A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. METHODS: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. RESULTS: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. CONCLUSIONS: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.

OSTEOPOROTIC FRACTURES DURING BISPHOSPHONATE DRUG HOLIDAY.

OBJECTIVE: Bisphosphonate (BP) drug holidays are recommended to lower the risk of rare adverse events, such as atypical femoral fractures and osteonecrosis of the jaw. However, there are minimal data on the optimal duration of these holidays. Our aim was to determine the clinical and laboratory parameters associated with increased fracture risk in patients on BP drug holiday. METHODS: A retrospective chart review was conducted of 401 patients with osteopenia or osteoporosis who began a BP drug holiday from 2004 to 2013. Collected parameters included demographics, prior therapy, bone mineral density (BMD), bone turnover markers, parathyroid hormone, calcium & vitamin D status, and clinical reports of fractures. RESULTS: Sixty-two (15.4%) patients developed a fracture during follow-up. The yearly incidence of fractures ranged from 3.7 to 9.9%, peaking at 9.9% and 9.8% during years 4 and 5, respectively. The mean age of the fracture group was higher than the nonfracture group, though not significantly different (69.24 ± 12.26 years vs. 66.42 ± 10.18 years; P = .09). Compared to the nonfracture group, the fracture group had lower femoral neck BMD (0.75 ± 0.12 g/cm2 vs. 0.79 ± 0.10 g/cm2; P = .03) and T-scores (-2.13 ± 0.99 vs. -1.78 ± 0.79; P = .01) at baseline. CONCLUSION: Patients who begin BP drug holidays at high risk of fracture based on BMD, age, or other clinical risk factors warrant close follow-up, especially as its duration lengthens. Fracture risk analysis needs to be regularly assessed during the drug holiday and treatment resumed accordingly. ABBREVIATIONS: 25-OHD = 25-hydroxyvitamin D AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology BMD = bone mineral density BP = bisphosphonate BSAP = bone-specific alkaline phosphatase BTM = bone turnover marker FN = femoral neck LS = lumbar spine PTH = parathyroid hormone.

Dedifferentiated chondrosarcoma: A survival analysis of 159 cases from the SEER database (2001-2011).

BACKGROUND AND OBJECTIVES: Dedifferentiated chondrosarcoma is a rare malignancy with reported 5-year overall survival rates ranging from 7% to 24%. The purpose of this investigation is to determine the overall survival of dedifferentiated chondrosarcoma in a modern patient series and how it is impacted by patient demographics, tumor characteristics, and surgical treatment factors. METHODS: This is a retrospective review of the Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2011. Kaplan Meier analyses were used for overall and disease-specific survival. Univariable and multivariable cox regression models were used to identify prognostic factors. RESULTS: Five year overall- and disease-specific survival was 18% (95% CI: 12-26%) and 28% (95% CI: 18-37%), respectively. Individuals with extremity tumors had a worse prognosis than individuals with a primary tumor in the chest wall or axial skeleton (HR 0.20, 95% CI: 0.07-0.56; P = 0.002 and HR 0.60, 95% CI: 0.36-0.99; P = 0.04, respectively). Patients with AJCC stage III or IV disease (HR 2.51, 95% CI: 1.50-4.20; P = 0.001), tumors larger than 8 cm (HR 2.17, 95% CI: 1.11-4.27; P = 0.046), metastatic disease at diagnosis (HR 3.25, 95% CI: 1.98-5.33; P < 0.001), and those treated without surgical resection (amputation: HR 0.43, 95% CI 0.23-0.80; P = 0.01; limb salvage/non-amputation resection: HR 0.41, 95% CI: 0.24-0.69; P = 0.001) had a significant increase in risk of mortality. CONCLUSIONS: The overall prognosis of dedifferentiated chondrosarcoma is poor with a 5-year overall survival of 18%. Patients with a primary tumor located in the chest wall had a better prognosis. Tumors larger than 8 cm, presence of metastases at diagnosis, and treatment without surgical resection were significant predictors of mortality.

Physician Perceptions of Patient Health: A Comparative Analysis between Urologist and Hospitalist Perceptions of Need for Inpatient Hospitalist Comanagement Following Radical Cystectomy.

