Association between post-transplant donor-specific antibodies and recipient outcomes in simultaneous liver–kidney transplant recipients: single-center,cohort study

There is a dearth of published data regarding the presence of post-transplant donor-specific antibodies (DSA), especially C1q-binding DSA (C1q+DSA), and patient and kidney allograft outcomes in simultaneous liver–kidney transplant (SLKT) recipients. We conducted a retrospective cohort study consisted of 85 consecutive SLKT patients between 2009 and 2018 in our center. Associations between presence of post-transplant DSA, including persistent and/or newly developed DSA and C1q+DSA, and all-cause mortality and the composite outcome of mortality, allograft kidney loss, and antibody-mediated rejection were examined using unadjusted and age and sex-adjusted Cox proportional hazards and time-dependent regression models. The mean age at SLKT was 56 years and 60% of the patients were male. Twelve patients (14%) had post-transplant DSA and seven patients (8%) had C1q+DSA. The presence of post-transplant DSA was significantly associated with increased risk of mortality (unadjusted model: Hazard Ratio (HR) = 2.72, 95% confidence interval (CI): 1.06–6.98 and adjusted model: HR = 3.20, 95% CI: 1.11–9.22) and the composite outcome (unadjusted model: HR = 3.18, 95% CI: 1.31–7.68 and adjusted model: HR = 3.93, 95% CI: 1.39–11.10). There was also higher risk for outcomes in recipients with C1q+DSA compared the ones without C1q+DSA. Post-transplant DSA is significantly associated with worse patient and kidney allograft outcomes in SLKT. Further prospective and large cohort studies are warranted to better assess these associations.     

BCG-refractory vs. BCG-relapsing non–muscle-invasive bladder cancer: A prospective cohort outcomes study

PurposePatients with recurrent or persistent high-grade non–muscle-invasive bladder cancer after bacille Calmette-Guérin (BCG) therapy are termed “BCG failures.” We hypothesize that BCG-refractory patients who fail to respond to BCG have worse outcomes after bladder-sparing treatments compared with BCG-relapsing patients whose tumors recur after at least a 6-month disease-free interval.Materials and methodsWe screened 32 patients who had failed BCG therapy for eligibility in a multicenter investigational trial. BCG-refractory patients received instillations of a mycobacterial cell wall–DNA complex extract. BCG-relapsing patients were treated with additional BCG or other intravesical agents. Both groups of patients were followed prospectively with transurethral biopsy after 6 months, and cystoscopy every 3 to 6 months for more than 2 years. Median follow-up time for all patients was 53 months (range: 24–72 mo).ResultsSeventeen patients were classified as BCG refractory and 15 patients defined BCG relapsing. Recurrence-free median survival time was 10 months for BCG-refractory patients receiving mycobacterial cell wall–DNA complex vs. 23 months for BCG-relapsing patients who received another induction course of BCG therapy (P = 0.002). Progression-free survival time was 18 months for BCG-refractory vs. 52 months for BCG-relapsing patients (P = 0.001). Of the 17 BCG-refractory patients, 8 (47%) have died vs. 3 (20%) of the 15 BCG-relapsing patients.ConclusionsBCG-refractory and BCG-relapsing categories differentiate BCG-failed patients into high-and lower-risk prognostic groups that may be useful in guiding treatment strategies.     

Association between folic acid,homocysteine, vitamin B12 and erectile dysfunction—A cross-sectional study

To evaluate the relationship between serum levels of folic acid (FA), homocysteine (HCY), vitamin B12 (B12) and erectile dysfunction (ED) and to explore their internal relationships. The study included 134 ED patients and 50 healthy controls. ED was assessed using IIEF-5 scores. ED group had lower median FA (6.08 versus 10.21; p < .001) and B12 (256.0 versus 337.5; p < .001) levels, and higher median HCY (11.4 versus 7.95; p < .001) levels, and these differences seemed to be more pronounced in the younger participants (age < 35 yr). FA decreased with the severity of ED (7.52 versus 6.15 versus 5.49 versus 3.97; p < .001), while HCY increased (10.35 versus 11.8 versus 12.9 versus 15; p < .001). Smoking and shift work were associated with lower FA levels. Multivariate analysis showed that serum FA and HCY revealed significant relation with ED. ROC analysis showed that FA ≤ 8.84 and HCY ≥ 10.35 were the best cut-off values for ED diagnosis. Both FA (r = −0.703, p < .001) and B12 (r = −0.576, p < .001) were negatively correlated with HCY. In conclusion, low FA levels and high HCY levels might be independent risk factors for ED. Low serum FA and B12 levels might co-cause high HCY levels and lead to ED.     

