Oral bisphosphonate use in the elderly is not associated with acute kidney injury

Intravenous bisphosphonates can cause acute kidney injury; however, this risk was not found with oral bisphosphonates in randomized clinical trials with restrictive eligibility criteria. In order to provide complementary safety data, we studied the risk of acute kidney injury in a population-based cohort of 122,727 patients aged 66 years and older discharged from hospital following a new fragility fracture and no history of bisphosphonate use in the prior year. Bisphosphonate treatment was identified within 120 days after discharge and event rates were measured from 90 days of therapy initiation. The primary outcome was hospitalization with acute kidney injury with secondary outcomes of new nephrology consultation and, in a subset of patients with laboratory values, acute kidney injury was defined as an increase in serum creatinine. We identified 18,286 bisphosphonate users and 104,441 non-users with a mean age of 81 years. Of 5772 patients with laboratory values, 40% had chronic kidney disease (eGFR <60?ml/min per 1.73?m(2)). Overall, there was no statistically significant difference in the risk of acute kidney injury among bisphosphonate users compared to non-users (adjusted odds ratio 1.03), and no significant differences in other outcomes or in subgroups of patients with baseline chronic kidney disease. Thus, in this older population-based cohort, oral bisphosphonate use was not associated with acute kidney injury.     

Point vs. volumetric bladder and rectal doses in combined intracavitary-interstitial high-dose-rate brachytherapy: correlation and comparison with published Vienna applicator data

PurposeWe correlated rectal and bladder point and volumetric dose data in patients treated for advanced cervix cancers with combined intracavitary-interstitial high-dose-rate (HDR) brachytherapy (BT). The results are compared with published Vienna applicator data.Methods and MaterialsWe retrospectively analyzed 30 individual combined intracavitary plus interstitial implants from 10 patients treated with external beam radiation therapy (EBRT) followed by HDR BT for locally advanced cervix carcinoma. EBRT consisted of 45 Gy to the pelvis followed by 9–14.4 Gy boost to involved parametria. BT consisted of a total dose of 21 Gy delivered in 7 Gy fraction. For each implant, CT-image-based simulation and image-guided BT treatment planning was performed. Bladder and rectal doses were evaluated and analyzed using both International commission on Radiation Units and Measurements (ICRU) reference points and dose–volume histograms. The cumulative doses to the rectum and bladder were calculated by combining contributions from external beam therapy and BT. To facilitate comparison with published literature, the total doses were normalized to equivalent dose in 2-Gy fractions (EQD₂) using the equation EQD_2total = EQD_2EBRT + EQD_2BT.ResultsFor the patient population considered, the mean ICRU bladder dose was 75 (±4) Gy₃ compared to bladder D_0.1 cc and D_2 cc doses of 84 (±4) and 78 (±3) Gy₃, respectively. The mean ICRU rectal dose was 73 (±4) Gy₃ compared to rectal D_0.1 cc and D_2 cc doses of 79 (±5) and 74 (±4) Gy₃, respectively. For rectum, the mean dose ratios (D_0.1 cc/D_ICRU) and (D_2 cc/D_ICRU) were 1.08 and 1.01, respectively, compared to Vienna applicator study mean dose ratios of 1.08 and 0.93, respectively. ICRU rectal dose correlated with volumetric rectal doses and best with volumetric D_2 cc dose (r_S = 0.91, p = 0.0003); however, ICRU bladder dose did not correlate with volumetric bladder dose.ConclusionsOur study findings reveal a strong correlation between ICRU rectal reference dose and volumetric rectal D_2 cc dose in combined intracavitary-interstitial HDR brachytherapy. This surrogate rectal–dose relationship is valuable in establishing rectal tolerance dose levels in transitioning from traditional two-dimensional to image-based three-dimensional dose planning.     

Variation in Access to Kidney Transplantation Across Renal Programs in Ontario,Canada

In the United States, kidney transplant rates vary significantly across end‐stage renal disease (ESRD) networks. We conducted a population‐based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1‐, 5‐, and 10‐year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for “healthy” dialysis patients (aged 18–50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow‐up of 11 years). Among 23 022 chronic dialysis patients, the 10‐year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8–10.7%) to 31.4% (95% CI 16.5–47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2–0.5) to 1.5 (95% CI 1.4–1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.     

Use of the Ponseti method for recurrent clubfoot following posteromedial release

Background:

A child with recurrent or incompletely corrected clubfoot after previous extensive soft tissue release is treated frequently with revision surgery. This leads to further scarring, pain and limitations in range of motion. We have utilized the Ponseti method of manipulation and casting and when indicated, tibialis anterior tendon transfer, instead of revision surgery for these cases.

Materials and Methods:

A retrospective review of all children treated since 2002 (n = 11) at our institution for recurrent or incompletely corrected clubfoot after previous extensive soft tissue release was done. Clinical and operative records were reviewed to determine procedure performed. Ponseti manipulation and casting were done until the clubfoot deformity was passively corrected. Based on the residual equinus and dynamic deformity, heel cord lengthening or tenotomy and tibialis anterior transfer were then done. Clinical outcomes regarding pain, function and activity were reviewed.

Results:

Eleven children (17 feet) with ages ranging from 1.1 to 8.4 years were treated with this protocol. All were correctable with the Ponseti method with one to eight casts. Casts were applied until the only deformities remaining were either or both hindfoot equinus and dynamic supination. Nine feet required a heel cord procedure for equinus and 15 required tibialis anterior transfer for dynamic supination. Seven children have follow-up greater than one year (average 27.1 months) and have had excellent results. Two patients had persistent hindfoot valgus which required hemiepiphyseodesis of the distal medial tibia.

