Comparison of the ability of short time low PEEP challenge and mini fluid challenge to predict fluid responsiveness in patients undergoing open pancreaticoduodenectomy: an observational cohort study.

OBJECTIVE: The mini-fluid challenge (MFC), which assesses the change in stroke volume index (SVI) following the administration of 100 mL of crystalloids, and the short-time low positive end-expiratory pressure (PEEP) challenge (SLPC), which evaluates the temporary reduction in SVI due to a PEEP increment, are two functional hemodynamic tests used to predict fluid responsiveness in the operating room. However, SLPC has not been assessed in patients undergoing abdominal surgery, and there is no study comparing these two methods during laparotomy. Therefore, we aimed to compare the SLPC and MFC in patients undergoing open pancreaticoduodenectomy. PATIENTS AND METHODS: All patients received a standard hemodynamic management. The study protocol evaluated the percentage change in SVI following the application of an additional 5 cmH2O PEEP (SVIΔ%-SLPC) and the infusion of 100 mL crystalloid (SVIΔ%-MFC). Challenges that resulted in an increase of more than 15% in SVI after the 500 ml of fluid loading were classified as positive challenges (PC). Areas under the receiver operating characteristics curves (ROC AUCs) were used for the comparison of the methods. RESULTS: Thirty-three patients completed the study with 94 challenges. Fifty-five (58.5%) of them were PCs. The ROC AUC of SVIΔ%-MFC was observed to be significantly higher than that of SVIΔ%-SLPC (0.97 vs. 0.64, p < 0.001). The best cut-off value for SVIΔ%-MFC was 5.6%. If we had stopped the bolus fluid administration when SVIΔ%-MFC ≤ 5% was observed (lower limit of the gray zone), we would have postponed the fluid loading in 35 (89.7%) of 39 negative challenges. The amount of fluid deferred would have corresponded to up to 40% of the total fluid given. CONCLUSIONS: SVIΔ%-MFC predicts fluid responsiveness with high diagnostic performance and is better than SVIΔ%-SLPC in patients undergoing open pancreatoduodenectomy. Additionally, the use of SVIΔ%-MFC has the potential to defer up to 40% of the total fluid given. CLINICALTRIALS: gov: NCT05419570.

Convalescent plasma therapy in critically Ill COVID-19 patients: A retrospective cohort study.

Background: Convalescent plasma (CP) therapy can be defined as a passive immunity transfer approach involving the administration of plasma for therapeutic purposes to inpatients hospitalized due to an active virus infection. Passive immunity antibodies can reduce target organ damage and directly neutralize the responsible pathogens. A limited number of studies on the use of CP have reported that critically ill patients can benefit from CP therapy. Aim: We aimed in this study as the outcomes of CP therapy in critically ill coronavirus disease 2019 (COVID-19) patients in intensive care unit (ICU) and determine the differences between the recovery and mortality groups. Patients and Methods: This retrospective design study involved critically ill patients who were diagnosed with COVID-19 pneumonia or who were suspected of having COVID-19 in the ICU between April 1, 2020, and June 1, 2020. Comorbidity of patients, respiratory findings, hemodynamic data, laboratory data, and poor prognostic measures were compared between mortality and recovery group. Results: Convalescent plasma (CP) therapy was supplied for 41 (13.58%) patients in total of 302 COVID-19 patients. Twenty-nine patients were died in total of 41 COVID-19 patients who supplied CP therapy. The mortality rate is 70.73% in CP therapy. There was a significantly higher incidence (P < 0.021) of invasive mechanical ventilation (IMV) and significantly lower mean arterial pressure (MAP) values in mortality group (P < 0.05). There were significantly higher NLR values (P < 0.05), lower platelet count (P < 0.05), lower of glomerular filtration rate (GFR) level (P < 0.05), higher creatinine values (P < 0.05), higher lactate dehydrogenase (LDH) levels (P < 0.05), higher D-dimer levels (P < 0.05), higher level of pro-brain natriuretic peptide (BNP) (P = 0.000), rate of fever (P = 0.031), arrythmia (P = 0.024), and transfusion-associated circulatory overload (TACO) (P = 0.008) were more often in mortality group. Conclusion: Convalescent plasma therapy seems not useful in critically ill COVID-19 patients.

Comparison of the patients with diabetes mellitus using either insulin or oral antidiabetic drug in terms of difficult laryngoscopy: A randomized controlled study.