Is there relationship between serum uric acid levels and lower urinary tract symptoms,prostate volume,and PSA in men without cancer? A prospective population-based study

There are conflicting results about uric acid (UA) effect on the prostate. We investigated the relationship between UA and PSA, free PSA, prostate volume and international prostate symptoms score (IPSS) in benign prostate hyperplasia (BPH). This study was conducted in BPH men without cancer who were referred for annual health workup (N = 910) from 2017 to 2020. The mean ages were 67.28 ± 9.2 years. UA was positively related to IPSS and PSA (r = 0.210, p = .023 and r = 0.156, p = .041 respectively) and also negatively related to free/total PSA ratio (r = −0.332, p = .01) but not related to prostate volume (r = 0.036, p = .696). After adjustment for age, BMI and prostate volume, there were significant relationships between hyperuricaemia and PSA, free/total PSA ratio, and IPSS (95% CI: 0.254–1.645, OR = 0.647, p = .039; 95% CI: 0.076–0.899, OR = 0.270, p = .033 and 95% CI: 1.011–3.386, OR = 1.851, p = .038 respectively). These results should be considered during the general assessment of the patients with BPH. The findings raise the possible hypothesis of relationship between serum UA with IPSS and PSA which should be investigated by future studies.     

Impact of bariatric surgery on surveillance and treatment outcomes of Barrett’s esophagus: A stage-matched cohort study

BackgroundObesity could increase the risk of Barrett’s esophagus (BE). Roux-en-Y gastric bypass (RYGB) could alter the natural course of BE. Data on BE progression after RYGB are scarce.ObjectivesTo study endoscopic surveillance and endoscopic eradication therapy (EET) outcomes of BE in post-RYGB patients versus controls with obesity.SettingAcademic referral centers, a retrospective cohort study.MethodsPatients who underwent RYGB with biopsy-proven BE or intramucosal esophageal adenocarcinoma (IM-EAC) with an endoscopic follow-up of at least 12 months were identified from a prospectively maintained database between January 1992 and February 2019 at 3 tertiary care centers. RYGB patients were matched 1-to-2 to patients with obesity (body mass index > 30 kg/m²) by the initial BE stage at diagnosis. Surveillance and EET outcomes were compared.ResultsA total of 147 patients were included (49 RYGB and 98 BE stage-matched controls with obesity). For endoscopic surveillance, the rate of disease progression to high-grade dysplasia /IM-EAC was significantly lower in the RYGB patients than controls (2.6% versus 40.2%, respectively; P < .0001), with a comparable median follow-up time (85 months versus 80 months, respectively). This effect persisted in a multivariate analysis, with a hazard ratio of .09 (95% confidence interval, .01–.69). For EET, no difference in the rate of achieving complete remission of intestinal metaplasia was observed between the RYGB and control groups (71.2% versus 81.3%, respectively; P = .44).ConclusionRYGB appears to be a protective factor for disease progression to neoplastic BE during endoscopic surveillance. However, disease progression was still observed after RYGB, warranting continuing endoscopic surveillance. EET appeared to be equally effective between RYGB patients and controls with obesity.     

Vitamin D levels in Irish children with fractures: A prospective case–control study with 5 year follow-up

