting some form of sexual dysfunction. Although kidney transplantation improves the overall quality of life for patients receiving dialysis, it can have unexpected effects on sexual function owing to the use of immunosuppressive medications and comorbid illnesses. It is important to recognize these adverse effects and pre-emptively discuss them with patients to help mitigate consequent psychosocial discontent. Women of reproductive age will often recover fertility after kidney transplantation and therefore need to be empowered to prevent unwanted pregnancies and plan for a safe pregnancy if desired. Complications such as preeclampsia, pregnancy-induced hypertension, gestational diabetes, ectopic pregnancy, still birth, low birth weight, and preterm birth are more common in pregnant women with a kidney transplant. Careful monitoring for infection, rejection, and immunosuppressive dose adjustment along with comanagement by a high-risk obstetrician is of utmost importance. Breast-feeding is safe with most immunosuppressive medications and should be encouraged.

A Systematic Review of Sodium Disorders in HHV-6 Encephalitis.

Human herpesvirus 6 (HHV-6) encephalitis has a high mortality rate. Among those who survive, ~80% develop some type of permanent neurologic disorder. Early diagnosis and treatment may help prevent long-term sequelae. There have been several case reports as well as retrospective and prospective studies associating HHV-6 encephalitis with some form of sodium imbalance, either hyponatremia or hypernatremia; however, the exact frequency post-HCT is unknown, with reports ranging from 30% to 100%. We performed a systematic review of the literature and found 34 cases of HHV-6 encephalitis reported in conjunction with sodium imbalance that documented the timing of that imbalance relative to the onset of encephalitis. Sodium imbalance occurred before or at the onset of HHV-6 encephalitis in all but 2 cases (94%). This finding supports previous suggestions that sodium imbalance can be considered an early indicator of the potential development or presence of HHV-6 encephalitis in at-risk patient populations.

Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes.

The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D) pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs) from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D.

Biomolecular inflammatory response to surgical energy usage in laparoscopic surgery: results of a randomized study.

OBJECTIVE: Use of surgical energy is integral to laparoscopic surgery (LS). Energized dissection (ED) has a potential to impact the biomolecular expression of inflammation due to ED-induced collateral inflammation. We did this triple-blind randomized controlled (RCT) study to assess this biomolecular footprint in an index LS, i.e., laparoscopic cholecystectomy (LC). METHODS AND PROCEDURES: This RCT was conducted in collaboration with tertiary-level institutions, from January 2014 to December 2014 with institutional review board clearance. Consecutive, unselected, consenting candidates for LC were randomized (after anesthesia induction) into group I (ED) and group II (non-ED). They were managed with compliance to universal protocols for ethics, informed consent, anesthesia, drug usage and clinical pathway with blinded observers. Biomolecular inflammatory markers, i.e., interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and highly sensitive CRP (HS-CRP), were measured with blood drawn juxta-preoperatively (H0), at 4 h (H4) and at 24 h (H24). The quantitative changes induced by ED on IL-6, TNF-α and HS-CRP at H0, H4 and H24 with their kinetic behavior were the study endpoint. Prospective data were analyzed statistically with a p value of <0.05 being significant. RESULTS: Two cases from the ED group had biliary injury and hence were withdrawn from analysis. The ED (n = 49) and non-ED (n = 51) groups had similar demographic, clinical and H0 biomolecular variables. There was a significant increase in IL-6, TNF-α and HS-CRP from H0 to H4 in both the groups (p values <0.001). From H4 to H24, all three cytokines showed significant increase in ED group (p < 0.05), whereas in the non-ED group, IL-6 showed significant fall (p = 0.004) and TNF-α showed no significant change (p = 0.063). Both the groups showed H4-H24 elevation of HS-CRP (p = 0.000). CONCLUSION: Energized dissection adds to the cytokine-mediated postoperative inflammation. The additional ED-induced inflammation can be measured objectively by IL-6 and TNF-α levels. CLINICAL TRIALS REGISTRY: Clinical Trials Registry, India (REF/2014/06/007153).

Outcomes of laparoscopic cholecystectomy done with surgical energy versus done without surgical energy: a prospective-randomized control study.

OBJECTIVE: Laparoscopic cholecystectomy (LC), a gold standard procedure can be done without energized dissection (ED). We did a randomized study for the outcomes of LC done with ED or without ED, i.e., with cold dissection (CD). METHODS AND PROCEDURES: At a tertiary level institution, open-ended prospective-randomized control study was conducted between September 2008 and June 2013. Consecutive, unselected, consenting candidates for LC were enrolled following standard ethics, informed consent, anesthesia, and clinical pathway protocol. They were allocated to control group (LC with ED) or study group (LC with CD, as per our published technique with the option for rescue ED). The study points were based upon Clavien-Dindo grading of postoperative complications. They were either, peri-operative events potentially affecting, hospital stay (Grade I) or Grade II-V, e.g., peri-operative hemodynamic instability, needing intervention/blood transfusion, injury to biliary ducts/hollow viscous, postoperative biliary leak, postoperative re-intervention, re-hospitalization, mortality, and any adverse event during a 90-day follow-up period. The data were prospectively collected in an integrated "hospital information system" that could be retrieved only by independent external coordinators. RESULTS: Demographics, co-morbidities, and gallbladder inflammation profile of the control group (n = 361) and study group (n = 384) were comparable. There was no rescue ED usage in the study group. Hospital stay (Grade I adverse outcome dependent) was longer, i.e., 1.6 ± 1.03 in the control versus 1.35 ± 1.2 days in the study group (p < 0.001). Grade II-IV complications were significantly more (p < 0.009) in control group. There was one common bile duct (CBD) injury in each group. The index bilio-enteric anastomosis for CBD injury in control group failed and needed a revision with multiple interventions. There was one grade V adverse outcome, i.e., mortality in the control group. CONCLUSION: Avoiding the use of ED in LC is associated with better outcomes.

Traditional polypropylene and lightweight meshes in totally extraperitoneal inguinal herniorrhaphy.

BACKGROUND: Placement of a prosthetic mesh is integral to successful totally extraperitoneal (TEP) herniorrhaphy. Available meshes have supported the surgical efforts well but search for an ideal mesh continues. Post-herniorrhaphy pain is an index of patient reported outcomes (PRO). The pain is attributable to balloon dissection, cautery, sutures, tackers and prosthesis. Reducing polypropylene content of the mesh is associated with attenuated inflammatory response by the host and improved compliance and comfort. We report the difference in PROs in TEP herniorrhaphy with either heavy polypropylene (PPM) or light weight mesh (LWM) being used for the repair. PATIENTS AND METHODS: From June 2004 to December 2005, consecutive candidates for TEP herniorrhaphy were enrolled for this prospective study with an informed consent and compliance to Ethics guidelines. They were operated under general anesthesia (GA) on a day care basis using either PPM or LWM meshes as per the patient's choice. Operative and postoperative PRO were statistically analyzed by an independent doctor using the Microsoft Office Excel 2003. RESULTS: One hundred fourteen (84 PPMs and 30 LWMs) TEP herniorrhaphies were performed under GA on 57 male patients without any exclusion, on a day care basis. There was no technical difficulty, operative complications, conversion or prolonged hospital stay in either group. Patients of LWM reported better outcome in regards to pain, NSAID usage, seroma and recurrence. All patients of LWM reported an earlier return to activity. CONCLUSION: Light weight meshes result in comparatively better "patient reported outcomes" in TEP inguinal herniorrhaphy as compared to heavy polypropylene meshes.