BACKGROUND/AIMS: The morbidity of radical cystectomy remains high. A multidisciplinary approach utilizing hospitalist comanagement may improve outcomes. It is unclear what factors should be considered to determine which patients might benefit from this approach. We sought to determine if there are differences between the perceived need for co-management between urologists and hospitalists. Preoperative variables were analyzed to determine which factors might be associated with need for comanagement. METHODS: A case-based survey was emailed to urologists and hospitalists at 3 academic institutions to investigate perceptions regarding need for inpatient medical comanagement of fictitious patients following cystectomy. Decisions were rated based on patient comorbidities, age, race, sex, cancer stage, neoadjuvant therapy, alcohol intake, performance status, and English literacy. A Wilcoxon rank sum test assessed each question for differences. A Mantel-Haenszel chi-square test was used to assess whether the proportion of respondents who advocated for comanagement increased as Charlson comorbidity score increased. RESULTS: The most significant determinant of need for postoperative comanagement was patients' comorbidities. Urologists and hospitalists did not differ significantly in beliefs regarding need for comanagement. CONCLUSION: The most important determining factor for comanagement was presence of comorbidities. Further studies are needed to evaluate the impact of this multidisciplinary approach.

Quantitative Analysis of Estimated Burn Size Accuracy for Transfer Patients.

The objective of this study was to quantify differences between estimated TBSA from referring hospitals vs calculated TBSA in the burn unit in regards to several variables. We conducted a retrospective review of 735 burn patients admitted over a 17-month period. Three hundred twenty-six patients fit the criteria of transfers with recorded %TBSA estimations from referring hospitals. Referring %TBSA was compared with actual %TBSA, and the difference was expressed as a percentage of actual %TBSA. This was then used to group referring estimations as underestimated (less than -25%), satisfactory (-25 to 25%), or overestimated (greater than 25%). A paired t-test was used to assess the paired differences for significance. Secondary variables were then assessed between groups. When assessing associations of these clinical measures, a one-way analysis of variance was used for continuous variables and Pearson's χ test or Fisher's exact test was used. Of the 326 patients analyzed, 13 were underestimated, 63 were satisfactory, and 250 were overestimated. The ratio of overestimation to underestimation exceeded 19:1 and the ratio of overestimation to satisfactory estimation was nearly 4:1, with a statistically significant difference in referred %TBSA and actual %TBSA (P < .0001). Within the over and underestimated groups, there were significant differences between referred %TBSA and actual %TBSA (P < .0001). Larger burns were more accurately estimated (P < .0001). There are significant inaccuracies between referring hospital estimated %TBSA and actual %TBSA, which consistently and grossly skew toward overestimation. Inaccuracy in burn size estimation is systemic and can affect patient care and burn unit efficiency.

A Synthesis of Hepatitis C prevalence estimates in Sub-Saharan Africa: 2000-2013.

BACKGROUND: Hepatitis C (HCV) is a deleterious virus that can be cured with new, highly effective anti-viral treatments, yet more than 185 million individuals worldwide remain HCV positive (with the vast majority un-diagnosed or untreated). Of importance, HCV is a leading cause of chronic liver disease and liver cancer, especially in Sub-Saharan Africa (SSA) where the prevalence remains high but uncertain due to little population-based evidence of the epidemic. We aimed to synthesize available data to calculate and highlight the HCV disease burden in SSA. METHODS: Weighted random-effects generalized linear mixed models were used to estimate prevalence by risk cohort, African region (Southern, Eastern, Western, and Central Africa), type of assay used, publication year, and whether the estimate included children. A pooled prevalence estimate was also calculated. Multi-variable analyses were limited to cohort and region specific prevalence estimates in the adult population due to limited studies including children. Prevalence estimates were additionally weighted using the known adult population size within each region. RESULTS: We included more than 10 years of data. Almost half of the studies on HCV prevalence in SSA were from the Western region (49 %), and over half of all studies were from either blood donor (25 %) or general population cohorts (31 %). In uni-variable analyses, prevalence was lowest in Southern Africa (0.72 %), followed by Eastern Africa at 3.00 %, Western Africa at 4.14 %, and Central Africa at 7.82 %. Blood donors consistently had the lowest prevalence (1.78 %), followed by pregnant women (2.51 %), individuals with comorbid HIV (3.57 %), individuals from the general population (5.41 %), those with a chronic illness (7.99 %), and those at high risk for infection (10.18 %). After adjusting for the population size in each region, the overall adult prevalence of HCV in SSA rose from 3.82 to 3.94 %. CONCLUSION: This meta-analysis offers a timely update to the HCV disease burden in SSA and offers additional evidence of the burgeoning epidemic. The study highlights the need to account for type of cohort and region variation when describing the HCV epidemic in SSA, the need for more studies that include children, as well as the need to factor in such variations when planning public health interventions.