Aim: We aimed to evaluate the differences in the difficult laryngoscopy as a general anesthetic component in patients with Diabetes Mellitus (DM) using either insulin or oral antidiabetic drug (OADD). Materials and Methods: This study was planned for a total of 230 patients including DM patients and non-DM patients as a control group who would undergo elective surgery between 30.01.2020-30.04.2020. Age, gender, body mass index (BMI), Mallampati scores, thyromental distance (TMD), inter-incisor distance (IID), and neck extension measurements were noted. Preoperative HbA1C levels, DM type, diagnosis time, and duration of insulin or OADD use were recorded. Patients without DM (Group C), patients using insulin (Group I), and patients using OADD (Group D) were separated respectively. Cormack-Lehane (CL) classification of the airway, number of laryngoscopic attempts, intubation success at the first attempt, intubation duration, performance of backward-upward-rightward pressure (BURP) maneuver, and requirement of use of different airway equipment were compared between the groups. Results: The data of 192 patients were compared. The mean IID (mm) was lower in Groups I and D than C. It was the lowest in Group I. Presence of neck extension of more than 30° in Groups I and D was lower than C. Classification of CL in Groups I and D was higher than C. Number of laryngoscopic attempts was higher in Groups I and D than C. Intubation success at the first attempt was lower in Groups I and D than C. The intubation duration was longer in Groups I and D than C. It was the longest in Group I. The more BURP maneuvering was required in Groups I and D than C. In Groups I and D, the number of uses of different airway equipment was higher than in Group C. The rate of using a videolaryngoscope (VL) in Group I was higher than in Groups D and C. Conclusion: Difficult laryngoscopy was more common in DM patients. Moreover, in patients with DM using insulin, VL use was more often and intubation duration was longer than in patients with DM using OADD.

Active breathing control guided stereotactic body ablative radiotherapy for management of liver metastases from colorectal cancer.

Background: Liver metastases may occur during the course of several cancer types and may be associated with significant morbidity and mortality. There is paucity of data regarding the utility of Active Breathing Control (ABC) guided Stereotactic Ablative Body Radiotherapy (SABR) for management of Liver Metastases from Colorectal Cancer (LMCC). Our aim is to investigate the role of ABC guided SABR for management of liver metastases. Patients and methods: 42 liver metastases of 29 patients treated with ABC guided SABR between February 2015 and October 2018 were retrospectively assessed for local control (LC), overall survival (OS), and toxicity outcomes. Primary endpoint was LC. Secondary endpoints were OS and treatment toxicity. Results: At a median follow up duration of 16 months (range: 9-74 months), median OS was 20 months and 3 patients were still alive at last follow up. 1-year OS was 83% and 2-year OS was 28%. LC rates were 92% and 61% at 1 and 2 years, respectively. Comparative analysis of Biological Effective Dose (BED) values revealed that higher BED10 values were associated with higher LC rates (p=0.007). While LC rates for BED10 ≥ 100 Gray (Gy) were 94% and 86% at 1 and 2 years, corresponding LC rates for BED10 < 100 Gy were 89% and 36%, respectively with statistical significance (p=0.007). Assessment of acute and late toxicity outcomes revealed that most common toxicity was fatigue, however, no patients had ≥ grade 3 toxicity. Conclusion: ABC guided SABR is an effective and safe treatment modality for LMCC management.

Effect of tauroursodeoxycholic acid on PUFA levels and inflammation in an animal and cell model of hepatic endoplasmic reticulum stress.

The aim of this study was to evaluate hepatic polyunsaturated fatty acids (PUFAs) and inflammatory response in an animal and cell model of endoplasmic reticulum (ER) stress. Rats were divided into control, tunicamycin (TM)-treated, and TM + tauroursodeoxycholic acid (TUDCA)-treated groups. Hepatic ER stress was induced by TM and the ER stress inhibitor TUDCA was injected 30 min before induction of ER stress. Liver THLE-3 cells were treated with TM and TUDCA was administered in advance to decrease cytotoxic effects. Necroinflammation was evaluated in liver sections, while cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay kit. ER stress was confirmed by immunofluorescence and Western blot analysis of C/EBP-homologous protein and 78-kDa glucose-regulated protein. Arachidonic acid (C20:4n-6), dihomo-γ-linolenic acid (C20:3n-6), eicosapentaenoic acid (C20:5n-3), and docosahexaenoic acid (C22:6n-3) in liver tissue and THLE-3 cells were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). Phospholipase A2 (PLA2), cyclooxygenase (COX), and prostaglandin E2 (PGE2) were measured in tissue and cell samples. Hepatic ER stress was accomplished by TM and was alleviated by TUDCA. TM treatment significantly decreased PUFAs in both liver and THLE-3 cells compared to controls. PLA2, COX, and PGE2 levels were significantly increased in TM-treated rats and THLE-3 cells compared to controls. TUDCA leads to a partial restoration of liver PUFA levels and decreased PLA2, COX, and PGE2. This study reports decreased PUFA levels in ER stress and supports the use of omega-3 fatty acids in liver diseases demonstrating ER stress.