IntroductionTwenty-five-hydroxy-vitamin D3 (25-OH-vit D) is a prohormone that is essential for normal calcium homeostasis and bone metabolism. Understanding its role is an important component of the proper care of the pediatric orthopaedic patient. The aim of this study was to determine whether children in Ireland with fractures have increased prevalence of 25-OH-Vit D deficiency compared with age matched controls and to ascertain the relationship between a low 25-OH-vit D level and the incidence of fractures in Irish children. We hypothesised that children presenting to our centre following a fracture would have significantly lower 25-OH-vit D.MethodsA prospective case–control study at a large urban tertiary referral academic hospital located in Dublin, Ireland was completed over a 14 month period from June 2014 to August 2015. A total of 116 subjects, distributed as cases (n = 58) and controls (n = 58) were included in this study. Whole blood (10 ml) was taken in two serum bottles from each patient. Serum 25-hydroxy-vitamin D3 levels were measured. An age matched control group was generated from other children attending the hospital, who also had vitamin D levels measured for different clinical reasons. We followed up both the fracture and control group for the next 5 years to assess the repeat fracture rate.ResultsFifty-eight patients with a fracture requiring operative intervention, were included in the study. Statistical analysis was performed comparing to 58 age and sex-matched controls. The mean vitamin D level for the fracture group was 63.2 nmol/L (SD = 27.3), which was higher than the mean of the controls (62.5 nmol/L) (SD = 21.3) (p = 0.86), but this difference was found not to be statistically significant in unadjusted analysis. There was no statistically significant difference in the number of patients classified with low serum Vitamin D levels (<50 nmolL), with the fracture group consisting of 22 (37.9%) patients, and the control group of 17 patients (29.3%) (p = 0.33) with a level below 50 nmol/L. At five-year follow-up, 11 of the 58 patients (18.9%) in the fracture group went on to have a further fracture compared with eight patients (13.7%) from the control group. Out of these 11 from the fracture group five (45.45%) had been found to have a low serum 25-OH-Vit D level five years previously. Out of the eight controls that presented with a fracture within the five-year period, 3 (37.5%) had had a low vitamin D level at the origin of this study.ConclusionThe results of this study show that children presenting to our institution with low energy fractures have a prevalence of 38% 25-hydroxy-vitamin D deficiency. This study included children from age 1 to 16 primarily Caucasian encompassing all fracture types resulting from accidental trauma. Our findings suggest that in an Irish pediatric population vitamin D status may impact fracture risk with more than one-third being deficient in this review.     

Donor cardiac arrest and cardiopulmonary resuscitation: impact on outcomes after simultaneous pancreas–kidney transplantation – a retrospective study

Donor cardiac arrest and cardiopulmonary resuscitation (CACPR) has been considered critically because of concerns over hypoperfusion and mechanical trauma to the donor organs. We retrospectively analyzed 371 first simultaneous pancreas–kidney transplants performed at the Medical University of Innsbruck between 1997 and 2017. We evaluated short- and long-term outcomes from recipients of organs from donors with and without a history of CACPR. A total of 63 recipients received a pancreas and kidney graft from a CACPR donor. At 1, and 5-years, patient survival was similar with 98.3%, and 96.5% in the CACPR and 97.0%, and 90.2% in the non-CACPR group (log rank P = 0.652). Death-censored pancreas graft survival was superior in the CACPR group with 98.3%, and 91.4% compared to 86.3%, and 77.4% (log rank P = 0.028) in the non-CACPR group, which remained statistically significant even after adjustment [aHR 0.49 (95% CI 0.24–0.98), P = 0.044]. Similar relative risks for postoperative complications Clavien Dindo > 3a, pancreatitis, abscess, immunologic complications, delayed pancreas graft function, and relative length of stay were observed for both groups. Donors with a history of CACPR are, in the current practice, safe for transplantation. Stringent donor selection and short CPR durations may allow for outcomes surpassing those of donors without CACPR.     

Association between bone stiffness and nutritional biomarkers combined with weight-bearing exercise,physical activity,and sedentary time in preadolescent children. A case–control study

Physical activity (PA) and micronutrients such as calcium (Ca), vitamin D (25OHD), and phosphate (PO) are important determinants of skeletal development. This case–control study examined the association of these nutritional biomarkers and different PA behaviours, such as habitual PA, weight-bearing exercise (WBE) and sedentary time (SED) with bone stiffness (SI) in 1819 2–9-year-old children from the IDEFICS study (2007–2008). SI was measured on the calcaneus using quantitative ultrasound. Serum and urine Ca and PO and serum 25OHD were determined. Children's sports activities were reported by parents using a standardised questionnaire. A subsample of 1089 children had accelerometer-based PA data (counts per minute, cpm). Moderate-to-vigorous PA (MVPA) and SED were estimated. Children with poor SI (below the 15th age-/sex-/height-specific percentile) were defined as cases (N = 603). Randomly selected controls (N = 1216) were matched by age, sex, and country. Odds ratios (OR) for poor SI were calculated by conditional logistic regression for all biomarkers and PA behaviour variables separately and combined (expressed as tertiles and dichotomised variables, respectively). ORs were adjusted for fat-free mass, dairy product consumption, and daylight duration. We observed increased ORs for no sports (OR = 1.39, p < 0.05), PA levels below 524 cpm (OR = 1.85, p < 0.05) and MVPA below 4.2% a day (OR = 1.69, p < 0.05) compared to WBE, high PA levels (< 688 cpm) and high MVPA (6.7%), respectively. SED was not associated with SI. ORs were moderately elevated for low serum Ca and 25OHD. However, biomarkers were not statistically significantly associated with SI and did not modify the association between PA behaviours and SI. Although nutritional biomarkers appear to play a minor role compared to the osteogenic effect of PA and WBE, it is noteworthy that the highest risk for poor SI was observed for no sports or low MVPA combined with lower serum Ca (< 2.5 mmol/l) or lower 25OHD (< 43.0 nmol/l).     

