Beta-Blockers as an Immunologic and Autonomic Manipulator in Critically Ill Patients: A Review of the Recent Literature.

The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients.

High spontaneous clearance of symptomatic iatrogenic acute hepatitis C genotype 4 infection.

Acute hepatitis C (AHC) infection resolves spontaneously in 15% to 40% of patients. Factors favoring spontaneous viral clearance remain undefined. In this study, predictors of spontaneous viral clearance in patients with symptomatic AHC were investigated. Epidemiological, clinical, and virologic parameters were also examined. Patients with symptomatic AHC were enrolled and followed up prospectively. The patients were followed up every 2 weeks in the first month and then monthly for the following 5 months, with a follow-up visit 6 months after the last hepatitis C virus (HCV)-RNA negative sample for those who had cleared the virus. Interleukin (IL)-28B.rs12979860 single-nucleotide polymorphism and HCV genotype were tested at baseline. HCV-RNA was tested during each visit. Patients who remained RNA-positive at 24 weeks were treated with pegylated interferon plus ribavirin for 24 weeks. A total of 30 patients, mostly with iatrogenically acquired AHC genotype 4 infections completed 6-months' follow-up, to either spontaneous clearance or start of treatment. The mean age of the patients was 37 ± 13 years. In total, 67% of patients were females, and the mean incubation period was 7.6 ± 3.5 weeks. Viral clearance occurred spontaneously in 19 (63.3%) patients. The average time to clearance was 24.3 ± 9.6 weeks. A total of 11 patients received therapy, and 8 (72.7%) cleared the virus and had a sustained virologic response to the treatment 24 weeks after the therapy. A total of three patients were treatment nonresponders. IL28B.rs12979860 CC genotype, female gender, and viremia level were not associated with self-limiting AHC in this cohort. In conclusion, patients with symptomatic AHC genotype 4 infection caused by an iatrogenic exposure had higher rates of spontaneous resolution than previously reported. Predicting spontaneous viral clearance after iatrogenic AHC exposure was not possible in this population.

Finding Wolbachia in Filarial larvae and Culicidae Mosquitoes in Upper Egypt Governorate.

Wolbachia is an obligatory intracellular endosymbiotic bacterium, present in over 20% of all insects altering insect reproductive capabilities and in a wide range of filarial worms which is essential for worm survival and reproduction. In Egypt, no available data were found about Wolbachia searching for it in either mosquitoes or filarial worms. Thus, we aimed to identify the possible concurrent presence of Wolbachia within different mosquitoes and filarial parasites, in Assiut Governorate, Egypt using multiplex PCR. Initially, 6 pools were detected positive for Wolbachia by single PCR. The simultaneous detection of Wolbachia and filarial parasites (Wuchereria bancrofti, Dirofilaria immitis, and Dirofilaria repens) by multiplex PCR was spotted in 5 out of 6 pools, with an overall estimated rate of infection (ERI) of 0.24%. Unexpectedly, the highest ERI (0.53%) was for Anopheles pharoensis with related Wolbachia and W. bancrofti, followed by Aedes (0.42%) and Culex (0.26%). We also observed that Wolbachia altered Culex spp. as a primary vector for W. bancrofti to be replaced by Anopheles sp. Wolbachia within filaria-infected mosquitoes in our locality gives a hope to use bacteria as a new control trend simultaneously targeting the vector and filarial parasites.

Xenomonitoring of different filarial nematodes using single and multiplex PCR in mosquitoes from Assiut Governorate, Egypt.

Wuchereria bancrofti, Dirofilaria immitis, and Dirofilaria repens are filarial nematodes transmitted by mosquitoes belonging to Culex, Aedes, and Anopheles genera. Screening by vector dissection is a tiresome technique. We aimed to screen filarial parasites in their vectors by single and multiplex PCR and evaluate the usefulness of multiplex PCR as a rapid xenomonitoring and simultaneous differentiation tool, in area where 3 filarial parasites are coexisting. Female mosquitoes were collected from 7 localities in Assiut Governorate, were microscopically identified and divided into pools according to their species and collection site. Detection of W. bancrofti, D. immitis, and D. repens using single PCR was reached followed by multiplex PCR. Usefulness of multiplex PCR was evaluated by testing mosquito pools to know which genera and species are used by filarial parasites as a vector. An overall estimated rate of infection (ERI) in mosquitoes was 0.6%; the highest was Culex spp. (0.47%). W. bancrofti, D. immitis, and D. repens could be simultaneously and differentially detected in infected vectors by using multiplex PCR. Out of 100 mosquito pools, 8 were positive for W. bancrofti (ERI of 0.33%) and 3 pools each were positive for D. immitis and D. repens (ERI 0.12%). The technique showed 100% sensitivity and 98% specificity. El-Nikhila, El-Matiaa villages, and Sahel Seleem district in Assiut Governorate, Egypt are still endemic foci for filarial parasites. Multiplex PCR offers a reliable procedure for molecular xenomonitoring of filariasis within their respective vectors in endemic areas. Therefore, it is recommended for evaluation of mosquito infection after lymphatic filariasis eradication programs.

