Frequency of Background and Radiation-Induced Apoptosis in Leukocytes of Individuals with α-Thalassemia Variants,Assessed by the Neutral Comet Assay

To study effects of ionizing radiation on apoptosis induction in leukocytes of α-thalassemia (α‐thal) variants compared to normal controls, venous blood samples were obtained from 10 healthy volunteers and 30 α-thal patients. Different types α-thal were diagnosed by multiplex polymerase chain reaction (PCR). Blood samples were irradiated with three Gy gamma rays, used for comet assay, immediately or 48 h after irradiation. Results show that the frequency of background as well as apoptosis in silent α-thal carriers, α-thal carriers and controls was similar but there was a significant difference between Hb H patients and other groups in the study. The increased apoptosis in Hb H patients might suggest that accumulation of β-globin and oxidative stresses are effective in causing apoptosis, and cells from these patients are more vulnerable to damage from radiation-induced toxic substances. Therefore, from α-thal patients, those with Hb H disease might be considered as radiosensitive in terms of apoptosis formation.     

Multicenter Evaluation of the Clinical Outcomes of Daptomycin with and without Concomitant β-Lactams in Patients with Staphylococcus aureus Bacteremia and Mild to Moderate Renal Impairment

Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and Staphylococcus aureus bacteremia treatment failure. In light of recent data demonstrating the successful use of β-lactam plus daptomycin in very difficult cases of S. aureus bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant β-lactams. We identified 106 patients who received daptomycin for S. aureus bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a β-lactam (87% versus 78%; P = 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%; P = 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with β-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.     

Reducing Morbidity of Pelvic and Retroperitoneal Lymphadenectomy

Lymphadenectomy is utilized in both pelvic and retroperitoneal oncological surgery as a means to eradicate locoregional disease, improve staging accuracy and guide adjuvant therapy. However, pelvic and retroperitoneal lymphadenectomy have the potential for morbidity including lymphatic injury, vascular injury, thromboembolic events and neurologic injury. Across the spectrum of urologic malignancies, the evidence supporting both the necessity and the extent of lymphadenectomy varies considerably. Awareness of the potential for injury and ways to avoid and manage the most common complications is necessary to decrease the morbidity associated with these procedures.     

Association between vision and cognitive function among community-dwelling older adults in Selangor, Malaysia

AIM: To determine the association between distance and near visual acuity (VA) and cognitive function among older adults in Selangor, Malaysia. METHODS: A total of 230 older adults (age ≥60y) participated in this study. Habitual distance and near VA were measured using the Early Treatment Diabetic Retinopathy Study Chart and Lighthouse Near Visual Acuity Chart, respectively. Global cognitive function was assessed using the Mini-Mental State Examination (M-MSE) and the Malay language version of the Montreal Cognitive Assessment (M-MoCA). Digit Symbol (DS) subtest was used to measure information processing. RESULTS: No significant association was observed between vision and M-MSE and M-MoCA scores. However, poor distance and near VA were found to be significantly associated with low DS scores [distance VA: β=-0.01, R2=0.1, P=0.02; odds ratio (OR)=2.84, 95% confidence interval (CI), 1.10-7.33, P=0.03; near VA: β=-0.05, R2=0.08, P=0.00; OR=3.32, 95%CI, 1.28-8.59, P=0.01]. CONCLUSION: Poor vision is associated with a decline in information processing in older adults and substantiates the importance of preserving good vision in maintaining cognitive function.     

