Diagnostics of DNA fragmentation in human spermatozoa: Are sperm chromatin structure analysis and sperm chromatin dispersion tests (SCD‐HaloSpermG2®) comparable?

Men affected with idiopathic infertility often display basic spermiogramme values similar to fertile individuals, questioning the diagnostic impact of the World Health Organization (WHO) thresholds used. This study explored sperm DNA fragmentation in single ejaculates from 14 fertile donors and 42 patients with idiopathic infertility providing semen for assisted reproductive techniques in a university fertility clinic. Each ejaculate was simultaneously studied for sperm DNA fragmentation by the flow cytometer‐based sperm chromatin structure analysis (SCSA) and the new light‐microscopy‐based sperm chromatin dispersion assay (SCD‐HaloSpermG2^®), before and after sperm selection for in vitro fertilisation with a colloid discontinuous gradient. The WHO semen variables did not differ between groups, but DNA fragmentation after SCSA (DFI) or SCD (SDF) was significantly (p < 0.05) higher in patients (DFI: 40.2% ± 3.0 vs. SDF: 40.3% ± 1.4) than in fertile donors (DFI: 17.1% ± 2.1 vs. SDF: 20.9% ± 2.5). Sperm selection led to lower proportions of DNA‐fragmented spermatozoa (DFI: 11.9 ± 1.7 vs. SCD: 10.0 ± 0.9, p < 0.05). The techniques output correlated highly and significantly (r² = 0.82). DNA fragmentation is confirmed as a relevant variable for scrutinising patients with idiopathic infertility, beyond the evidently insufficient WHO semen analyses. Since both techniques yielded similar results, the reduced necessity of complex equipment when running SCD ought to be considered for a clinical setting.     

Effect of everolimus vs calcineurin inhibitors on quality of life in heart transplant recipients during a 3‐year follow‐up: Results of a randomized controlled trial (SCHEDULE)

The Sc andinavian he art transplant everolimus d e novo st u dy with ear l y calcineurin inhibitors avoidanc e (SCHEDULE) trial was a 12 month, randomized, open‐label, parallel‐group trial that compared everolimus (EVR; n=56) to conventional CsA (n=59) immunosuppression. Previously, we reported that EVR outperformed CsA in improving renal function and coronary artery vasculopathy, despite a higher rejection rate with EVR. This study aimed to compare the effects of these treatments on quality of life (QoL). Within five post‐operative days, patients (mean age 50±13 years, 27% women) were randomized to EVR or a standard CsA dosage (CsA group). This study assessed quality of life (QoL), based on the Short Form‐36, EuroQol‐5D, and Beck Depression Inventory (BDI). Assessments were performed pre‐HTx and 12 and 36 months post‐HTx. At 12 and 36 months, the groups showed similar improvements in Short Form‐36 measures (at pre‐HTx, 12 and 36 months the values were as follows: Physical component summary: EVR: 31.5±110.9, 49.1±9.7, and 47.9±10.6; P<.01; CsA: 32.5±8.2, 48.4±8.5, and 46.5±11.5; P<.01; mental component summary: EVR: 46.0±12.0, 51.7±11.9, and 52.1±13.0; P<.01; CsA: 38.2±12.5, 53.4±7.1, and 54.3±13.0; P<.01); similar decrease in mean BDI (EVR: 10.9±10.2, 5.4±4.7, and 8.1±9.0; P<.01; CsA: 11.8±7.1, 6.3±5.4, and 6.2±6.5; P<.01); and similar Euro Qol‐improvements. Thus, in this small‐sized study, EVR‐based and conventional CsA immunosuppressive strategies produced similar QoL improvements.     

An additional marker for sperm DNA quality evaluation in spermatozoa of male partners of couples undergoing assisted reproduction technique (IVF/ICSI): Protamine ratio