Do laryngeal mask airway devices attenuate liquid flow between the esophagus and pharynx? A randomized, controlled cadaver study

In this randomized, controlled cadaver study, we tested the hypothesis that the standard laryngeal mask airway (LMA) and flexible laryngeal mask airway (FLMA) attenuate liquid flow between the esophagus and pharynx. Fifty fresh cadavers were studied in four LMA groups. Ten female cadavers had a size 4 LMA and 10 had a size 4 FLMA; 10 male cadavers had a size 5 LMA and 10 had a size 5 FLMA; 5 male and 5 female cadavers functioned as controls. The chest was opened, and the infusion set of a pressure-controlled, continuous flow pump was inserted into the esophagus and ligated into place. Esophageal pressure was increased in 2-cm H2O increments. Regurgitation pressure was the esophageal pressure at which fluid was first seen with a fiberoptic scope in the hypopharynx (control group) and above the cuff or within the bowl (LMA groups). This was performed in the LMA groups at 0-40 mL cuff volume in 10-mL increments. Mean (95% confidence interval) regurgitation pressure for the control group was 7 (6-8) cm H2O and for the LMA groups combined was 19 (17-20) cm H2O at 0 mL cuff volume, 47 (41-52) cm H2O at 10 mL, 51 (44-55) cm H2O at 20 mL, 52 (45-56) cm H2O at 30 mL, and 52 (45-55) cm H2O at 40 mL. The increase in regurgitation pressure with increasing cuff volume from 0 to 10 mL was statistically significant (P < 0.0001). Regurgitation pressure was higher for the LMA groups at all cuff volumes compared with the control group (P < 0.0001). There were no differences in regurgitation pressure among the LMA groups. We conclude that the correctly placed LMA and FLMA attenuate liquid flow between the esophagus and pharynx. Implications: We have shown, in cadavers, that the correctly placed standard and flexible laryngeal mask airways attenuate liquid flow between the pharynx and esophagus.     

Abnormal serum levels of magnesium,phosphate, and zinc in ICU patients—Characteristics,management, and outcomes: The WhyTrace cohort study

Background

Abnormal serum levels of magnesium, phosphate, and zinc appear common in intensive care unit (ICU) patients, but the epidemiology, management, and associations with outcomes are less well described. We described these factors and estimated associations with outcomes in a large dataset of Danish ICU patients.

Methods

We included adults who were acutely admitted to 10 general ICUs in Denmark between October 2011 and January 2018. From the dataset, we obtained characteristics of patients who had serum levels measured of magnesium, phosphate, or zinc, including data on supplementation. We used joint models with death as a competing outcome to estimate the associations between abnormal serum levels and time to successful extubation and, for magnesium, also incident tachyarrhythmia.

Results

We included 16,517 of 36,514 patients in the dataset. The cumulative probability of hypomagnesemia within 28 days was 64% (95% confidence interval [CI] 62–66); of hypophosphatemia 74% (95% CI 72–75); and of hypozincemia 98% (95% CI 98–98). Supplementation of magnesium was used in 3554 out of 13,506 (26%) patients, phosphate in 2115 out of 14,148 (15%) patients, and zinc in 4465 out of 9869 (45%) patients. During ICU stay, 38% experienced hypermagnesemia, 58% hyperphosphatemia, and 1% hyperzincemia. Low serum levels of magnesium, phosphate, and zinc were associated with shorter time to successful extubation, and high serum magnesium and phosphate and low serum zinc with the competing risk of increased mortality, but too few serum measurements made the results inconclusive.

Conclusion

In this multicenter cohort study of acutely admitted ICU patients, most experienced low serum levels of magnesium, phosphate, or zinc during ICU stay, many received supplementation, and experiencing both low and high serum levels during ICU stay was not uncommon. Associations between serum levels and clinical outcomes appeared inconclusive because the data proved unfit for these analyses.     

