Predictive factors of recurrence after pediatric acute pericarditis

ObjectiveThe predisposing factors for pericarditis recurrence in the pediatric population have not yet been established. This study aimed to define the risk factors for the unfavorable prognosis of pediatric acute pericarditis.MethodsThis was a retrospective study that included all patients with acute pericarditis treated from 2011 to 2019 at a tertiary referent pediatric center.ResultsThe study included 72 children. Recurrence was observed in 22.2% patients. Independent risk factors for recurrence were: erythrocyte sedimentation rate ≥ 50 mm/h (p = 0.003, OR 186.3), absence of myocarditis (p = 0.05, OR 15.2), C-reactive protein ≥ 125 mg/L (p = 0.04, OR 1.5), and non-idiopathic etiology pericarditis (p = 0.003, OR 1.3). Corticosteroid treatment in acute pericarditis was associated with a higher recurrence rate than treatment with non-steroid anti-inflammatory therapy (p = 0.04). Furthermore, patients treated with colchicine in the primary recurrence had lower recurrence rate and median number of repeated infections than those treated without colchicine (p = 0.04; p = 0.007, respectively).ConclusionIndependent risk factors for recurrence are absence of myocarditis, non-idiopathic etiology pericarditis, C-reactive protein ≥ 125 mg/L, and erythrocyte sedimentation rate ≥ 50 mm/h. Acute pericarditis should be treated with non-steroid anti-inflammatory therapy. A combination of colchicine and non-steroid anti-inflammatory drugs could be recommended as the treatment of choice in recurrent pericarditis.     

Bacteriophage Cocktails in the Post-COVID Rehabilitation

Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota. In the present study, two complex phage cocktails targeting multiple bacterial species were used in the rehabilitation of thirty patients after COVID-19, and the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae was evaluated for the first time using real-time visualization on a 3D Cell Explorer microscope. Application of phage cocktails for two weeks showed safety and the absence of adverse effects. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, together with an erythrocyte sedimentation rate (ESR), was detected. This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.     

Prospective comparison of valacyclovir and oral ganciclovir for prevention of cytomegalovirus disease in high-risk renal transplant recipients

AIMS: To compare the efficacy, costs and safety of oral ganciclovir and valacyclovir in the prophylaxis of cytomegalovirus (CMV) disease in renal transplant (RTx) recipients at high risk of CMV disease. METHODS: A total of 83 patients were prospectively randomized to 3-month treatment with either oral ganciclovir (3 g/day) or oral valacyclovir (8 g/day). A 3rd group received no prophylaxis. Forty-nine patients were considered to be at high risk of CMV disease due to D+R- serologic status, OKT3/ATG treatment and/or acute rejection within 12 months after RTx. Twenty-three high-risk patients were treated with ganciclovir (GAN group), 17 patients with valacyclovir (VAL group), and 9 patients received no prophylaxis (C group). RESULTS: No significant differences were found among the groups in their demographic characteristics, immunosuppressive protocols, D/R CMV serology, or CMV risk factors. The 12-month incidence of CMV disease was 89% in the C group compared with 9% in the GAN group and 6% in the VAL group (p < 0.001, GAN or VAL vs. C; p = 0.713, GAN vs. VAL). Treatment failure (death, graft loss, CMV disease or withdrawal from study) occurred in 17, 6, and 89% in the GAN, VAL, and C groups, respectively (p < 0.001, GAN or VAL vs. C; p = 0.285, GAN vs. VAL). The average CMV-associated costs per patient were EUR 3,161, 3,757, and 7,247 in the GAN, VAL, and C groups, respectively (p = 0.027). CONCLUSION: Valacyclovir and oral ganciclovir are equally effective in the prophylaxis of CMV disease in high-risk RTx patients. Both regimens are cost-effective and help reduce CMV-associated costs by nearly 50% compared with patients without prophylaxis.     

Elevated blood lead resulting from maxillofacial gunshot injuries with lead ingestion.

