In vitro vasoactive effects of dexmedetomidine on isolated human umbilical arteries.

OBJECTIVE: We aimed to investigate the vasoactive effects of dexmedetomidine on isolated human umbilical arteries and possible mechanisms involved. METHODS: Human umbilical artery strips were suspended in Krebs-Henseleit solution and dose-response curves were obtained for cumulative dexmedetomidine before and after incubation with different agents; propranolol, atropine, yohimbine, prazosin, indomethacin, verapamil. Effects of calcium on cumulative dexmedetomidine-induced contractions were also studied. RESULTS: Cumulative dexmedetomidine resulted in dose dependent contraction responses. Incubation with propranolol (Emax: 93.3 ± 3.26 %), atropine (Emax: 92.0 ± 6.54 %), or indomethacin (Emax: 94.25 ± 2.62 %), did not attenuate dexmedetomidine-elicited contractions (p > 0.05). There were significant decreases in the contraction responses of cumulative dexmedetomidine with yohimbine (Emax: 12.1 ± 11.9 %), prazosin (Emax: 28.8 ± 4.6 %) and verapamil (Emax: 11.2 ± 13.6 %) (p < 0.05). In Ca+2 free medium contraction responses to cumulative dexmedetomidine was insignificant (Emax: 5.20 ± 3.42 %). Addition of cumulative calcium to the Ca+2 free medium resulted in concentration dependent increase in contractions (Emax: 64.83 ± 37.7 %) (p < 0.05). CONCLUSION: Dexmedetomidine induces vasoconstriction in endothelial-free umbilical arteries via both, α1- and α2-adrenergic receptors and also extracellular Ca+2 concentrations play a major role. ß-adrenergic receptors, muscarinic cholinergic receptors, and inhibition of cyclooxygenase enzyme are not involved in this vasoconstriction (Fig. 3, Ref. 36).

The correlation between electrocardiographic parameters and mortality in non-cardiac ICU patients.

OBJECTIVE: This study aimed to determine the correlation between selected electrocardiogram (ECG) parameters (recorded at admission) and mortality in non-cardiac, non-COVID-19 intensive care unit (ICU) patients, and to determine the sensitivity and specificity of a novel admission ECG score (AD-ECG) for predicting mortality. Additionally, the sensitivity and specificity of the AD-ECG and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores for predicting ICU mortality were compared. PATIENTS AND METHODS: Clinical and laboratory data, and ECG parameters were compared between ICU survivors and non-survivors. ECG parameters (the QTc and Tpe intervals, and the Tpe/QT and Tpe/QTc ratios) and pulse pressure at ICU admission (baseline) were used to calculate the AD-ECG score. Cut-off values for ECG parameters, pulse pressure, and AD-ECG and APACHE II scores were calculated. The sensitivity and specificity of the APACHE II and AD-ECG scores were determined. RESULTS: The study included 167 patients. Mortality was higher in the patients with comorbidities, mechanical ventilation, and length of ICU stay (p < 0.05). The QTc and Tpe intervals, and the TPe/QT and TPe/QTc ratios differed significantly between the survivors and non-survivors (p < 0.05). The sensitivity and specificity of the AD-ECG score were similar to those of the APACHE II score. When pulse pressure, and the QTc and Tpe intervals were added to APACHE II, the sensitivity of the APACHE II score increased from 78.9% to 85.5%, and its specificity increased from 75% to 86.8%. CONCLUSIONS: A novel admission ECG score (AD-ECG) based on ECG parameters (the QTc and Tpe intervals, and the Tpe/QT and Tpe/QTc ratios) and pulse pressure has similar sensitivity and specificity as the APACHE II score for predicting non-cardiac ICU mortality. Adding pulse pressure, and the QTc and Tpe intervals increases the sensitivity and specificity of the APACHE II score; however, as the present study included non-cardiac patients only, additional larger-scale studies are needed to obtain more precise results.

Reversible post-pregabalin peripheral edema in a spinal cord injury patient.

