Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1.

We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R-chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway.     

Neonates as intrinsically worthy recipients of pain management in neonatal intensive care

One barrier to optimal pain management in the neonatal intensive care unit (NICU) is how the healthcare community perceives, and therefore manages, neonatal pain. In this paper, we emphasise that healthcare professionals not only have a professional obligation to care for neonates in the NICU, but that these patients are intrinsically worthy of care. We discuss the conditions that make neonates worthy recipients of pain management by highlighting how neonates are (1) vulnerable to pain and harm, and (2) completely dependent on others for pain management. We argue for a relational account of ethical decision-making in the NICU by demonstrating how an increase in vulnerability and dependence may be experienced by the healthcare community and the neonate’s family. Finally, an ethical framework for decisions around neonatal pain management is proposed, focussing on surrogate decision-making and the importance of compassionate action through both a reflective and an affective empathy. As empathy can be highly motivating against pain, we propose that, in addition to educational programs that raise awareness and knowledge of neonatal pain and pain management, healthcare professionals must cultivate empathy in a collective manner, where all members of the NICU team, including parents, are compassionate decision-makers.

     

The effect of cardiovascular morbidity on clinical response provided by tadalafil in patients with erectile dysfunction

We aimed to investigate the association between erectile dysfunction and severity of cardiovascular morbidity and to assess clinical responses to tadalafil of patients in different cardiovascular risk groups. Between November 2019 and August 2020, a total of 258 male patients aged 45–70 years with ED were included. They were divided into three groups according to the Framingham risk score: low-risk (n: 86, 33.3%), intermediate-risk (n: 103, 39.9%) and high-risk (n: 69, 26.8%). At admission, all domains of the International Index of Erectile Function score were worse in high-risk group compared to other risk groups (p < .001). After a 12-week follow-up, a more significant improvement was observed in all domains of erectile function in all risk groups, but high-risk group had lower sexual scores (p < .001). The lowest rate for complete responsiveness to tadalafil was observed in the high-risk group (37.7%). The rate of failure in complete responsiveness was found to be 4.127 times greater with higher Framingham score and 3.102 times greater with higher erectile dysfunction severity at admission. Our preliminary findings show that more severe sexual disorders are observed in high-risk patients with cardiovascular morbidity. Individualised treatment may be important in high-risk group since they may benefit less from tadalafil, and failure in complete responsiveness can be more common in this group.     

Ultrasonography and erythrocyte distribution width in patients with plantar fasciitis

BackgroundThe measurement of plantar fascia thickness with ultrasonography can be used for both for diagnosis and as a response-to-treatment parameter in plantar fasciitis. Furthermore, with the recent studies, red cell distribution width may be used as an inflammatory marker. Aim of this study is to investigate the association of red cell distribution width and ultrasonography on diagnosis and monitoring of treatment in patients with plantar fasciitis.MethodsClinically diagnosed 102 patients with plantar fasciitis between the dates January 2016 to July 2018 were analysed. Hemogram, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and plantar fascial ultrasonography were obtained on initial evaluation and in 1 month, 2 months and 3 months of the standard nonoperative treatment; American Orthopaedic Foot & Ankle Hindfoot Score (AOFAS) and Visual Analog Scale (VAS) scores were recorded. Posthoc and multivariate logistic regression analysis were used for statistical analysis on SPSS 21.0.ResultsRed cell distribution width was correlated with plantar fascia thickness by the end of the 1 month (r = 0.26, P = .013). Female sex, BMI over 30 kg/m², higher red cell distribution width and higher plantar fascia thickness were associated with plantar fasciitis on initial evaluation. Higher red cell distribution width together with higher plantar fascia thickness were also found to be a risk factor for both on initial evaluation and 1 month after treatment in plantar fasciitis.ConclusionThis study shows that association of red cell distribution width and plantar fascia thickness can be not only a diagnostic predictor but also an indicator of treatment response in plantar fasciitis.Level of clinical evidenceLevel IV     

Selective decontamination of the digestive tract helps prevent bacterial infections in the early postoperative period after liver transplant

In liver transplant (LTx) recipients, gut-associated bacterial and fungal organisms produce significant postoperative morbidity and mortality. We sought to assess the role of selective digestive decontamination (SDD) in preventing postoperative infections in a large single-center cohort of liver recipients transplanted under two non-simultaneous protocols. In 212 consecutive patients transplanted between 1/1/91 and 7/31/92, SDD (gentamicin 80 mg, polymyxin B 100 mg, nystatin suspension 10 mL) was employed, starting after induction of anesthesia and continued until POD 21 (SDD Group). In 157 consecutive patients transplanted between 1/1/93 and 12/31/93, SDD was not used (non-SDD Group). Both groups received IV vancomycin and cefotaxime prophylaxis. All culture-positive infections within the first 30 days post-LTx were recorded and classified as bacterial or fungal. Infection-related mortality (patients who died of infectious complications without any technical complication) was recorded. Groups did not differ in patient demographics, United Network for Organ Sharing (UNOS) status, use of veno-venous bypass, total/warm ischemia, or length of ICU stay. Infections developed in fewer SDD patients (56/212; 26%) than non-SDD patients (69/157; 44%) (p<0.001). The incidence of gram-negative infection was less in the SDD group (11% vs. 26%, p<0. 001) as was gram-positive infection (16% vs. 26%, p<0.001). Among patients who developed infection, there was no difference between groups in infections per patient. Primary graft non-function (PNF) developed in 20 SDD patients (7/20 had infections) and 8 non-SDD patients (6/8 had infections) (p=0.06). There were no differences in incidence of fungal infections or of infection-related mortality between groups. In the SDD group, there were fewer abdominal (p<0. 001), lung (p<0.001), wound (p<0.01), and urinary tract infections (p<0.05). CONCLUSION: Use of SDD in liver recipients early after transplant was associated with significantly fewer infections in the early postoperative period.     

Tacrolimus-associated mutism after orthotopic liver transplantation

BACKGROUND: Mutism/speech apraxia has been well documented as a toxic effect of cyclosporine after liver transplantation but has been reported only rarely with tacrolimus. Brain imaging with magnetic resonance or computed tomography has failed to demonstrate abnormalities in affected patients. METHODS: We present the first example of an acute onset of loss of speech associated with a sudden elevation of serum tacrolimus level after successful orthotopic liver transplantation. We also describe the positron emission tomography (PET) scan of this patient's brain. RESULTS: PET scan imaging of the brain was abnormal, demonstrating decreased metabolism in the posterior temporo-parieto-occipital regions. Statistical probability mapping revealed additional areas of hypometabolism in the cingulate gyrus. CONCLUSIONS: PET scan revealed abnormalities of the brain in a patient with tacrolimus-induced mutism. The cingulate gyrus may play a role in the mutism/speech apraxia syndrome seen with cyclosporine/tacrolimus neurotoxicity.