PURPOSE: The purpose of this study was to identify the contribution of ingested lead particles to elevated blood lead concentrations in victims of gunshot injury to the maxillofacial region. PATIENTS AND METHODS: As part of a larger study of the effects of retained lead bullets on blood lead, a retrospective review of study findings was completed on 5 of 8 patients who sustained injuries to the maxillofacial region. These 5 patients were recruited into the larger study within 11 days of injury and showed a penetration path for the projectile that engaged the upper aerodigestive tract. All subjects were recruited from patients presenting for care of their gunshot injuries to a large inner-city trauma center with a retained bullet resulting from a gunshot injury. An initial blood lead level was measured for all recruited patients and repeated 1 to 17 weeks later. Medical history was taken along with a screening and risk factor questionnaire to determine other potential or actual sources (occupational/recreational) of lead exposure. (109)Cd K-shell x-ray fluorescence determinations of bone lead were completed to determine past lead exposure not revealed by medical history and risk factor questionnaire. Radiographs taken of the abdomen and chest, required as a part of the patient's hospital care, were retrospectively reviewed for signs of metallic fragments along the aerodigestive tract. RESULTS: All 5 patients retained multiple lead pellets or fragments at the site of injury, sustained fractures of the facial bones, and showed increases in blood lead. Three of the 5 study subjects who sustained maxillofacial gunshot injuries involving the mouth, nose, or throat region showed metallic densities along the gastrointestinal tract indicative of ingested bullet fragments. Each patient with ingested bullet fragments showed rapid elevation of blood lead exceeding 25 microg/dL and sustained increases well beyond the time when all ingested fragments were eliminated. A 3-year follow-up on these 3 patients showed significantly sustained elevation of blood lead but less than that observed during the initial 6 months after injury. None of the 5 study subjects showed any evidence of metallic foreign bodies within the tracheobronchial regions indicative of aspiration. CONCLUSION: Ingestion of lead fragments can result from gunshot injuries to the maxillofacial region and may substantially contribute to a rapid increase in blood lead level. Prompt diagnosis and elimination of ingested lead fragments are essential steps necessary to prevent lead being absorbed from the gastrointestinal tract. Increased blood lead in victims after gunshot injuries must be fully evaluated for all potential sources, including recent environmental exposure, absorption of lead from any remaining bullets in body tissues, and the possibility of mobilization of lead from long-term body stores such as bone.     

The effect of imidazole on the isometric contractility of the isolated hemidiaphragm of the rat.

Imidazole (0.73-15.9mM) was found to increase both tension developed Td and the maximum rats of rise of tension, dT/dtmax, in the isolated hemidiaphragm of the rat during indirect stimulation. Similar effects were obtained during direct stimulation and in the presence of d-tubocurarine. Imidazole (0.73-22 mM) antagonized the action of d-tubocurarine. This effect was particularly pronounced in preparations pretreated with imidazole. Propranolol did not significantly change the action of imidazole on Td and dT/dtmax during direct stimulation. Similarly, propranolol did not affect the action of low concentrations of imidazole during indirect stimulation. When present in the bath for periods of time longer than 15 min, propranolol significantly depressed the effect of even high concentrations of imidazole on Td and dT/dtmax during indirect stimulation. Histamine (0.18-0.91 mM) did not affect either Td or dT/dtmax. In the experiments in vivo, imidazole (12.5-100 mg/kg) produced a small increase both in Td and dT/dtmax of the gastrocnemius muscle during sciatic nerve stimulation. The available evidence indicates that the action of imidazole on Td and dT/dtmax is not connected with its action on phosphodiesterase, but it is most probably due to a direct action on the muscle.     

Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion

Intravascular cancer cell adhesion plays a significant role in the metastatic process. Studies indicate that galectin-3, a member of the galectin family of soluble animal lectins, is involved in carbohydrate-mediated metastatic cell heterotypic (between carcinoma cells and endothelium) and homotypic (between carcinoma cells) adhesion via interactions with the tumor-specific Thomsen-Friedenreich glycoantigen (TFAg). We hypothesized that blocking the galectin-3 carbohydrate recognition domain with synthetic peptides would significantly reduce metastasis-associated carcinoma cell adhesion. To test this hypothesis, we identified peptide antagonists of the galectin-3 carbohydrate recognition domain using combinatorial bacteriophage display technology. The peptides bound with high affinity to purified recombinant galectin-3 protein (K(d) approximately 17-80 nM) and to cell surface galectin-3. Experiments with a series of recombinant serially truncated galectin-3 mutants indicated that the peptides bound the carbohydrate recognition domain of galectin-3. Furthermore, the peptides did not bind the carbohydrate recognition domain of other galectins and plant lectins. Synthetic galectin-3 carbohydrate recognition domain-specific peptides blocked the interaction between galectin-3 and TFAg and significantly inhibited rolling and stable heterotypic adhesion of human MDA-MB-435 breast carcinoma cells to endothelial cells under flow conditions, as well as homotypic tumor cell aggregation. These results demonstrate that carbohydrate-mediated, metastasis-associated tumor cell adhesion could be inhibited efficiently with short synthetic peptides which do not mimic naturally occurring glycoepitopes yet bind to the galectin-3 carbohydrate recognition domain with high affinity and specificity.     

