Respiratory disease in Niemann‐Pick type C2 is caused by pulmonary alveolar proteinosis

Griese M, Brasch F, Aldana VR, Cabrera MM, Goelnitz U, Ikonen E, Karam BJ, Liebisch G, Linder MD, Lohse P, Meyer W, Schmitz G, Pamir A, Ripper J, Rolfs A, Schams A, Lezana FJ. Respiratory disease in Niemann‐Pick type C2 is caused by pulmonary alveolar proteinosis. Niemann‐Pick diseases are hereditary neurovisceral lysosomal lipid storage disorders, of which the rare type C2 almost uniformly presents with respiratory distress in early infancy. In the patient presented here, the NPC2 exon 4 frameshift mutation c.408_409delAA caused reduced NPC2 protein levels in serum and lung lavage fluid and the synthesis of an aberrant, larger sized protein of around 28 kDa. Protein expression was strongly reduced also in alveolar macrophages. The infant developed failure to thrive and tachypnea. Lung lavage, computer tomography, and histology showed typical signs of pulmonary alveolar proteinosis with an abnormal intraalveolar accumulation of surfactant as well as macrophages. An NPC2‐hypomorph animal model also showed pulmonary alveolar proteinosis and accumulation of macrophages in the lung, liver, and spleen long before the mice died. Due to the elevation of cholesterol, the surfactant had an abnormal composition and function. Despite the removal of large amounts of surfactant from the lungs by therapeutic lung lavages, this treatment was only temporarily successful and the infant died of respiratory failure. Our data indicate that respiratory distress in NPC2 disease is associated with a loss of normal NPC2 protein expression in alveolar macrophages and the accumulation of functionally inactive surfactant rich in cholesterol.     

Monitoring of macrophage recruitment enhanced by Toll‐like receptor 4 activation with MR imaging in nerve injury

Introduction: Macrophage recruitment is critical for nerve regeneration after an injury. The aim of this study was to investigate whether ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle‐based MRI could be used to monitor the enhanced macrophage recruitment by Toll‐like receptor 4 (TLR4) activation in nerve injury. Methods: Rats received intraperitoneal injections of either lipopolysaccharide (LPS) or phosphate buffered saline (PBS) or no injection (controls) after a sciatic nerve crush injury. After intravenous injection of the USPIOs (LPS and PBS groups) or PBS (control group), MRI was performed and correlated with histological findings. Results: LPS group showed more remarkable hypointense signals on T2*‐weighted imaging and lower T2 values in the crushed nerves than PBS group. The hypointense signal areas were associated with an enhanced recruitment of iron‐loaded macrophages to the injured nerves. Discussion: USPIO‐enhanced MRI can be used to monitor the enhanced macrophage recruitment by means of TLR4 signal pathway activation in nerve injury. Muscle Nerve 58 : 123–132, 2018     

The safety and efficacy of daylight photodynamic therapy in the treatment of actinic keratoses: a systematic review and meta-analysis

Daylight photodynamic therapy (DLPDT) is a novel therapeutic approach for actinic keratoses (AKs). This study aimed to evaluate the safety and efficacy of DLPDT in treating patients with AKs as compared to conventional photodynamic therapy (CPDT). PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for relevant randomized controlled trials (RCTs) published before November 2017, based on the following search terms: “solar keratoses”, “actinic keratoses”, “photodynamic therapy”, “daylight photodynamic therapy”, “conventional photodynamic therapy”, and “randomized”. The complete response rate, patient satisfaction, and patient-reported pain after intervention with DLPDT or CPDT were primarily measured. Sensitivity analysis was conducted to determine the reliability of results. Begg's and Egger's tests were used to assess the likelihood of publication bias. Eight RCTs, comprising a total of 424 patients with AKs treated with DLPDT or CPDT, were included. No significant difference was found between the lesion response rate and the mean lesion response in a comparison of DLPDT and CPDT treatments. Generally, DLPDT was associated with higher patient satisfaction than CPDT. The patients who underwent DLPDT experienced less pain than those who underwent CPDT. Most of our results were of high stability and low sensitivity. Meanwhile, no statistical evidence of publication bias among studies was found under all comparisons. In conclusion, DLPDT is a safe and effective therapy, which could help in selecting the most appropriate therapeutic method for treating AKs and in guiding physicians to optimize treatment strategies.     