Impact of free thyroxine levels and other clinical factors on bare metal stent restenosis

ABSTRACT Objective Thyroid hormones have both direct and indirect effects on thermogenesis such as modulating vascular smooth muscle cell proliferation. However, the influence of more subtle changes in thyroid hormones on coronary atherosclerosis remains a matter of speculation. Smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relationship between free thyroxine (fT4) and ISR has not been studied. In the present study, we aimed to assess the role of preprocedural serum fT4 level on the development of ISR in patients undergoing coronary bare metal stent (BMS) implantation. Materials and methods We enrolled and analyzed clinical, biochemical, and angiographic data from 705 consecutive patients without a history of primary thyroid disease [mean age 60.3 ± 9.3 years, 505 (72%) male]; all patients had undergone BMS implantation and further control coronary angiography owing to stable or unstable angina pectoris. Patients were divided into 3 tertiles based on preprocedural serum fT4 levels. Results ISR was observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001). Using multiple logistic regression analysis, five characteristics emerged as independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent length, and preprocedural serum fT4 level. In receiver operating characteristics curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity (AUC: 0.75, p < 0.001) in predicting ISR. Conclusion Higher preprocedural serum fT4 is a powerful and independent predictor of BMS restenosis in patients with stable and unstable angina pectoris.

Syncope as the primary manifestation of hydatid cyst. Report of two cases with different etiologies.

Hydatid disease is a parasitic infestation that is caused by the larvae of the tapeworm Echinococcus granulosus. Clinical manifestations are extremely variable and related to the location and the size of the cysts. Syncope as the first clinical presentation of hydatid cyst is a very rare condition. Herein, we report two cases of patients with cardiac and pleural hydatid cysts who had syncope as the initial symptom.

Association of epicardial fat thickness with TIMI risk score in NSTEMI/USAP patients.

BACKGROUND: The association of epicardial adipose tissue (EAT) with coronary artery disease has been shown in previous studies. Furthermore, the relationship between EAT and acute coronary syndrome was studied recently. Herein, we investigated the relationship between EAT thickness and the thrombolysis in myocardial infarction (TIMI) risk score for non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (USAP). PATIENTS AND METHODS: The study included 144 patients with NSTEMI/USAP. The study population was divided into two subgroups according to TIMI risk scores as group I (≤ 4, n = 86) and group II (> 4, n = 58). Stepwise multivariable logistic regression analysis was used to assess the independent association of clinical parameters with TIMI risk score. RESULTS: EAT thickness was higher in group II than in group I (8.2 ± 2.1 vs. 6.2 ± 2.2, p < 0.001). Moreover, patients in group II had higher rates of multivessel disease and Gensini score (p < 0.001). In univariate linear regression analysis, EAT was positively correlated with TIMI risk score and Gensini score. Multivariate regression analysis showed that EAT thickness (OR: 1.56, 95 % CI: 1.17-2.08, p = 0.003), LVEF (OR: 0.93, 95 % CI: 0.85-0.98, p = 0.03), and Gensini score (OR: 1.36, 95 % CI: 1.24-1.98, p = 0.002) were independently associated with a higher TIMI risk score. CONCLUSION: In conclusion, EAT thickness is independently associated with TIMI risk score and may be an emerging risk factor for adverse events in NSTEMI/USAP patients.

Multiple thromboses at multiple sites. A known hereditary disease emerging late but suddenly and extensively.

Hyperhomocysteinemia is a significant independent, usually heritable, prothrombotic risk factor for atherothrombotic cardiovascular, cerebrovascular, and peripheral vascular disease. We report a 42-year-old woman who had multiple embolic events.

Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis.