STUDY DESIGN: Case report. OBJECTIVES: To report a case of paraplegia with limb edema caused by pregabalin. SETTING: Turkish Armed Forces Rehabilitation Center, Ankara, Turkey. CASE REPORT: A 40-year-old male patient with T11 paraplegia had the complaint of swelling in both the lower limbs. He had been given pregabalin because of the neuropathic pain in both the lower limbs. At 10 months, the patient has experienced edema in lower limbs. There was severe edema in both legs, ankles and feet, more evident on the left. Venous Doppler ultrasound was normal on both sides. Blood tests for possible etiologies were normal. No other etiology could be found. The edema was considered to be caused by pregabalin and the medicine was ceased gradually. The edema resolved completely in 2 weeks. CONCLUSION: Pregabalin, which is one of medications used for neuropathic pain, might cause limb edema, that is, a condition needs differential diagnosis. This is particularly important for patients with spinal cord injuries (SCIs). Such adverse effect of pregabalin should be kept in mind as an etiology of limb edema in SCI management.

Effects of artemisinin and hydroxychloroquine on cytokines in experimental sepsis.

Pro-and anti-inflammatory cytokines mediate the inflammatory response in sepsis. Therefore, regulation of cytokines with medications in risky situations may protect the patients from sepsis. Hydroxychloroquine and artemisinin are antimalarial drugs with immunomodulatory properties. In this study, we intended to investigate the effects of artemisinin and hydroxychloroquine on the cytokines released during sepsis in the rat model. Twenty-four rats were randomized into four groups. The control group received oral saline, the sepsis group received oral saline and intraperitoneal lipopolysaccharide toxin (LPS), the artemisinin-treated sepsis group received oral 33.33 mg/kg of artemisinin, and the hydroxychloroquinetreated sepsis group received oral 33.33 mg/kg of hydroxychloroquine before LPS injection. Three hours later, serum cytokines were measured. An increase was detected in TNF-a, IL-1, and IL-6 levels in the sepsis group compared to the control (p<0.01). Oral pretreatment with artemisinin resulted in significant downregulation only of IL-1 levels (p<0.01). Cytokines IL-1 and IL-6 were significantly downregulated in the serum of LPS-induced rats pretreated with oral hydroxychloroquine than rats with sepsis (p<0.01). Decreases observed in TNF-a and IL-10 levels were insignificant. These results demonstrated that both artemisinin and hydroxychloroquine attenuate the release of pro-inflammatory cytokines three hours after LPS-induced sepsis in rats. A significant decrease was observed in serum IL-1 and IL-6 levels with hydroxychloroquine and IL-1 levels with artemisinin. Based on our findings, we suggest that the therapeutic potential of artemisinin and hydroxychloroquine may be beneficial in preventing cytokine storm during sepsis, and further research is needed to determine the optimal timing of administration.

Evaluation of personalized methylprednisolone therapy in critically ill COVID-19 patients: an observational comparative study using real-life data.

OBJECTIVE: Methylprednisolone is commonly used to attenuate the cytokine storm and prevent mortality in COVID-19 pneumonia. However, the optimal methylprednisolone dose and duration are unclear. Additional data are required on the effectiveness of methylprednisolone in reducing mortality in COVID-19. This real-life retrospective study aimed to analyze the data of a COVID-19 dedicated ICU and compare the mortality rates of standard care, low-dose, and pulse-dose methylprednisolone in patients requiring mechanical ventilatory support. PATIENTS AND METHODS: Methylprednisolone's indication, dose, and duration were determined according to the severity of COVID-19 pneumonia based on the patient's demographic parameters, comorbidities, laboratory data, radiology, and arterial blood gas analysis results. 867 patients were grouped as: no methylprednisolone (standard care), low-dose (0.5-1 mg/kg/day) methylprednisolone or pulse-dose (250-1,000 mg/day) methylprednisolone. RESULTS: The overall mortality rate was 63.78%. Adjusting the dose of methylprednisolone according to the severity of the disease resulted in statistically similar mortality rates despite the increase in disease severity. Mortality was 62.71% in standard treatment, 65.76% in low-dose, and 62.10% in pulse-dose methylprednisolone groups (p = 0.633). Invasive mechanical ventilation at admission was associated with increased mortality (HR: 1.826 [95% CI: 1.542-2.161]; p < 0.001). Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were also associated with mortality. CONCLUSIONS: Personalizing the dose and duration of methylprednisolone according to the patient's disease severity assessed with demographic, clinical, and laboratory results may benefit mortality in severe COVID-19 patients receiving ventilatory support in the ICU. Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were associated with mortality in our patient cohort.