The aim of this study was to evaluate the relationship between the protamine ratio (P1/P2), DNA fragmentation of spermatozoa and protamine deficiency. Patients were grouped into fertile (G1; n = 151) and sub‐fertile (G2; n = 121). DNA fragmentation in spermatozoa was analysed by a TUNEL assay (terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling), and the protamination was determined by CMA3 staining, while Western blot was used to measure protamine P1 and P2. While sperm DNA fragmentation (SDF) and protamine ratio were significantly elevated in G2 compared with G1 (12.31 ± 7.01% vs. 17.5 ± 9.5%; p = .001) and (0.91 ± 0.43 vs. 0.75 ± 0.42; p = .003); respectively, the CMA3 positive showed no difference at all between G1 and G2. In G1, the CMA3 positive correlated negatively with the P1/P2 ratio and SDF (r = ?.586, r = ?.297; p = .001 respectively). In contrast, the protamine ratio correlated positively with SDF (r = .356; p = .001). In G2, no correlation was observed between CMA3 positive, SDF and the P1/P2 ratio but the P1/P2 ratio showed a positive correlation with SDF (r = .479; p = .001). In conclusion, the spermatozoa DNA deterioration was closely associated with abnormal protamination but showed an association with the protamine ratio, more than with CMA3 positive. Therefore, for the evaluation of DNA damage in spermatozoa, the P1/P2 ratio might act as an additional biomarker.     

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD‐6 estimated glomerular filtration rate (e‐GFR) <40 mL/min/1.73 m² for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver‐kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD‐6 e‐GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m², P=.002), higher 24‐hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post‐LTA, the e‐GFR (mL/min/1.73 m²) increased in all nine patients, with mean e‐GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre‐LTA e‐GFR (P≤.005 at all time points). One patient developed end‐stage renal disease 9 years post‐LTA and another patient expired 7 years post‐LTA. The low e‐GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.     

Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO₂/FiO₂ was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low‐flow, open atrium and low hematocrit technique. Thirty‐five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO₂/FiO₂ (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X‐ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD₇₂ grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).     

Lidocaine vs. magnesium: effect on analgesia after a laparoscopic cholecystectomy

Background: This double‐blinded study aimed at evaluating and comparing the effects of magnesium and lidocaine on pain, analgesic requirements, bowel function, and quality of sleep in patients undergoing a laparoscopic cholecystectomy (LC). Methods: Patients were randomized into three groups (n=40 each). Group M received magnesium sulfate 50 mg/kg intravenously (i.v.), followed by 25 mg/kg/h i.v., group L received lidocaine 2 mg/kg i.v., followed by 2 mg/kg/h i.v., and group P received saline i.v. Bolus doses were given over 15 min before induction of anesthesia, followed by an i.v. infusion through the end of surgery. Intraoperative fentanyl consumption and averaged end‐tidal sevoflurane concentration were recorded. Abdominal and shoulder pain were evaluated up to 24 h using a visual analog scale (VAS). Morphine consumption was recorded at 2 and 24 h, together with quality of sleep and time of first flatus. Results: Lidocaine or magnesium reduced anesthetic requirements (P<0.01), pain scores (P<0.05), and morphine consumption (P<0.001) relative to the control group. Lidocaine resulted in lower morphine consumption at 2 h [4.9 ± 2.3 vs. 6.8 ± 2.8 (P<0.05)] and lower abdominal VAS scores compared with magnesium (1.8 ± 0.8 vs. 3.2 ± 0.9, 2.2 ± 1 vs. 3.6 ± 1.6, and 2.1 ± 1.4 vs. 3.3 ± 1.9) at 2, 6, and 12 h, respectively (P<0.05). Lidocaine was associated with earlier return of bowel function and magnesium was associated with better sleep quality (P<0.05). Conclusion: I.v. lidocaine and magnesium improved post‐operative analgesia and reduced intraoperative and post‐operative opioid requirements in patients undergoing LC. The improvement of quality of recovery might facilitate rapid hospital discharge.     