Palmar wrist ganglion: does intervention improve outcome? A prospective study of the natural history and patient-reported treatment outcomes

A prospective cohort study was undertaken to observe the long-term outcome of different treatments for palmar wrist ganglia. One hundred and eighty-two patients agreed to participate in the study. One hundred and fifty-five patients (88%) responded at 2 or 5 years. Seventy-nine had been treated by surgical excision, 39 by aspiration and 38 by reassurance alone. At 5 years no significant differences were observed in the recurrence rates which were 42% after excision of a palmar wrist ganglion and 47% (19 of 39) after aspiration. Twenty of the 39 untreated ganglia had disappeared spontaneously. Eighty-five per cent of the patients were satisfied irrespective of treatment. Patients having surgery had a complication rate of 20% and took more time off work (14 days). Significantly more patients in the untreated group felt the persistent ganglion was unsightly. The patient evaluation measure scores were similar. At 2 and 5 year follow-up, regardless of treatment, no difference in symptoms was found, regardless of whether the palmar wrist ganglion was excised, aspirated or left alone. One in four wrists remained weak regardless of treatment or disappearance of the ganglion.     

Racial/ethnic disparities in penile squamous cell carcinoma incidences,clinical characteristics,and outcomes: A population-based study, 2004–2016

PurposeThis study assessed the impact of race/ethnicity on penile squamous cell carcinoma (PSCC) incidence rates, clinical characteristics, and outcomes.Materials and methodsSurveillance, Epidemiology and End Results data from 2004 to 2016 was used for this study. We evaluated racial/ethnic differences in clinical characteristics using χ² tests. Overall survival (OS) and PSCC-specific survival (PSCC-SS) were estimated using the Kaplan-Meier method, and differences were determined using the log-rank test. Cox regression models were performed to assess independent predictors for PSCC patient survival.ResultsA total of 2,720 PSCC patients were included for incidence analysis, and 2,438 patients were identified for the χ² testing and survival analyses.The overall incidence of PSCC during 2004 to 2016 was 0.30 per 100,000. Only non-Hispanic white (NHW) patients had a statistically significant increase in age-adjusted incidence rates (annual percent change = 2.26, 95% confidence interval [CI]: 0.78–3.76; P = 0.01). In univariate analysis, race/ethnicity was an independent prognostic factor for OS and PSCC-SS. After adjusting for age, marital status, income, grade, TNM (tumor, node, metastasis) stage, and treatment strategies, non-Hispanic black patients still had a statistically significant hazard ratio of 1.35 (95% CI: 1.08–1.68; P = 0.007) for OS, and a hazard ratio of 1.36 (95% CI: 1.01–1.82; P = 0.045) for PSCC-SS compared to NHW.ConclusionNHW patients had a statistically significant increase in age-adjusted incidence rate during the period 2004 to 2016. Race/ethnicity is an independent prognostic factor for OS and PSCC-SS, and non-Hispanic black were proven to have unfavorable OS and PSCC-SS compared with NHW.     

Registry of the Japanese Society of Lung and Heart–Lung Transplantation: official Japanese lung transplantation report, 2014

The number of organ donations after brain death has significantly increased since the revised Japanese Organ Transplant Law took effect in July 2010. Sixty-one lung transplantations were conducted throughout Japan in 2013, including 20 living-donor lung transplantations and 41 brain-dead-donor lung transplantations (23 bilateral lungs, 17 single lungs, and 1 heart–lung transplantation). The number of lung transplant candidates newly registered at the Japan Organ Transplantation Network also increased to 126 in 2013, suggesting a severe donor shortage in Japan. More than 60 % of offered brain-dead-donor, lungs were used for transplantation, indicating the effort of Japanese lung transplant centers to overcome the challenge of donor shortage. After lung transplantation, patients generally enjoyed a good quality of life with excellent survival of 86.2 % at 1 year, 79.6 % at 3 years, and 73.7 % at 5 years post-transplantation. There was no significant difference in patient survival between living-donor and brain-dead-donor lung transplantation. Early mortality of lung transplant recipients within 90 days was attributable to graft failure followed by infection, while long-term mortality was mostly explained by chronic lung allograft dysfunction (chronic rejection), infection, and malignancy. Eight lung transplant centers are currently approved to conduct lung transplantation in Japan (Tohoku, Dokkyo, Chiba, Kyoto, Osaka, Okayama, Fukuoka, and Nagasaki Universities). These centers are expected to continue to make a special effort to save critically ill patients waiting for lung transplantation.