Idiopathic intracranial hypertension - a wider spectrum than headaches and blurred vision.

BACKGROUND: The purpose of this study was to analyse less known clinical scenarios associated with idiopathic intracranial hypertension. METHODS: The study involved analysis of magnetic resonance imaging signs of idiopathic intracranial hypertension in patients with spontaneous rhinoliquorrhoea (n = 7), in patients with temporal lobe epilepsy and surgically treated antero-inferior temporal lobe meningo-encephaloceles (n = 15), and in patients who developed clinical signs of idiopathic intracranial hypertension following the treatment of spontaneous intracranial hypotension (n = 7). RESULTS: Three of six patients with spontaneous rhinoliquorrhoea and six of 15 operated patients with temporal lobe epilepsy due to temporal lobe meningo-encephaloceles showed magnetic resonance imaging signs of idiopathic intracranial hypertension and had a body mass index >30 kg/m2. Rebound high pressure headaches and sings of idiopathic intracranial hypertension occurred in seven of 44 surgically treated spontaneous intracranial hypotension patients. CONCLUSIONS: Magnetic resonance imaging findings should guide the clinician to consider (idiopathic) intracranial hypertension when patients develop spontaneous rhinoliquorrhoea, temporal lobe epilepsy secondary to temporal lobe meningoencephaloceles or high pressure headaches in spontaneous intracranial hypotension. Whether idiopathic intracranial hypertension must be regarded as a differential diagnosis or as a cause, or whether there are common pathophysiological pathways that lead to signs of idiopathic intracranial hypertension in this wider spectrum of disease is the focus of further study.

High-Resolution Gadolinium-Enhanced MR Cisternography Using Compressed-Sensing T1 SPACE Technique for Detection of Intracranial CSF Leaks.

In patients with CSF rhinorrhea, accurate identification of the CSF leakage site is crucial for surgical planning. We describe the application of a novel gadolinium-enhanced high-resolution 3D compressed-sensing T1 SPACE technique for MR cisternography and compare findings with CT cisternography and intraoperative results. In our pilot experience with 7 patients, precise detection of CSF leaks was feasible using compressed-sensing T1 SPACE, which appeared to be superior to CT cisternography.

Treatment of lateral epicondilitis using three different local injection modalities: a randomized prospective clinical trial.

BACKGROUND: To determine the effectiveness of three different local injection modalities in the treatment of lateral epicondilitis. METHODS: In a prospective randomized study on lateral epicondilitis, 75 patients were divided into three equal groups A, B and C (n = 25) and were treated using three different method of local injection. The patients in group A were treated with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine), those in group B were treated with injection of local anaesthetic (1 mL lidocaine) combined with peppering technique and those in group C with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine) and peppering technique. The outcome was defined by measuring the elbow pain during the activity using a 10-cm visual analogue scale (VAS) and satisfaction with the treatment using a scoring system based on the criteria of the Verhaar et al. at 3 weeks and 6 months after the injection and compared with the pre-treatment condition. RESULTS: There were significant (P = 0.006) differences in the successful outcomes between the three groups at 6 months. In group C in which local steroid + peppering injection technique were used; excellent results were obtained in 84% of patients comparing to 36% and 48% for patients in groups A and B, respectively. The successful outcomes were statistically higher in group C comparing to group A (P = 0.002) and group B (P = 0.011). In all groups, there was a significantly lower pain (VAS) at the 3-week and 6-month follow-ups comparing to the pre-treatment condition. VAS measured at 6-month follow-up were significantly lower in group C comparing to other groups (P = 0.002). CONCLUSION: In the treatment of lateral epicondilitis, combination of corticosteroid injections with peppering is more effective than corticosteroid injections or peppering injections alone and produces better clinical results.