Evaluation of lithogenic elements in urine of healthy newborns

The determination of urinary excretion of lithogenic elements in healthy newborns involves factors ranging from urine collection and data handling to maternal influences, which can cause difficulties in analyzing the results. The objective of this study was to determine normal values of parameters related to lithogenesis, such as calcium, uric acid, citrate, and oxalate, in urine of healthy newborns using isolated samples, focusing on variations according to gender, weight, milk ingestion, and family history of lithiasis. Parameters measured in isolated urine samples from 104 healthy newborns (77 males and 27 females) were corrected by creatinine. The ratios were expressed as milligram/milligram of creatinine: calcium/creatinine of 0.10±0.01 (X±SE), uric acid/ creatinine of 1.10±0.10, citrate/creatinine of 0.56±0.04, and oxalate/creatinine of 0.07±0.01. Differences were observed between males and females, in terms of uric acid (0.80±0.07 vs. 1.10±0.10 mg/mg, P<0.05), citrate (0.05±0.06 vs. 0.17±0.05, P<0.05), sodium (0.17± 0.01 vs. 0.05±0.01, P<0.001), and potassium (0.05± 0.01 vs. 0.20±0.02, P<0.001). Interestingly, the urinary concentration of protector factors such citrate and potassium was higher in females than in males with low sodium excretion. Artificial milk feeding leads to higher calcium (0.10±0.06 vs. 0.06±0.01), uric acid (1.40±0.20 vs. 0.90±0.09, P<0.05), citrate (0.90±0.09 vs. 0.50±0.04, P<0.001), and oxalate (0.17±0.03 vs. 0.05±0.01, P<0.001) excretion when compared with breast feeding. There was higher excretion of calcium and sodium in patients under 3 kg. Children with familial antecedents presented some differences in urinary excretion, with higher uric acid (1.50±0.30 vs. 0.80±0.08, P<0.05) but lower calcium (0.05±0.02 vs. 0.10±0.01, P<0.05) and sodium (0.15±0.02 vs. 0.20±0.02, P<0.05) excretion, respectively. This report provides urinary parameters obtained in healthy newborns and correlates them with factors that could be involved in the genesis of osteopenia, renal stones, and/or nephrocalcinosis. Received: 8 May 2000 / Revised: 7 June 2001 / Accepted: 12 June 2001     

CCL2/MCP‐1 and CXCL12/SDF‐1 blockade by L‐aptamers improve pancreatic islet engraftment and survival in mouse

The blockade of pro‐inflammatory mediators is a successful approach to improve the engraftment after islet transplantation. L‐aptamers are chemically synthesized, nonimmunogenic bio‐stable oligonucleotides that bind and inhibit target molecules conceptually similar to antibodies. We aimed to evaluate if blockade‐aptamer‐based inhibitors of C‐C Motif Chemokine Ligand 2/monocyte chemoattractant protein‐1 (CCL2/MCP‐1) and C‐X‐C Motif Chemokine Ligand 12/stromal cell‐derived factor‐1 (CXCL12/SDF‐1) are able to favor islet survival in mouse models for islet transplantation and for type 1 diabetes. We evaluated the efficacy of the CCL2‐specific mNOX‐E36 and the CXCL12‐specific NOX‐A12 on islet survival in a syngeneic mouse model of intraportal islet transplantation and in a multiple low doses of streptozotocin (MLD‐STZ) diabetes induction model. Moreover, we characterized intrahepatic infiltrated leukocytes by flow cytometry before and 3 days after islet infusion in presence or absence of these inhibitors. The administration for 14 days of mNOX‐E36 and NOX‐A12 significantly improved islet engraftment, either compound alone or in combination. Intrahepatic islet transplantation recruited CD45⁺ leucocytes and more specifically CD45+/CD11b+ mono/macrophages; mNOX‐E36 and NOX‐A12 treatments significantly decreased the recruitment of inflammatory monocytes, CD11b⁺/Ly6C^high/CCR2⁺ and CD11b⁺/Ly6C^high/CXCR4⁺ cells, respectively. Additionally, both L‐aptamers significantly attenuated diabetes progression in the MLD‐STZ model. In conclusion, CCL2/MCP‐1 and CXCL12/SDF‐1 blockade by L‐aptamers is an efficient strategy to improve islet engraftment and survival.     

Microvascular Damage in Type 1 Diabetic Patients Is Reversed in the First Year After Simultaneous Pancreas–Kidney Transplantation

Simultaneous pancreas–kidney transplantation (SPK) is an advanced treatment option for type 1 diabetes mellitus (DM) patients with microvascular disease including nephropathy. Sidestreamdarkfield (SDF) imaging has emerged as a noninvasive tool to visualize the human microcirculation. This study assessed the effect of SPK in diabetic nephropathy (DN) patients on microvascular alterations using SDF and correlated this with markers for endothelial dysfunction. Microvascular morphology was visualized using SDF of the oral mucosa in DN (n = 26) and SPK patients (n = 38), healthy controls (n = 20), DM1 patients (n = 15, DM ≥ 40 mL/min) and DN patients with a kidney transplant (KTx, n = 15). Furthermore, 21 DN patients were studied longitudinally up to 12 months after SPK. Circulating levels of angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2) and soluble thrombomodulin (sTM) were measured using ELISA. Capillary tortuosity in the DN (1.83 ± 0.42) and DM ≥ 40 mL/min (1.55 ± 0.1) group was increased and showed reversal after SPK (1.31 ± 0.3, p < 0.001), but not after KTx (1.64 ± 0.1). sTM levels were increased in DN patients and reduced in SPK and KTx recipients (p < 0.05), while the Ang‐2/Ang‐1 ratio was normalized after SPK and not after KTx alone (from 0.16 ± 0.04 to 0.08 ± 0.02, p < 0.05). Interestingly, in the longitudinal study, reversal of capillary tortuosity and decrease in Ang‐2/Ang‐1 ratio and sTM was observed within 12 months after SPK. SPK is effective in reversing the systemic microvascular structural abnormalities in DN patients in the first year after transplantation.     

Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single‐center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r‐ATG/EVR, n = 88), or mycophenolate (r‐ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy‐proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06–0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r‐ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r‐ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).     

Comparison of curative effects between mammotome‐assisted minimally invasive resection (MAMIR) and traditional open surgery for gynecomastia in Chinese patients: A prospective clinical study

To analyze and compare prospectively the curative effects between mammotome‐assisted minimally invasive resection (MAMIR) and traditional open surgery (TOS) for gynecomastia in Chinese male patients, a total of 60 patients suffering from grade I and II gynecomastia, evaluated by automated whole‐breast ultrasound (AWBU), were recruited and randomly divided into TOS and MAMIR groups (each n = 30). The postoperative scar size, healing time, patient hospital stay, postoperative satisfaction, postoperative pain, and complications including edema and bruising were analyzed. The participants were followed up for 1 week, 1 month, 6 months, and 1 year after surgery. Compared with patients who received TOS, patients in the MAMIR group had significantly smaller scar sizes (0.40 ± 0.08 cm vs 5.34 ± 0.38 cm, P < 0.01), shorter healing times (3.67 ± 0.71 days vs 7.90 ± 0.92 days, P < 0.01), and hospitalization (2.60 ± 0.62 vs 7.17 ± 0.83 days, P < 0.01), as well as higher postoperative satisfaction (4.70 ± 0.60 vs 3.20 ± 0.55 scores, P < 0.01), respectively. Patients in the MAMIR group experienced postoperative mild pain significantly more often than those in the TOS group (6.70 ± 1.06 vs 4.13 ± 0.78 scores, P < 0.01, respectively), but with significantly less postoperative severe pain (53.33% vs 0.00%, P < 0.000). While the incidence rate of edema and bruises was significantly higher in the MAMIR group compared with the TOS group (47% vs 17%, P = 0.013 and 54% vs 20%, P = 0.007, respectively). MAMIR had advantages for curative effects compared with traditional open surgery. However, the recurrence rate in patients needs to be further studied.     

Clinical and economic burden of infections in hospitalized solid organ transplant recipients compared with the general population in Canada – a retrospective cohort study

Infections continue to be a major cause of post‐transplant morbidity and mortality, requiring increased health services utilization. Estimates on the magnitude of this impact are relatively unknown. Using national administrative databases, we compared mortality, acute care health services utilization, and costs in solid organ transplant (SOT) recipients to nontransplant patients using a retrospective cohort of hospitalizations in Canada (excluding Manitoba/Quebec) between April‐2009 and March‐2014, with a diagnosis of pneumonia, urinary tract infection (UTI), or sepsis. Costs were analyzed using multivariable linear regression. We examined 816 324 admissions in total: 408 352 pneumonia; 328 066 UTI's; and 128 275 sepsis. Unadjusted mean costs were greater in SOT compared to non‐SOT patients with pneumonia [(C$14 923 ± C$29 147) vs. (C$11 274 ± C$18 284)] and sepsis [(C$23 434 ± C$39 685) vs. (C$20 849 ± C$36 257)]. Mortality (7.6% vs. 12.5%; P < 0.001), long‐term care transfer (5.3% vs. 16.5%; P < 0.001), and mean length of stay (11.0 ± 17.7 days vs. 13.1 ± 24.9 days; P < 0.001) were lower in SOT. More SOT patients could be discharged home (63.2% vs. 44.3%; P < 0.001), but required more specialized care (23.5% vs. 16.1%; P < 0.001). Adjusting for age and comorbidities, hospitalization costs for SOT patients were 10% (95% CI: 8–12%) lower compared to non‐SOT patients. Increased absolute hospitalization costs for these infections are tempered by lower adjusted costs and favorable clinical outcomes.     