Craniosynostosis, the fusion of one or more of the sutures of the skull vault before the brain completes its growth, is a common (1 in 2,500 births) craniofacial abnormality, approximately 20% of which occurrences are caused by gain-of-function mutations in FGF receptors (FGFRs). We describe a genetic and pharmacological approach for the treatment of a murine model system of Crouzon-like craniosynostosis induced by a dominant mutation in Fgfr2c. Using genetically modified mice, we demonstrate that premature fusion of sutures mediated by Crouzon-like activated Fgfr2c mutant is prevented by attenuation of signaling pathways by selective uncoupling between the docking protein Frs2alpha and activated Fgfr2c, resulting in normal skull development. We also demonstrate that attenuation of Fgfr signaling in a calvaria organ culture with an Fgfr inhibitor prevents premature fusion of sutures without adversely affecting calvaria development. These experiments show that attenuation of FGFR signaling by pharmacological intervention could be applied for the treatment of craniosynostosis or other severe bone disorders caused by mutations in FGFRs that currently have no treatment.

Course of serum lipoprotein(a) and acute phase protein levels in patients undergoing open heart surgery.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an important risk factor in the pathogenesis of coronary artery disease because of its thrombogenic and atherogenic properties. Lp(a) also displays another property by acting as an acute phase reactant. METHODS: In this work, the study group consisted of 20 male patients having coronary artery bypass under cardiopulmonary bypass (CPB). Preoperative and postoperative levels of plasma total cholesterol, triglyceride, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), alpha-1 antitrypsin (a1-AT), alpha-2 macroglobulin (alpha 2-MG), alpha-1 acid glycoprotein (alpha 1-AG), Lp(a) were measured in all patients one day before and after the 1st, 2nd, 4th, and 10th days of CPB. RESULTS: It was observed that the levels of Lp(a) levels gradually reached the preoperative levels at the 10th postoperative day period. Observed change of the Lp(a) levels was similar to that of the other acute phase proteins which are synthesized and released from liver. In contrast, alpha 2-MG has shown different behaviour in terms of operative values. The changes observed for all these 3 parameters were found to be statistically significant (p<0.01). CONCLUSIONS: The data has indicated that Lp(a) levels show similar progress with alpha 2-MG levels. It can be concluded that serum levels of Lp(a) after coronary arterial bypass decrease depending upon several factors and reach basal levels at the end of a 10 day-period of postoperation. The main cause for this decrease might result from the contact of blood with foreign surfaces of the heart-lung machine.

Risk factors and infant outcomes associated with umbilical cord prolapse.

OBJECTIVES: Our goal was to identify risk factors associated with umbilical cord prolapse and to review the perinatal outcome of cases of cord prolapse. METHODS: During the study years 77 cases were identified retrospectively. Associations between cord prolapse and potential risk factors were evaluated by means of the odds ratio. RESULTS: Of the 77 fetuses with umbilical cord prolapse 9.1% had a fetal weight of < 2500 gas compared with 9.4% for fetuses in control group (P > 0.05). The umbilical cord prolapse occurred in association with vertex presentation 66 times (85.7%), breech presentation nine times (11.7%) and transverse presentation two times (2.6%). The occurrence of breech presentation among the control cases was 2.6%, and that of transverse lie was 1.7% (P < 0.01). Case mothers were 1.6 times more likely to be multiparas compared with the control group (P < 0.01). The perinatal mortality rate was 39/1000. CONCLUSIONS: Our study showed that abnormal fetal presentation and multiparity are associated with an increased risk of umbilical cord prolapse. The association of risk of cord prolapse with low birth weight was statistically insignificant (P > 0.05). We suggest that the cesarean delivery decreased the risk of perinatal mortality among cases of cord prolapse.

Congestive heart failure associated with chronic venous insufficiency and leg ulcers secondary to an arteriovenous fistula caused by a shotgun wound 15 years ago.

We present a 65-year-old man who had a significant arteriovenous fistula between the right arteria profunda femoralis and vena profunda femoralis. He had evidence of chronic venous insufficiency and chronic leg ulcers on his right leg, and he had clinical findings of congestive heart failure. An arteriovenous fistula was responsible for all of clinical situation that had been caused by a shotgun wound 15 years ago. Using ultrasonography, after palpating a marked thrill and mass during physical examination, established the diagnosis of arteriovenous fistula. Angiography was performed both to delineate the suspected vascular anatomy and to show the coronary arteries. The patient was operated on and no complication was experienced during or after the procedure. Dramatic improvement was seen in the clinical picture just after surgery, and heart size markedly reduced both on chest X-ray and echocardiographic examination.

Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels and excretion of prostaglandins in stable renal allograft recipients.

AIMS: Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8-week withdrawal phase in pretreated patients. PATIENTS AND METHODS: Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-beta1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other anti-hypertensive drugs. RESULTS: Creatinine clearance as well as TGF-beta1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2. CONCLUSIONS: We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.

[Glomerulonephritis secondary to chronic infection of a ventriculoatrial shunt]. / Sekundäre Glomerulonephritis bei chronischer Infektion eines ventrikuloatrialen Shunts.

HISTORY AND ADMISSION FINDINGS: A 39-year-old man was referred for assessment of a nephrotic syndrome. He reported deteriorating health with bouts of fever and microhaematuria and proteinuria in the past year. At the age of 24 years a ventriculoatrial shunt had been inserted for an internal hydrocephalus. At another hospital he was given steroids for a nephrotic syndrome suspected of being associated with membranoproliferative glomerulitis, but the disease progressed. On admission he had severe generalised oedema with a temperature of 38,5;C. His general condition was poor. He had no neck stiffness. INVESTIGATIONS: Parameters of inflammation were raised. Serum creatinine and creatinine clearance were normal. Levels of complements C3 and C4 were reduced. The proteinuria was 9g/24h. Renal biopsy revealed type 1 membranoproliferative glomerulonephritis. Micrococcus roseus/varians was demonstrated several times by aerobic blood cultures. TREATMENT AND COURSE: The findings suggested chronically infected ventriculoatrial shunt as cause of the glomerulonephritis. The shunt was, therefore, removed. The same pathogens were grown from it on aerobic culture medium. Six months after removal and replacement of the shunt and treatment of the infection the proteinuria had fallen to 0.45 mg/h; serum creatinine was 1.0 mg/dl. CONCLUSION: When membranoproliferative glomerulonephritis has been demonstrated, secondary forms should be considered in the differential diagnosis. In most cases specific treatment can prevent progression of the renal disease.

Correlation of perineural invasion on radical prostatectomy specimens with other pathologic prognostic factors and PSA failure.

OBJECTIVE: The aim of this study is to evaluate the relationship between perineural invasion (PNI) and other pathologic prognostic factors in radical retropubic prostatectomy (RRP) specimens and also to assess the role of PNI in prostate-specific antigen (PSA) recurrence after RRP. METHOD: 191 consecutive patients had undergone RRP for clinically localized prostate cancer between 1992 and 2000. PNI in RRP specimens and its relation to histopathologic stage and surgical margins is investigated retrospectively. PNI, histopathologic stage, surgical margin status, Gleason score and PSA parameters were used as variables in multivariate analysis for recurrence. RESULTS: PNI is correlated statistically significantly with histopathologic stage, positive surgical margins, specimen Gleason score and recurrence. Mean time to failure was earlier in patients with PNI than patients without PNI (56 vs. 73 months, log-rank 15.67, p<0.001). Lymph node involvement, positive surgical margins and PNI remained as independent predictors of recurrence in multivariate analysis. All patients with PNI, positive surgical margins and lymph node metastasis failed in 6 months. CONCLUSION: PNI is an important prognostic factor that should be taken into consideration in clinical patient management and follow-up after RRP. The presence of PNI together with positive surgical margins and lymph node metastasis may warrant early adjuvant treatment.

Role of DNA methylation at GATC sites in the dnaA promoter, dnaAp2.

DnaA protein is required for the initiation of DNA replication at the bacterial chromosomal origin, oriC, and at the origins of many plasmids. The concentration of DnaA protein is an important factor in determining when initiation occurs during the cell cycle. Methylation of GATC sites in the dnaAp2 promoter, two of which are in the -35 and -10 sequences, has been predicted to play an important role in regulating dnaA gene expression during the cell cycle because the promoter is sequestered from methylation immediately following replication. Mutations that eliminate these two GATC sites but do not substantially change the activity of the promoter were introduced into a reporter gene fusion and into the chromosome. The chromosomal mutants are able to initiate DNA replication synchronously at both moderately slow and fast growth rates, demonstrating that GATC methylation at these two sites is not directly involved in providing the necessary amount of DnaA for precise timing of initiation during the cell cycle. Either sequestration does not involve these GATC sites, or cell cycle control of DnaA expression is not required to supply the concentration necessary for correct timing of initiation.