Evaluation of Ureteral Stent Colonization in Live-Donor Renal Transplant Recipients.

BACKGROUND: Ureteral stent insertion during kidney transplantation is a matter of debate. Stenting has been proven to reduce the risk of surgical complications. In addition, it has been reported to increase risks such as urinary tract infections especially after operation. Ureteral stent colonization (USC) is known to play a role in the pathogenesis of stent related-infections. The aim of this study was (1) to assess the frequency of USC and values of urine cultures in identifying colonizing bacteria; (2) to assess the importance of indwelling time for USC in live-donor renal transplant recipients; and (3) to evaluate the biomarker role of neutrophil-to-lymphocyte ratio (NLR) on USC. METHODS: A total of 107 live-donor kidney transplant patients were included in the study (76 men and 31 women). The mean age was 43.7 years, and average indwelling time of the ureteral stent was 24.7 days. Patients were divided into three groups according to indwelling stent time as group 1: 15 to 21 days (3rd week), group 2: 22 to 28 days (4th week), and group 3: 29 to 35 days (5th week). The decision to remove the stent was primarily based on clinical judgment. Ureteral stents were removed with the use of flexible cystoscopy. Midstream urine for urine culture and blood samples for NLR were taken prior to stent removal. The removed stents were divided into three parts and taken for bacteriological investigation. RESULTS: Of 107 patients, USC was detected in 24 (22.4%) patients, whereas urinary proliferation was observed in 8 (7.4%) patients. The most common microorganisms found in USC was the Enterecoccus species. The most common microorganisms in urinary culture were Enterecoccus spp. and Klebsiella pnemoniae. All patients with isolated microorganisms in the urine had USC (P < .001). On the other hand, proliferation in urinary culture was observed only in 30% of patients. Urine culture was not significant in identification of USC (P = .063). The three patient groups that were determined according to indwelling stent time were compared in terms of USC, proliferation in urine culture, and NLR. The highest incidence of USC was found in group 3 (44%) and the least in group 2 (11%) (P < .05). No significant difference was found between the groups in terms of urine culture (P = .546). Although no significant difference was found between groups 1 and 2 in NLR values (P = .755), NLR was significantly higher in group 3 (P = .026). CONCLUSIONS: Colonization is common in ureteral stents inserted in live-donor kidney transplant patients, although routine urine culture is insufficient in identfying this colonization. The most common microorganism detected in ureteral stent colonization was Enterecoccus spp. The 4th week was the most convenient time for stent removal time in terms of USC among the 3rd, 4th, and 5th weeks. In addition, increased NLR might have value as a biomarker for USC.

Comparision of Ureteral Stent Colonization Between Deceased and Live Donor Renal Transplant Recipients.

BACKGROUND: The use of a ureteral stent can cause a urinary tract infection (UTI), although it reduces urologic complications. UTIs are associated with a higher rate of ureteral stent colonization (USC). The aim of this study was to compare USC in living and deceased donor renal transplant recipients. MATERIAL AND METHODS: We conducted a prospective study of 48 patients who underwent renal transplantation between January and December 2016. The stents were removed aseptically, the inner surface of proximal and distal ends of stents were irrigated with liquid culture medium, and then they were vortexed for bacteriological investigation. Urine cultures were taken at the same time. RESULTS: A total of 45 renal transplantation patients (21 from cadavers, 24 from live donors) were evaluated in the study. The duration time of stent retention in patients with live donors was 25.04 ± 4.55 and in patients with deceased donors was 26.19 ± 4.08 days (P = .376). USC was observed in 12 (57.1%) and 6 (25%) patients while positive urine culture (PUC) was detected in 5 (23.8%) and 2 (8.3%) patients in deceased and live donor transplant recipients, respectively. Although the USC rate was significantly higher in the deceased donor renal transplant group (P = .022), there was no significant different in the rates of PUC (P = .137). Enterecoccus species was the common pathogen isolated from ureteral stent and urine. The micro-organisms isolated from ureteral stent in deceased and live donors, respectively, were distributed as follows: Enterococcus 5/3, Candida 3/1, Escherichia coli 2/1, Klebsiella pneumonia 1/1, and staphylococci in 1/0 patients. All E coli and K pneumoniae are extended spectrum beta-lactamase (ESBL)-positive isolates and resistant to sulfamethoxazole-trimethoprim (SMX/TMP). CONCLUSIONS: We report a high incidence of USC in deceased renal transplants. Enterecoccus instead of E coli is the most common pathogen during the first month after transplantation. Transplantation centers should be aware that deceased donor renal transplant recipients are more prone to stent-related infection and the antibacterial resistance rapidly increases in uropathogens.