Short‐term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3‐month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3‐months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24‐months and allograft histology score at 12‐month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24‐months posttransplant, and at last follow‐up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12‐months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor‐specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long‐term implications for kidney allograft function.     

Hypothermic continuous machine perfusion improves metabolic preservation and functional recovery in heart grafts

The number of heart transplants is decreasing due to organ shortage, yet the donor pool could be enlarged by improving graft preservation. Hypothermic machine perfusion (MP) has been shown to improve kidney, liver, or lung graft preservation. Sixteen pig hearts were recovered following cardioplegia and randomized to two different groups of 4‐hour preservation using either static cold storage (CS) or MP (Modified LifePort© System, Organ Recovery Systems©, Itasca, Il). The grafts then underwent reperfusion on a Langendorff for 60 min. Energetic metabolism was quantified at baseline, postpreservation, and postreperfusion by measuring lactate and high‐energy phosphates. The contractility index (CI) was assessed both in vivo prior to cardioplegia and during reperfusion. Following reperfusion, the hearts preserved using CS exhibited higher lactate levels (56.63 ± 23.57 vs. 11.25 ± 3.92 μmol/g; P < 0.001), increased adenosine monophosphate/adenosine triphosphate (AMP/ATP) ratio (0.4 ± 0.23 vs. 0.04 ± 0.04; P < 0.001), and lower phosphocreatine/creatine (PCr/Cr) ratio (33.5 ± 12.6 vs. 55.3 ± 5.8; P <0.001). Coronary flow was similar in both groups during reperfusion (107 ± 9 vs. 125 + /‐9 ml/100 g/min heart; P = ns). CI decreased in the CS group, yet being well‐preserved in the MP group. Compared with CS, MP resulted in improved preservation of the energy state and more successful functional recovery of heart graft.     

Effects of buffering in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were exposed to extreme hypercapnia (Paco_2-20 kPa) at Fio₂ 0.4 for 480 min, with (n = 6) or without (n = 6) continuous infusion of isotonic buffers (bicarbonate and trometamol). Arterial pH was higher in buffered animals than controls, 7.21 ±0.01 vs 7.01±0.01 (mean ± s.e.mean, P < 0.01). Serum osmolality and Paco₂ did not differ between groups throughout the experiment. The hemodynamic response to hypercapnia was attenuated in the buffered group, who had lower heart rate, 133 ± 6 vs 189±12 min^-1 (P < 0.01), mean arterial pressure (MAP) 109 ± 4 vs 124 ± 4 mmHg (14.5 ± 0.5 vs 16.5 ± 0.5 kPa) (P < 0.05), mean pulmonary arterial pressure 16±1 vs 23 ± 1 mmHg (2.1 ±0.1 vs 3.1 ±0.1 kPa) (P < 0.01), and pulmonary vascular resistance (PVR) 249 ± 21 vs 343 ± 20 dyn s-cm^-5 (2490±210 vs 3430±200 μN-s-cm^-5) (P < 0.01), compared with the control group. Subsequently, both groups were exposed to hypercapnic hypoxemia by stepwise increases in Fio₂ (0.15, 0.10, 0.05) at 30-min intervals, while Fico₂ was kept at 0.2. PVR increased in both groups (P < 0.05) but, except for heart rate, all hemodynamic differences between the groups disappeared during hypoxia. At Fio₂ 0.15, buffered animals had higher arterial oxygen saturation (73 ± 5%) than the controls (55 ± 5%), (P < 0.05). The control animals died after 1–29 min (mean 14 min) at Fio₂ 0.10, while all buffered animals survived Fio₂ 0.10 with stable MAP (122 ± 14 mmHg (16.3 ± 1.9 kPa). The buffered animals died after 4–22 min (mean 15 min) at Fio₂ 0.05. We conclude that buffering to a pH of 7.21 attenuates the observed hemodynamic response in extreme hypercapnia and improves survival in hypercapnic hypoxemia.     