SURGERY FOR COMPLETE RECTAL PROLAPSE: A SIMPLIFIED APPROACH

Complete prolapse of rectum (procedentia) is said to occur when the full circumference of the rectal wall is everted through the anus. Numerous techniques have been developed in order to treat procedentia, an uncommon pathology that is managed occasionally by the general surgeon. A simple, safe and effective procedure is recommended for surgeons who treat procedentia recti once in a while. We describe a simple rectopexy procedure which has been used effectively in 38 patients in the last 10 years. In this prospective study we evaluated the results which are comparable to other standard operative techniques in terms of morbidity, anatomic correction and bowel function. This technique is based on sound scientific principles in the aetiopathogenesis of rectal prolapse. This procedure obliterates the abnormally deep cul de sac of rectovesical pouch and supports the anterior rectal wall by suturing it to the bladder base to prevent initiation of sliding herniation of anterior rectal wall, which causes procedentia recti. Posterior dissection fibrosis fixes the posterior rectal wall to the sacrum after healing and restores the normal posterior curve of rectal canal and corrects the pathogenic straightening of rectum which promotes prolapse. Minimal mobilization of rectum is done and lateral ligaments are not dissected hence all attendant complications e.g. impotence, urinary incontinence, constipation etc are avoided. Simplicity, effectiveness, safety and non requirement of prosthetic material makes it an ideal operation suitable for a general surgeon working in the periphery.KEY WORDS: Procedentia, Rectopexy     

Interactions among peripheral perfusion, cardiac activity, oxygen saturation, thermal profile and body position in growing low birth weight infants

Aims: To investigate the correlation between the ‘perfusion index’ (PI) and other commonly used estimates of cutaneous blood flow [heart rate (HR), surface temperatures (ST) and central‐to‐peripheral thermal gradients (C‐P grad)] and to use this new non‐invasive tool to compare differences between prone and supine sleep position in low birth weight (LBW) infants. Methods: Six‐hour continuous recordings of pulse oximetry, cardiac activity and absolute ST from three sites (flank, forearm and leg), along with minute‐to‐minute assessment of behavioural states were performed in 31 LBW infants. Infants were randomly assigned to the prone or supine position for the first 3 h and then reversed for the second 3 h. PI data were correlated with HR and C‐P grad, and compared across sleep positions during quiet sleep (QS) and active sleep (AS). Results: Perfusion index correlated significantly with HR (r² = 0.40) and flank‐to‐forearm thermal gradient (r² = 0.28). In the prone position during QS, infants exhibited higher PI (3.7 ± 0.9 vs. 3.1 ± 0.7), HR (158.4 ± 8.9 vs. 154.1 ± 8.8 bpm), SpO₂ (95.8 ± 2.6 vs. 95.2 ± 2.6%), flank (36.7 ± 0.4 vs. 36.5 ± 0.4°C), forearm (36.1 ± 0.6 vs. 35.5 ± 0.4°C) and leg (35.4 ± 0.7 vs. 34.7 ± 0.7°C) temperatures and narrower flank‐to‐forearm (0.6 ± 0.4 vs. 0.9 ± 0.3°C) and flank‐to‐leg (1.3 ± 0.6 vs. 1.8 ± 0.7°C) gradients, compared to those of the supine position. Similar differences were observed during AS. Conclusion: Perfusion index is a good non‐invasive estimate of tissue perfusion. Prone sleeping position is associated with a higher PI, possibly reflecting thermoregulatory adjustments in cardiovascular control. The effects of these position‐related changes may have important implications for the increased risk for sudden infant death syndrome in prone position.