Results of Real-time Multiplex Polymerase Chain Reaction Assay in Renal Transplant Recipients With Sterile Pyuria.

Urinary tract infections are a major cause of morbidity and hospitalization after renal transplantation. Patients treated with immunosuppressive drugs suffer not only from common uropathogens but also from opportunistic infections caused by unusual uropathogens. Sterile pyuria is associated with numerous infectious agents including viruses, fungi, and atypical or fastidious organisms. The objective of this study was to investigate the pathogens using real-time multiplex polymerase chain reaction (rtMPCR) assay in sterile pyuria of renal transplant recipients. In this prospective controlled study, pathogen detection was performed with rtMPCR assay on October 2016 in 60 patients with sterile pyuria who had undergone kidney transplantation. A total of 40 renal transplant patients were determined as the control group. Male-to-female ratio was same. The mean age of the subjects with sterile pyuria was 45.7 ± 12.1 (25-74). The mean duration after transplantation was 28.8 ± 3.97 (3-102) months. Pathogens were detected with rtMPCR in 61.7% of sterile pyuria group. This rate was significantly higher compared with the control group (P < .001). Two or more different pathogens were found in 13 (21.7%) patients in sterile pyuria group. The pathogens found included cytomegalovirus in 10 patients (19%), Gardnerella vaginalis and obligate anaerobes in 20 patients (38%), Ureaplasma spp in 17 patients (33%), Candida spp in 2 patients (4%), Mycoplasma hominis in one patient (2%), herpes simplex virus-2 in one patient (2%), and Trichomonas vaginalis in one patient (2%). Sterile pyuria may indicate the presence of genitourinary pathogens that cannot be detected with conventional urine culture method in renal transplantation patients. rtMPCR is an accurate and convenient method for detection of multiple potential pathogens of sterile pyuria in renal transplant patients.

Pregnancy and Delivery in the Sequel of Kidney Transplantation: Single-Center Study of 8 Years' Experience.

BACKGROUND: Depending on hyphothalamic, hyphophyseal, and gonadal axis dysfunction, anovulatory irregular cycles occur and the probability of pregnancy decreases in the patients with chronic kidney disease (CKD). Maternal mortality and morbidity rates are increased in CKD patients; the risk of premature delivery is 70% and the risk of preeclampsia is 40% more than normal among those with a creatine level of >2.5 mg/dL. METHODS: If a pregnancy is expected in the sequel of kidney transplantation (KT), a multidisciplinary team approach should be adopted and both the gynecologist and the nephrologist should follow the patient simultaneously. Among 3883 patients who underwent KT at Antalya Medical Park Hospital Transplantion Department between November 2009 and October 2016, the records of 550 female patients between the ages of 18 and 40 years were examined retrospectively; 31 patients who complied with these criteria were included in the study group. In 6 of these patients who had an unplanned pregnancy, medical abortion was performed after the families were informed about the possible fetal anomalies caused by the use of everolimus in the first trimester, and they were excluded from the study (pregnant group). The control group consisted of 43 patients who had a KT and became pregnant, and of those who had recently undergone KT and shared similarities regarding age, CKD etiology, duration of dialysis, and number of transplants. RESULTS: In both groups, the ages of the patients, their follow-up span and dialysis duration, tissue compatibility, age of the donor, and time elapsed until the pregnancy was analyzed, whereas in the control group, creatinine levels in the first, second, third, and fourth years after the KT were reviewed. Additionally, in the pregnant group, creatinine levels of the first, second, and third trimesters; delivery week; birth weight of the baby; APGAR scores of the first minute; postnatal creatinine levels of first, second, and third years; and prenatal, maternal, and postnatal acute rejections were reviewed. We measured the creatine clearance by use of the Cockcroft-Gault formula in the pregnancy group before pregnancy and during delivery [Cockcroft-Gault formula: (140 - age) × body weight (kg)/72 × plasma creatine level (mg/dL) × 0.85]. CONCLUSIONS: Pregnancy after KT is risky both for the mother and the baby; however, if planned and followed in coordination within an experienced center, both the pregnancy period and the birth process can occur without distress.