CSA/AZA,in the absence of prednisone,improves linear growth in renal transplanted children

We compared the results of 44 renal transplants in children, of whom 24 were treated with CSA/AZA and 20 with prednisone in combination with AZA and/or CSA. There were no differences in age distribution or mean ages at transplant between the two treatment groups. The CSA/AZA group had a longer follow-up (29 ± 33 vs 17 ± 18 months). At the last follow-up, five children in the CSA/AZA and none in the prednisone group had lost their grafts. Serum creatinine increased in both groups from 0.7 ± 0.1 mg/dl and 0.9 ± 0.1 mg/dl at the end of the first month to 1.1 ± 0.2 mg/dl in the 36th month (CSA/AZA group) (P < 0.0001) and to 1.5 ±0.6 mg/dl in the 18th month (prednisone group) (P < 0.05), respectively. Total cholesterol level was 189 ± 52 mg/dl and 178 ± 60 mg/dl and LDL level was 117 ± 48 mg/dl and 115 ± 51 mg/dl for the prednisone and CSA/AZA groups, respectively. HDL was greater in the CSA/AZA group (50 ± 10 vs 41 ± 10 mg/dl) (P < 0.03), and VLDL was greater in the prednisone group (31 ± 13 vs 22 ± 8 mg/dl) (P < 0.05). Serum triglyceride was greater in the prednisone group (174 ± 93 vs 112 ± 50 mg/dl) (P < 0.03). The standard deviation score for height of the children in the prednisone group did not change (? 2.4 ± 1.4 vs ? 2.1 ± 1.4 SDS), whereas the SDS height score for the CSA/AZA children increased from ? 3.1 ± 1.7 to ? 2.6 ± 1.5, ? 1.9 ± 1.4 and ? 1.7 ± 1.4, at 12, 24 and 36 months, respectively (P < 0.001). CSA/AZA is a good immunosuppressive regime for the first renal transplant in children, but only 75 % tolerated AZA/CSA without same damage to their grafts.     

Mental health condition of caregivers affected metal health of burn injury patients

The present study aimed to explore the association between mental health condition of caregivers and mental health of burn injury patients. Totally 300 burn injury patients and 300 caregivers were enrolled. These two cohorts of patients were randomly allocated to study group and control group (150 patients and 150 caregivers in each group). The mental health condition of patients and caregivers was evaluated both before and after psychological interventions. There was a significant reduction of the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) of patients in the study group and control group after intervention (28.23 ± 4.98 vs 32.21 ± 5.01, P < 0.001; 28.18 ± 5.01 vs 31.18 ± 5.04, P < 0.001). The corresponding indexes of caregivers showed similar results before (SDS: 47.03 ± 4.41 vs 46.98 ± 4.39, P = 0.922; SAS: 47.01 ± 4.31 vs 46.93 ± 4.35, P = 0.873) and after intervention (21.76 ± 4.23 vs 38.98 ± 4.09, P < 0.001; SAS: 21.02 ± 4.09 vs 38.65 ± 4.04, P < 0.001). The SDS score of patients in study group was positively correlated with the SDS and SAS score of caregivers (r = 0.418 and 0.218, P = 0.003 and 0.012). The SAS score of patients in the study group was also positively correlated with the SDS and SAS scores of caregivers (r = 0.107 and 0.761, P = 0.029 and 0.018). Multiple linear regression showed that age, education and time of care per day were the independent variables associated with mental health condition of caregivers in the study group (P < 0.05). Mental health condition of caregivers was closely related to the mental health of patients. Age, education and time of care per day were the independent variables associated with mental health condition of caregivers.     

Minimally Invasive Kidney Transplantation Had Better Cosmetic Effect and Comparable Safety: A Randomized Controlled Trial

PurposeTo prospectively evaluate short-term outcomes between a novel minimally invasive kidney transplantation (MIKT) technique and conventional kidney transplantation (CKT).Materials and MethodsFrom March 2018 to February 29, 2019, 148 patients were randomized into MIKT and CKT groups. All patients were followed up for 12 months.ResultsThe MIKT group had a significantly shorter incision length (5.6 ± 0.4 vs 11.4 ± 0.4 cm, P < .001). There was no difference in operation time, blood loss, acute rejection, infection, and wound dehiscence between MIKT and CKT groups. Both groups had comparable pain scores and analgesic requirements in the first 3 days after transplantation and comparable renal function at 12 months. The MIKT group had higher satisfaction than the CKT group during follow-up (9.3 ± 0.3 vs 8.1 ± 0.5, P < .001; 9.5 ± 0.2 vs 8.5 ± 0.3, P < .001; 9.4 ± 0.3 vs 8.5 ± 0.3, P < .001; 9.2 ± 0.3 vs 8.5 ± 0.4, P = .003 for posttransplant months 1, 3, 6, and 12, respectively). The MIKT group had a significantly lower Vancouver Scar Scale score (4.1 ± 0.4 vs 5.2 ± 0.5, P < .001; 4.3 ± 0.4 vs 6.1 ± 0.4, P < .001; 5.2 ± 0.6 vs 6.7 ± 0.5, P < .001; 7.7 ± 0.7 vs 8.9 ± 0.5, P = .009 for posttransplant months 1, 3, 6, and 12, respectively).ConclusionsMIKT has demonstrated equivalent safety and improved patient satisfaction compared to CKT. This technique may be an appropriate choice for selected patients.     