Non-Surgical Bleeding and Transurethral Resection of the Prostate (TURP) Syndrome after TURP Surgery: A Case Report and Literature Review.

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients' coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA.

Differential Effects of Ventricular Pacing Sites of Contraction Synchrony and Global Cardiac Performance.

BACKGROUND: Quantification of left ventricular (LV) dyssynchrony allows for objective measures of resynchronization therapy (CRT) effectiveness. We tested the hypothesis that site of LV pacing, fusion beats and baseline contractility alter contraction synchrony as quantified by regional and global measures of LV performance. METHODS AND RESULTS: In 8 open-chested pentobarbital-anesthetized canine preparations we compared the effects of right atrial (RA), RA-high right ventricular (RV) free wall, as a model of left bundle branch block contraction pattern, RA-LV apex (LVa), RA-LV free wall (LVfw), and RA-RV-apical LV (CRTa) and RA-RV-free wall LV (CRTfw), as CRT. LV pressure-volume loops recorded using high-fidelity pressure and conductance catheters and echocardiographic angle-corrected color-coded strain imaging of mid-LV short axis views analyzed radial strain from six segments. To control for contractile state esmolol-induced beta blockage was studied, and in 5 dogs to control for RA and ventricular pacing fusion beat artifacts, repeat studies were done following AV node ablation. RA-RV pacing reduced stroke work (SW) (57±18 to 33±13* mmHg·mL,*p<0.05 vs RA pacing), decreased LV end-diastolic volume and induced marked radial dyssynchrony (maximal time difference between peak segmental strain) from 31±15 to 234±60* ms. Changes in radial dyssynchrony correlated significantly with changes in SW (r=-0.53, p<0.01). Dyssynchrony improved with both CRTa and CRTfw (69*±31 and 98*±63 ms, respectively) while SW only improved with CRTa (62±22* and 37±13 mmHg·mL, respectively * p<0.05 vs RV pacing). CRTa also tended to increased LV end-diastolic volume over RA-RV. Esmolol slowed HR from 118±10 to 108±10 beats/min* and tended to decrease contractility (end-systolic elastance (Ees) from 12.1±7.9 to 8.9±3.9 mmHg/ml, p=0.167) but did not alter the degree of RV-pacing induced dyssynchrony. AV ablation had no effect on the observed apical and free wall contraction differences seen during baseline conditions. CONCLUSION: Although both CRTa and CRTfw reduced contraction dyssynchrony, CRTa tended to improve global LV performance more by increasing end-diastolic volume. Thus, CRT may improve global LV performance differently, depending on the LV pacing site.

Estimating left ventricular contractility using inspiratory-hold maneuvers.

OBJECTIVE: To compare estimates of left ventricular (LV) end-systolic elastance created by inferior vena caval (IVC) occlusion with those by apneic continuous positive airway pressure (CPAP). DESIGN AND SETTING: Prospective interventional study in a university large animal research laboratory. SUBJECTS: Sixteen intact, pentobarbital-anesthetized mongrel male dogs. INTERVENTIONS: Insertion of LV conductance and pressure catheters, then during apnea sequentially performed IVC occlusion and CPAP of 5, 10, and 15 mmHg for 10 s, each interspersed by positive-pressure breathing. In the final 11 dogs runs were repeated during both esmolol (2 mg min-1) and dobutamine (5 microg kg-1 min-1) infusions. MEASUREMENTS: LV pressure-volume relationships during apneic baseline and then as LV end-diastolic volume decreased by each maneuver to calculate LV end-systolic elastance and preload-recruitable stroke work as measures of contractility. RESULTS: End-systolic elastance estimated at 5 mmHg CPAP levels and IVC occlusions were similar while 10 and 15 mmHg CPAP gave different values. However, end-systolic elastance was lower during esmolol infusion and higher during dobutamine for all CPAP and IVC occlusion maneuvers. Preload-recruitable stroke work measures were similar across maneuvers. With increasing CPAP the LV filling and end-systolic elastance were progressively shifted upward and to the left, with volume on the x-axis, consistent with an unaccounted for increase in intrathoracic pressure. CONCLUSIONS: The use of 5 mmHg CPAP-induced preload-reduction allows estimation of LV end-systolic elastance and preload-recruitable stroke work in intact dogs. Increasing CPAP to more than 10 mmHg creates estimates of LV contractility that are different but covary with IVC occlusion-derived values.