Artificial iris-lens diaphragm in reconstructive surgery for aniridia and aphakia

PURPOSE: To determine the efficacy and safety of surgical implantation of artificial iris-lens diaphragm in patients with anatomic or functional iris deficiencies, aphakia or cataract. SETTING: Svyatoslav Fyodorov MNTK Eye Microsurgery, Cheboksary, Russia. METHODS: Twenty eyes of 19 consecutive patients with combined iris and lens pathology of traumatic or congenital etiology were identified for an interventional noncomparative case series. The newly proposed model of an elastic iris-lens diaphragm with a colored haptic and additional support elements was implanted using various fixation approaches. RESULTS: Fifteen eyes (75%) experienced improvement in corrected visual acuities. The best spectacle-corrected visual acuity (BSCVA) in 2 eyes did not change, while the uncorrected visual acuity (UCVA) in these eyes increased. There were 3 eyes in which BSCVA deteriorated with no change or even slight improvement in UCVA. All patients were satisfied with the cosmetic results of the surgery and reported a decrease in glare and photophobia. There was 1 intraoperative complication of vitreous hemorrhage. Postoperatively, 2 cases of hyphema, 1 case of ciliochoroidal detachment, 4 eyes with exaggerated immediate postoperative reaction, and 1 eye with persistent low-grade cyclitis were observed. In 1 eye, there was persistent intraocular pressure rise. One eye showed signs of cystoid macular edema. No iris-lens diaphragm decentrations and no new or extensions of old retinal detachments were seen during the follow-up period. CONCLUSIONS: Artificial iris-lens diaphragm implantation effectively improved postoperative outcomes by correcting aphakia, reducing glare disability, and addressing cosmetic issues faced by iris-deficient, and aphakic or cataract patients. Although the iris-lens diaphragm appears to be safe, long-term results must be clarified in studies with longer follow-up and a larger patient population.     

Impact of UVR-A on whole human lenses, supernatants of buffered human lens homogenates, and purified argpyrimidine and 3-OH-kynurenine

PURPOSE: Yellow chromophores and fluorescent compounds accumulate in the lens with age. Some of these compounds are photochemically active. The present study aimed to examine the photochemical effect of ultraviolet radiation-A (UVR-A) on the human lens. METHODS: Intact human lenses and supernatants of buffered lens homogenates were exposed to UVR-A. The effect of UVR-A was evaluated by time-resolved and steady-state fluorescence spectroscopy, visual evaluation of colour and protein gel electrophoresis. RESULTS: Intact lenses exposed to UVR-A showed no changes in time-resolved or steady-state fluorescence properties but the yellow coloration was visibly attenuated. The supernatants of buffered lens homogenates exposed to UVR-A demonstrated a reduction in time-resolved and steady-state fluorescent properties and protein cross-linking. CONCLUSIONS: Exposure of the intact lens to UVR-A causes chromophore bleaching without affecting fluorescence, indicating that non-fluorescent chromophores have been destroyed. After homogenization, both chromophores and fluorophores from the lens suffer damage and proteins aggregate. This indicates that powerful mechanisms of protection against UVR-A found in the intact lens are disturbed by homogenization of the lens, suggesting that isolated lens proteins cannot be used as a model system for studying cataractogenesis. Hypothetically, the protective mechanism could be related to the rigidly packed three-dimensional structure of the lens proteins or to the abundance of antioxidative and free radical scavenging defence systems.