Conclusion:

The Ponseti method, followed by tibialis anterior transfer and/or heel cord procedure when indicated, can be successfully used to correct recurrent clubfoot deformity in children treated with previous extensive soft tissue release. Early follow-up has shown correction without revision surgery. This treatment protocol prevents complications of stiffness, pain and difficulty in ambulating associated with multiple soft tissue releases for clubfeet.     

Chronic kidney disease and postoperative mortality: a systematic review and meta-analysis

Whether renal dysfunction is an important factor in postoperative risk assessment has been difficult to prove. In an attempt to provide more compelling evidence, we conducted a systematic review comparing the risk of death and cardiac events in patients with and without chronic kidney disease who underwent elective noncardiac surgery. From electronic databases, web search engines, and bibliographies, 31 cohort studies were selected, evaluating postoperative outcomes in patients with chronic kidney disease. These patients had higher risks of postoperative death and cardiovascular events compared to those with preserved renal function. The pooled incidence of postoperative death was significantly less in those with preserved renal function than in those patients with chronic kidney disease. Meta-regression showed a graded relationship between disease severity and postoperative death. In adjusted analysis, chronic kidney disease had a similar strength of association with postoperative death as diabetes, stroke, and coronary disease. Our review identifies chronic kidney disease as an independent risk factor for postoperative death and cardiovascular events after elective, noncardiac surgery.     

Survival, integration, and axon growth support of glia transplanted into the chronically contused spinal cord

Due to an ever-growing population of individuals with chronic spinal cord injury, there is a need for experimental models to translate efficacious regenerative and reparative acute therapies to chronic injury application. The present study assessed the ability of fluid grafts of either Schwann cells (SCs) or olfactory ensheathing glia (OEG) to facilitate the growth of supraspinal and afferent axons and promote restitution of hind limb function after transplantation into a 2-month-old, moderate, thoracic (T8) contusion in the rat. The use of cultured glial cells, transduced with lentiviral vectors encoding enhanced green fluorescent protein (EGFP), permitted long-term tracking of the cells following spinal cord transplantation to examine their survival, migration, and axonal association. At 3 months following grafting of 2 million SCs or OEG in 6 microl of DMEM/F12 medium into the injury site, stereological quantification of the three-dimensional reconstructed spinal cords revealed that an average of 17.1 +/- 6.8% of the SCs and 2.3 +/- 1.4% of the OEG survived from the number transplanted. In the OEG grafted spinal cord, a limited number of glia were unable to prevent central cavitation and were found in patches around the cavity rim. The transplanted SCs, however, formed a substantive graft within the injury site capable of supporting the ingrowth of numerous, densely packed neurofilament-positive axons. The SC grafts were able to support growth of both ascending calcitonin gene-related peptide (CGRP)-positive and supraspinal serotonergic axons and, although no biotinylated dextran amine (BDA)-traced corticospinal axons were present within the center of the grafts, the SC transplants significantly increased corticospinal axon numbers immediately rostral to the injury-graft site compared with injury-only controls. Moreover, SC grafted animals demonstrated modest, though significant, improvements in open field locomotion and exhibited less foot position errors (base of support and foot rotation). Whereas these results demonstrate that SC grafts survive, support axon growth, and can improve functional outcome after chronic contusive spinal cord injury, further development of OEG grafting procedures in this model and putative combination strategies with SC grafts need to be further explored to produce substantial improvements in axon growth and function.     

Jejunal Gallstone Ileus: An Unusual Site of Gallstone Impaction

Introduction  Gallstone ileus is a life-threatening surgical emergency where characteristic imaging can be diagnostic. Jejunum is the one of the rare sites of gallstone impaction. Materials and Methods  We hereby emphasize the role of multidetector computed tomography (MDCT) by describing a case of jejunal gallstone ileus with cholecystoduodenal fistula in a 59-year-old lady who presented with symptoms and signs of proximal small bowel obstruction. Conclusion  MDCT of the abdomen established the diagnosis, and the patient managed surgically.     

Estimated GFR for Living Kidney Donor Evaluation

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m² based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m², suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web‐based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.     

Perioperative Complications After Living Kidney Donation: A National Study

We integrated the US transplant registry with administrative records from an academic hospital consortium (97 centers, 2008–2012) to identify predonation comorbidity and perioperative complications captured in diagnostic, procedure, and registry sources. Correlates (adjusted odds ratio, aOR) of perioperative complications were examined with multivariate logistic regression. Among 14 964 living kidney donors, 11.6% were African American. Nephrectomies were predominantly laparoscopic (93.8%); 2.4% were robotic and 3.7% were planned open procedures. Overall, 16.8% of donors experienced a perioperative complication, most commonly gastrointestinal (4.4%), bleeding (3.0%), respiratory (2.5%), surgical/anesthesia‐related injuries (2.4%), and “other” complications (6.6%). Major Clavien Classification of Surgical Complications grade IV or higher affected 2.5% of donors. After adjustment for demographic, clinical (including comorbidities), procedure, and center factors, African Americans had increased risk of any complication (aOR 1.26, p = 0.001) and of Clavien grade II or higher (aOR 1.39, p = 0.0002), grade III or higher (aOR 1.56, p < 0.0001), and grade IV or higher (aOR 1.56, p = 0.004) events. Other significant correlates of Clavien grade IV or higher events included obesity (aOR 1.55, p = 0.0005), predonation hematologic (aOR 2.78, p = 0.0002) and psychiatric (aOR 1.45, p = 0.04) conditions, and robotic nephrectomy (aOR 2.07, p = 0.002), while annual center volume >50 (aOR 0.55, p < 0.0001) was associated with lower risk. Complications after live donor nephrectomy vary with baseline demographic, clinical, procedure, and center factors, but the most serious complications are infrequent. Future work should examine underlying mechanisms and approaches to minimizing the risk of perioperative complications in all donors.