Optimal Timing for Removal of the Double-J Stent After Kidney Transplantation.

BACKGROUND: Urologic complications (UC) have gradually decreased in recent years after advanced surgical experience. The incidence of urologic complications varies between 0.22% and 30% in different medical studies. There is no routine usage of double-J stenting (DJS) during renal transplantation (RT) in the literature. It is a necessity, and optimal timing for stent removal is an important question for many transplantation centers. METHODS: This study includes 818 renal transplant patients whose ureteroneocystostomy anastomoses were completed by use of the Lich-Gregorie procedure during a 2-year period at a transplantation center. We performed 926 renal transplantations at Antalya Medical Park Hospital Renal Transplantation Center between January 2014 and January 2016. The patients were divided into four groups according to the timing of DJS removal. RESULTS: For group 1, removal time for DJS was between 5 and 7 days; group 2, Removal time for DJS was between 8 and 14 days; group 3, removal time for DJS was between 15 and 21 days; and group 4, removal time for DJS was later than 22 days. The patients were divided into two groups according to removal time of stent as 5 to 14 days and >15 days. DJS was performed again in the patients whose urine output was reduced during the first 5 days after removal of the DJS, whose creatine level increased, and whose graft ureter and collecting tubules were extended as an ultrasonographic finding. CONCLUSIONS: There is no declared optimal time for the removal of DJS. The removal time was reported between postoperative first week and 3 months in some of the reports of RT centers, according to their protocols. We emphasize that the optimal time for the removal of DJS is 14 to 21 days after RT, based on the findings of our large case report study.

Open, laparoscopic and robot-assisted laparoscopic radical prostatectomy: comparative analysis of operative and pathologic outcomes for three techniques with a single surgeon's experience.

OBJECTIVE: To compare outcomes of open (O-), laparoscopic (L-) and robot-assisted laparoscopic (RAL-) radical prostatectomy (RP) performed by the same surgeon. PATIENTS AND METHODS: From May 1999 to April 2012, 484 RPs were performed by a single surgeon. Patients' data including age, body-mass index, serum prostate specific antigen (PSA) level, Gleason score of prostate biopsy and prostatectomy specimen, preoperative prostate and specimen volumes, clinical and pathologic stages, operation time, estimated blood loss (EBL), catheterization time, blood transfusion rate were recorded. Prospectively collected data was evaluated retrospectively by statistical analyses. RESULTS: Of 484 radical prostatectomies, ORP (50), LRP (308) and RALRP (79) done by the same surgeon were included into study. Mean ages were 63.8, 62.7 and 60.3 years for ORP, LRP and RALRP respectively. Operation times for ORP, LRP and RALRP were 255, 208 and 242 minutes. EBL and hospitalization time were 602, 526, 234 mL, and 9.1, 3.2, 3.2 days for ORP, LRP and RALRP, respectively. While a significant advantage was found for EBL and complication rates in RALRP and for operation time in LRP, significant disadvantages were found in terms of catheterization time, hospitalization time, decrease in hemoglobin and blood transfusion in ORP. However, preoperative prostate volume and serum PSA level, oncologic outcomes and positive surgical margins were nearly similar in all operative techniques. CONCLUSIONS: Minimally invasive techniques such as LRP and RALRP are promising techniques with comparable outcomes with ORP. Shorter catheterization time, less blood loss and fewer complication rates can be provided by RALRP.