The Effect of Cardiopulmonary Bypass and Hypothermic Circulatory Arrest on Hepatic Histology in Newborn Animals: An Experimental Study

Still little is known about the effect of cardiac surgery on neonatal hepatic tissue. We examined the effect of cardiopulmonary bypass (CPB) and the effect of deep hypothermic circulatory arrest (DHCA) on neonatal hepatic tissue. Liver biopsies of neonatal piglets were taken after CPB (n = 4), after DHCA (n = 5), and after surgery without CPB (non‐CPB; n = 3). Additionally, findings were compared to those of control piglets (n = 9). The liver specimens were fixed, stained with hematoxylin and eosin, and scored regarding inflammatory reaction, hepatocellular edema, and apoptosis. Inflammation score of treated groups was higher than in control; CPB 2.5 ± 0.5, DHCA 1.6 ± 0.4, non‐CPB 1.2 ± 0.6, control 0.4 ± 0.3 (P < 0.001 CPB and DHCA vs. control; P < 0.05 non‐CPB vs. control). Hepatic cell edema was more evident after DHCA (score 2.0 ± 0.4 vs. 0.2 ± 0.3 in control and 0.6 ± 0.5 after CPB; P < 0.001 and P < 0.05, respectively). The highest apoptotic cell count was in the non‐CPB group (22.3 ± 6.3 vs. 11.4 ± 3.6 in control and 8.9 ± 5.4 after CPB; P < 0.05). The present study showed that (i) surgical trauma induces hepatic cell apoptosis; (ii) CPB increases hepatic inflammatory reaction; and (iii) DHCA amplifies hepatic cell edema.     

SDF‐1/CXCR4 Axis in Tie2‐Lineage Cells Including Endothelial Progenitor Cells Contributes to Bone Fracture Healing

CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal‐derived‐factor 1 (SDF‐1). SDF‐1/CXCR4 interaction is reported to play an important role in vascular development. On the other hand, the therapeutic potential of endothelial progenitor cells (EPCs) in fracture healing has been demonstrated with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis enhancement at sites of fracture. The purpose of this study was to investigate the influence of the SDF‐1/CXCR4 pathway in Tie2‐lineage cells (including EPCs) in bone formation. We created CXCR4 gene conditional knockout mice using the Cre/loxP system and set two groups of mice: Tie2‐Cre^ER CXCR4 knockout mice (CXCR4^?/?) and wild‐type mice (WT). We report here that in vitro, EPCs derived from of CXCR4^?/? mouse bone marrow demonstrated severe reduction of migration activity and EPC colony‐forming activity when compared with those derived from WT mouse bone marrow. In vivo, radiological and morphological examinations showed fracture healing delayed in the CXCR4^?/? group and the relative callus area at weeks 2 and 3 was significantly smaller in CXCR4^?/? group mice. Quantitative analysis of capillary density at perifracture sites also showed a significant decrease in the CXCR4^?/? group. Especially, CXCR4^?/?group mice demonstrated significant early reduction of blood flow recovery at fracture sites compared with the WT group in laser Doppler perfusion imaging analysis. Real‐time RT‐PCR analysis showed that the gene expressions of angiogenic markers (CD31, VE‐cadherin, vascular endothelial growth factor [VEGF]) and osteogenic markers (osteocalcin, collagen 1A1, bone morphogenetic protein 2 [BMP2]) were lower in the CXCR4^?/? group. In the gain‐of‐function study, the fracture in the SDF‐1 intraperitoneally injected WT group healed significantly faster with enough callus formation compared with the SDF‐1 injected CXCR4^?/? group. We demonstrated that an EPC SDF‐1/CXCR4 axis plays an important role in bone fracture healing using Tie2‐Cre^ER CXCR4 conditional knockout mice. © 2014 American Society for Bone and Mineral Research.