Urinary incontinence and diuretic avoidance among adults with chronic kidney disease.

PURPOSE: Diuretics remain an important medication for hypertension management among adults with chronic kidney disease (CKD), but diuretics may also worsen urinary symptoms, especially urinary incontinence (UI). This single-center pilot study examined the prevalence of UI among adults age ≥60 years with CKD using diuretics and assessed diuretic avoidance due to urinary symptoms. METHODS: Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)) and diuretic use were recruited from outpatient nephrology clinics. Urinary symptoms and diuretic avoidance were assessed using standardized questionnaires. RESULTS: The cohort of 44 women and 54 men had a mean age of 71.8 (8.4) years, and urgency-UI, stress-UI and mixed-UI (the presence of both urgency-UI and stress-UI) were reported by 44.9 % (n = 44), 36.7 % (n = 36) and 26.5 % (n = 26), respectively. Nocturia was noted in 68 % (n = 67). Overall, 15.3 % (6 men and 9 women) reported diuretic avoidance. Avoidance of diuretics was 27.3 % (n = 12), 25.5 % (n = 9) and 34.6 % (n = 9) among participants with urgency-UI, stress-UI and mixed-UI, respectively, while only 6.8 % (n = 3) of participants without any UI reported diuretic avoidance. After adjusting for age, sex and diuretic type (loop vs. others), both urgency-UI (odds ratio 5.9 95 % CI 1.5-22.8) and mixed-UI (odds ratio 5.7; 95 % CI 1.6-19.9) were significantly associated with diuretic avoidance compared to participants without urgency-UI, or mixed-UI, respectively. Stress-UI and nocturia were not significantly associated with diuretic avoidance. CONCLUSIONS: UI is common among older adults with CKD receiving diuretics. Patients with urgency-UI are more likely to avoid diuretics.

Sequential opening of IP(3)-sensitive Ca(2+) channels and SOC during alpha-adrenergic activation of rabbit vena cava.

Alpha(1)-aderenoceptor-mediated constriction of rabbit inferior vena cava (IVC) is signaled by asynchronous wavelike Ca(2+) oscillations in the in situ smooth muscle. We have shown previously that a putative nonselective cationic channel (NSCC) is required for these oscillations. In this report, we show that the application of 2-aminoethoxyphenyl borate (2-APB) to antagonize inositol 1,4,5-trisphosphate (InsP(3))-sensitive Ca(2+) release channels (IP(3)R channels) can prevent the initiation and abolish ongoing alpha(1)-aderenoceptor-mediated tonic constriction of the venous smooth muscle by inhibiting the generation of these intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations. The observed effects of 2-APB can only be attributed to its selective inhibition on the IP(3)R channels, not to its slight inhibition of the L-type voltage-gated Ca(2+) channel and the sarco(endo)plasmic reticulum Ca(2+) ATPase. Furthermore, 2-APB had no effect on the ryanodine-sensitive Ca(2+) release channel and the store-operated channel (SOC) in the IVC. These results indicate that the putative NSCC involved in refilling the sarcoplasmic reticulum (SR) and maintaining the tonic contraction is most likely an SOC-type channel because it appears to be activated by IP(3)R-channel-mediated SR Ca(2+) release or store depletion. This is in accordance with its sensitivity to Ni(2+) and La(3+) (SOC blockers). More interestingly, RT-PCR analysis indicates that transient receptor potential (Trp1) mRNA is strongly expressed in the rabbit IVC. The Trp1 gene is known to encode a component of the store-operated NSCC. These new data suggest that the activation of both the IP(3)R channels and the SOC are required for PE-mediated [Ca(2+)](i) oscillations and constriction of the rabbit IVC.