Second cycle of intralesional Collagenase Clostridium histolyticum for Peyronie's disease using the modified shortened protocol: Results from a retrospective analysis

The purpose of this study was to evaluate the effectiveness and safety of the second cycle of Collagenase Clostridium histolyticum injections using the modified shortened protocol. We performed a retrospective analysis on patients who had already undergone the first cycle of injections using the modified shortened protocol and requested more injections to improve the remaining curvature. The International Index of Erectile Function, the Peyronie's Disease Questionnaire and the Global Assessment of Peyronie's Disease questionnaire were self-administered to all patients. All the parameters were recorded at baseline, after the first cycle and after the second cycle of injections. All adverse events were recorded. Seventeen patients completed two cycles of injections. All patients had a reduction of the initial curvature after the first cycle, with a mean improvement of 17.4° (27.4%). After the second cycle, the reduction of the curvature was 7.9° (17.1%), and 29.4% of patients had no further improvement. No severe side effect was recorded. The results of the present study confirm the effectiveness and safety of the modified shortened protocol of Collagenase C. histolyticum injections for Peyronie's disease. However, the second cycle of three injections may be less effective, and patients may not be completely satisfied.     

Heart transplant recipients with confirmed 2019 novel coronavirus infection: The Detroit experience

A chronic immunosuppressed state as in solid organ transplant recipients is a reported risk factor for the novel 2019 coronavirus infection. Patients with a history of orthotopic heart transplant (OHT) at a tertiary care transplant center in Detroit, Michigan were retrospectively reviewed from March until May 2020. Clinical parameters and outcomes of 5 OHT recipients and one combined heart–lung recipient with confirmed SARS-CoV-2 were obtained. The cohort was predominately African American males with median age of 59 years (interquartile range, 48.25-73.25). All patients were classified as having mild–moderate disease; none required intubation or ICU admission with no deaths. The most common presenting symptoms were fever and shortness of breath 83% (n = 5), followed by cough and chills 67% (n = 4). All admitted patients (n = 5) received hydroxychloroquine and 3 received high-dose steroids. Antimetabolites were held for 2 patients (33.3%). The calcineurin inhibitor trough goal was decreased in only 1 patient; 3 other patients, without change in goal, required calcineurin inhibitor dosage reduction. Two patients requiring readmission presented 7 and 23 days after initial symptoms onset. In conclusion, our experience with OHT patients infected by the SARS-CoV-2 virus did not have an elevated risk of severe infection. Impact of modifying immunosuppression remains unclear.     

Acute acquired concomitant esotropia associated with myopia: is the condition related to any binocular function failure?

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the sensory motor state, accommodation, and accommodative convergence to accommodation ratio (AC/A) in a cohort of...     

Infusion-Related Reaction Following Daptomycin Two-Minute Rapid Intravenous Administration

Background:

Erythroderma, or red man’s syndrome, is a common infusion-related reaction following vancomycin administration. Erythroderma following daptomycin rapid infusion has not been documented.

Objective:

To report a case of erythroderma following daptomycin 2-minute intravenous (IV) injection.

Case Report:

A review of published literature suggests that this is the first published case of a flushing (nonallergic) reaction resulting from a 2-minute IV injection of daptomycin that is not present with standard IV infusion. A 69-year-old woman following right knee reconstructive surgery presented with right knee joint swelling, purulent discharge, and fever. Subsequently, she was diagnosed with a presumed postsurgical infection and was initiated on vancomycin therapy. Following removal of the infected hardware, the patient was discharged and continued outpatient vancomycin therapy. The patient’s renal function began to decline and therapy was discontinued. Daptomycin 6 mg/kg every 48 hours was initiated via 2-minute IV push. On the initial dose, approximately 2 hours post IV infusion, the patient began to notice redness and a warm sensation on her face, neck, and upper part of the chest. Diphenhydramine 25 mg provided limited immediate relief, but all symptoms subsided within 3 to 4 hours. The patient received her next dose 48 hours later over a 40-minute IV infusion with no adverse effects. Subsequent infusions continued at the same dose over 30 minutes for 4 weeks with no further adverse effects.

Conclusion:

A 2-minute intravenous injection of daptomycin in this patient yielded a reaction that was not present on rechallenge with standard, extended infusion.Key Words: daptomycin, erythroderma, rapid infusion, red man’s syndrome, Staphylococcus aureusDaptomycin is a bactericidal lipopeptide antibiotic commonly used for drug-resistant gram-positive pathogens.¹ Daptomycin was originally approved by the US Food and Drug Administration (FDA) in September 2003 as a once-daily 30-minute intravenous (IV) infusion. In November 2010, the FDA approved a 2-minute rapid IV injection based on data from 2 consecutive pharmacokinetic and safety evaluation studies.^2,3 Daptomycin pharmacokinetic parameters were comparable with the 2-minute IV administration group when compared to the 30-minute IV infusion at a dose of 6 mg/kg.⁴ Although rapid infusions offer convenience and potential cost-savings opportunities, there is potential increased risk of infusion-related adverse events. Infusion-related events may include local reactions, such as phlebitis, pain, tenderness, or local erythema, and systemic reactions manifesting as either dermatologic and cardiovascular complications or anaphylaxis. These reactions have been documented with several antimicrobial infusions including ciprofloxacin, amphotericin B, vancomycin, and others agents that stimulate histamine release.⁵ Vancomycin has been classically associated with infusion-related erythroderma or red man’s syndrome. Signs and symptoms of a reaction will often initiate within 1 hour from the start of the infusion.^5,6 For this reason, the preferred infusion rate for vancomycin is no more than 10 mg/min.⁷ In reports to date, local infusion site–related reactions following 2-minute rapid infusion of daptomycin were mild and of short duration, with no systemic flushing reported in the peerreviewed literature. We report a case of an infusion-related reaction with significant flushing secondary to daptomycin following 2-minute IV push that was absent on rechallenge with an extended infusion.     

Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

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Sustained cardiac diastolic changes elicited by ultrafiltration in patients with moderate congestive heart failure: pathophysiological correlates.

OBJECTIVE--To investigate the pathophysiological (cardiac function and physical performance) significance of clinically silent interstitial lung water accumulation in patients with moderate heart failure; to use isolated ultrafiltration as a means of extravascular fluid reabsorption. DESIGN--Echocardiographic, Doppler, chest x-ray evaluations, and cardiopulmonary tests at baseline, soon after ultrafiltration (veno venous extracorporeal circuit), and four days, one month, and three months later. SETTING--University institute of cardiology. SUBJECTS--24 patients with heart failure due to idiopathic dilated cardiomyopathy or ischaemic myocardial disease with sinus rhythm and ejection fraction less than 35%. Twelve were randomised to ultrafiltration and 12 were taken as controls. MAIN OUTCOME MEASURES--Left ventricular systolic function (from ultrasonography); Doppler evaluation of mitral, tricuspid, and aortic flow and echo-Doppler determination of cardiac output; radiological score of extravascular lung water; right and left ventricular filling pressures; oxygen consumption at peak exercise and exercise tolerance time in cardiopulmonary tests. RESULTS--Soon after ultrafiltration (1976 (760) ml of fluid removed) the following was observed: a reduction in radiological score of extravascular lung water (from 15(1) to 9(1)) and of right (from 7.1 (2.3) to 2.3 (1.7) mm Hg) and left (from 17.6 (8.8) to 9.5 (6.4) mm Hg) ventricular filling pressures; an increase in oxygen consumption at peak exercise (from 15.8 (3.3) to 17.6 (2) ml/min/kg) and of tolerance time (from 444 (138) to 508 (134) s); a slight decrease in atrial and ventricular dimensions; no changes in the systolic function of the left ventricle; a reduction of the early to late filling ratio in both ventricles (mitral valve from 2 (2) to 1.1 (1.1)); (tricuspid valve from 1.3 (1.3) to 0.69 (0.18)) and an increase in the deceleration time of mitral and tricuspid flow, reflecting a redistribution of filling to late diastole. Variations in the ventricular filling pattern, lung water content, and functional performance persisted for three months in all cases. None of these changes was detected in the control group. CONCLUSIONS--Reduction of interstitial lung water was probably the mechanism whereby ultrafiltration modified the pattern of filling of the two ventricles and improved functional performance.     

Ku86 preserves chromatin integrity in cells adapted to high NaCl

Cells adapted to high NaCl have many DNA breaks both in cell culture and in the renal inner medulla in vivo; yet they survive, function, and even proliferate. Here, we show that Ku86 is important for maintaining chromosomal integrity despite the continued presence of DNA breaks. The Ku heterodimer is part of DNA-dependent PK (DNA-PK), a complex that contributes by nonhomologous end joining to repair of double-strand breaks. We demonstrate that cells deficient in Ku86, but not cells deficient in DNA-PKcs (the catalytic subunit of DNA-PK), are hypersensitive to high NaCl as manifested by profound inhibition of proliferation, aberrant mitosis, and increased chromosomal fragmentation. Lower eukaryotes, including the soil nematode Caenorhabditis elegans, lack a DNA-PKcs homologue but are able to adapt to high NaCl. We show that cells of C. elegans adapted to high NaCl have many DNA breaks, similar to the mammalian cells adapted to high NaCl. Ku86 mutant C. elegans as well as C. elegans fed with cku86 dsRNA also display hypersensitivity to high NaCl, characterized by a reduced number of progeny and prolonged generation time in high NaCl. We propose that Ku86 ameliorates the effects of high NaCl-induced DNA breaks in adapted cells by supporting alignment of the broken ends of the DNA and thus maintaining integrity of the fragmented chromatin.