Iron polymaltose versus ferrous gluconate in the prevention of iron deficiency anemia of infancy

We prospectively compared the efficacy and safety of iron deficiency anemia prophylaxis with iron gluconate (IG) or iron polymaltose complex (IPC) in healthy infants attending a community pediatric center. Participants were randomly assigned to receive one of the test drugs from age 4 to 6 months to age 12 months. Parents/guardians were given extensive information on iron-rich diets and anemia prevention. Main outcome measures were blood levels of hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width, and serum iron, ferritin, and transferrin, in addition to adverse effects. One hundred five children completed the study: 53 in the IG group and 52 in the IPC group Mean hemoglobin levels at study end were significantly higher in the IG group (12.04±0.09 g/dL vs. 11.68±0.11, P<0.014). A hemoglobin level <11 g/dL was detected in 3 infants of the IG group, and in 10 infants of the IPC group (P<0.04). Adverse effects (spitting, vomiting, diarrhea, constipation, discolored teeth) were significantly more common in the IG group (47% vs. 25%, P>0.025). In conclusion, both oral IG and IPC prevent iron deficiency anemia in infants. Iron gluconate seems to be more effective but less tolerable.     

Infantile spasms and encephalopathy without preceding neonatal seizures caused by KCNQ2 R198Q,a gain‐of‐function variant

Variants in KCNQ2 encoding for K_v7.2 neuronal K⁺ channel subunits lead to a spectrum of neonatal‐onset epilepsies, ranging from self‐limiting forms to severe epileptic encephalopathy. Most KCNQ2 pathogenic variants cause loss‐of‐function, whereas few increase channel activity (gain‐of‐function). We herein provide evidence for a new phenotypic and functional profile in KCNQ2‐related epilepsy: infantile spasms without prior neonatal seizures associated with a gain‐of‐function gene variant. With use of an international registry, we identified four unrelated patients with the same de novo heterozygous KCNQ2 c.593G>A, p.Arg198Gln (R198Q) variant. All were born at term and discharged home without seizures or concern of encephalopathy, but developed infantile spasms with hypsarrhythmia (or modified hypsarrhythmia) between the ages of 4 and 6 months. At last follow‐up (ages 3–11 years), all patients were seizure‐free and had severe developmental delay. In vitro experiments showed that Kv7.2 R198Q subunits shifted current activation gating to hyperpolarized potentials, indicative of gain‐of‐function; in neurons, K_v7.2 and K_v7.2 R198Q subunits similarly populated the axon initial segment, suggesting that gating changes rather than altered subcellular distribution contribute to disease molecular pathogenesis. We conclude that KCNQ2 R198Q is a model for a new subclass of KCNQ2 variants causing infantile spasms and encephalopathy, without preceding neonatal seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here     

Post-thoracotomy pain relief: Thoracic paravertebral block compared with systemic opioids

BackgroundWe evaluated the safety and efficacy of thoracic paravertebral block as a method of pain relief after thoracotomy in comparison with systemic opioids.Study designRandomized controlled trial.MethodsWe scheduled 40 patients divided into two groups to receive either 20 ml bupivacaine (0.5%) incremental injections for intra and postoperative analgesia via a catheter inserted in the thoracic paravertebral space. The other 20 patients received systemic morphine for postoperative analgesia. We recorded postoperative Visual Analog Scale pain score, total morphine consumption, time to first analgesic request, changes in pulmonary functions and side effects.ResultsVisual analogue scale (VAS) at rest was lower in the paravertebral group at all measurement points except at 16, 20 and 24 h postoperatively. Pain on coughing showed significant difference (P value < 0.05) at 8 and 16 h but not at 24 h. Post-operative consumption of morphine was 36 (22–42) mg in the control group versus 9 (2–22) mg in the paravertebral block group (PVB) (P value = 0.003). Total bupivacaine dose used in the PVB group in the first 24 h was 300–420 mg. For time to first analgesic request it was significantly longer in the morphine group than the paravertebral block group. VAS at first analgesic request was not statistically different between the two groups.There was no significant difference between the two groups as regards to peak expiratory flow rate (PEFR) preoperatively, after 12 h or 24 h.There was a significant reduction in the incidence of side effects in the TPVB group compared to morphine group concerning vomiting and pruritus.no local anesthetic toxicity was reported.ConclusionWe conclude that thoracic PVB provides effective post thoracotomy analgesia supported by lower VAS pain scores at rest and on coughing compared to intravenous morphine with significant less incidence of side effects.