Application of the procedural consolidation concept to surgical treatment of children with epidermolysis bullosa: a retrospective analysis

Aim

To assess the efficacy of the procedural consolidation concept (PCC) at reducing the number of sessions of general anesthesia necessary for treating children with epidermolysis bullosa (EB).

Methods

We examined the records of children treated at Children''s Hospital of Zagreb between April 1999 and December 2007. Children treated before the introduction of PCC in January 2005 (n = 39) and after (n = 48) were analyzed in order to determine the effect of PCC on the occurrence of complications, days of hospitalization, and number of hospitalizations.

Results

During the study period, 53 patients underwent 220 sessions of general anesthesia for a total of 743 surgical interventions per session. Before the introduction of PCC (n = 39 patients, 83 sessions), the median number of interventions per session was 2 (range 1-5), and after the introduction of PCC (n = 48 patients, 137 sessions) it was 4 (range 3-7, P < 0.001). After the introduction of PCC, the median number of complications per anesthesia session increased from 2 (range 0-10) to 3 (range 0-10) (P = 0.027), but the median number of complications per surgical procedure decreased from 1 (range 0-10) to 0.6 (range 0-2.5) (P < 0.001). PCC lengthened each anesthesia session from a median of 65 minutes (range 35-655) to 95 minutes (range 50-405), (P < 0.001). Total length of hospitalization was similar before (median 1, range 1-4) and after (median 1, range 1-3) introduction of PCC (P = 0.169). The number of hospitalization days per procedure was 3 times lower after the introduction of PCC (median 0.3, range 0.2-3) than before (median 1, range 0.75-1.7) (P < 0.001).

Conclusion

PCC should be considered an option in the surgical treatment of children with EB.Epidermolysis bullosa (EB) refers to a group of rare genetic disorders characterized by cutaneous and extracutaneous fragility, blistering, and subsequent scaring even after a mild mechanical stress (1). The hallmark feature of inherited EB is mechanical fragility (2). The illness is chronic, degenerative, difficult to treat, and lethal. Although the most common symptom of EB is bullae of skin epithelium, blisters may arise on virtually any mucosal surface (3). Bullae usually heal, leaving atrophic scars. Digital fusion following scar formation is common, rendering the hands useless (3).Traditionally, EB is divided into three major types based on phenotype, mode of inheritance, and genotype (4): EB simplex, junctional EB, and dystrophic EB. More recently, a fourth form, hemidesmosomal EB, was introduced to describe EB in which blisters emerge in the dermal-epidermal circuit. Dystrophic EB is probably the most common form of surgically treated EB (5). Each major EB type has subtypes (4,6,7); two major subtypes of dystrophic EB are dominant dystrophic EB and recessive dystrophic EB. The overall prevalence for inherited EB in the American population is 8.22 per million (8). Prevalence of EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB in the United States of America (USA) is 10.75, 2.04, 2.86, and 2.04 per million, respectively (8). Determining accurate prevalence and incidence data on inherited EB in the USA became possible only after the national EB registry was established in 1986 (9-11). A Croatian national EB registry does not yet exist. According to a study in 1990 on a limited number of EB patients, the prevalence of the Hallopeau-Siemens subtype of recessive dystrophic EB in Croatia was estimated at 9.6 people per million (12).EB has become recognized as a multisystem disorder that poses a number of pre-, peri-, and postoperative challenges (13). Scars, strictures, and stenoses are some of the problems that require surgical treatment (14). In addition, EB affects the oral-gastrointestinal system, creating the need for operative treatment and significantly affecting perioperative care (13).Patients with EB are a high-risk group for anesthesiology because of malnutrition, anemia, hypoproteinemia, dilated cardiomyopathy, and limited mouth opening (15,16).A multidisciplinary team approach to EB treatment is recommended. Preoperative preparation must be individualized, with special attention given to the potential anesthetic problems. When procedures under anesthesia are planned, it is best to coordinate as many surgical procedures as possible to avoid repeated anesthesia (17).Surgical care for EB patients at the Children''s Hospital of Zagreb was for many years quite basic and was not codified into a uniform and standard procedure. In January 2005, the hospital adopted a team approach to treating EB, which led to implementation of a procedural consolidation concept (PCC).The standard approach of repeated sessions of anesthesia with no more than two surgical procedures performed each time (18-20) was replaced with PCC, which implied multiple surgical approaches and procedures during the same session of anesthesia. PCC is based on multidisciplinary team-based treatment planning aimed at reducing the number of times that patients with EB are subjected to general anesthesia. In this study, we analyzed whether PCC was successful at reducing the number of anesthesia sessions without increasing complications or length of hospitalization.     

The cycle of human herpes simplex virus infection: virus transport and immune control

After infection of skin or mucosa, herpes simplex virus enters the sensory nerve endings and is conveyed by retrograde axonal transport to the dorsal root ganglion, where the virus develops lifelong latency. Intermittent reactivation, which is spontaneous in humans, leads to anterograde transport of virus particles and proteins to the skin or mucosa, where the virus is shed and/or causes disease. Immune control of viral infection and replication occurs at the level of skin or mucosa during initial or recurrent infection and also within the dorsal root ganglion, where immune mechanisms control latency and reactivation. This article examines current views on the mechanisms of retrograde and anterograde transport of the virus in axons and the mechanisms of innate and adaptive immunity that control infection in the skin or mucosa and in the dorsal root ganglion--in particular, the role of interferons, myeloid and plasmacytoid dendritic cells, CD4(+) and CD8(+) T cells, and interferon- gamma and other cytokines, including their significance in the development of vaccines for genital herpes.     

Cast Microstructure of a Complex Concentrated Noble Alloy Ag20Pd20Pt20Cu20Ni20

A complex concentrated noble alloy (CCNA) of equiatomic composition (Ag₂₀Pd₂₀Pt₂₀Cu₂₀Ni₂₀–20 at. %) was studied as a potential high—performance material. The equiatomic composition was used so that this alloy could be classified in the subgroup of high—entropy alloys (HEA). The alloy was prepared by induction melting at atmospheric pressure, using high purity elements. The degree of metastability of the cast state was estimated on the basis of changes in the microstructure during annealing at high temperatures in a protective atmosphere of argon. Characterisation of the metallographically prepared samples was performed using a scanning electron microscope (SEM) equipped with an energy dispersive spectrometer (EDS), differential scanning calorimetry (DSC), and X–ray diffraction (XRD). Observation shows that the microstructure of the CCNA is in a very metastable state and multiphase, consisting of a continuous base of dendritic solidification—a matrix with an interdendritic region without other microstructural components and complex spheres. A model of the probable flow of metastable solidification of the studied alloy was proposed, based on the separation of L—melts into L₁ (rich in Ni) and L₂ (rich in Ag). The phenomenon of liquid phase separation in the considered CCNA is based on the monotectic reaction in the Ag−Ni system.     

Effects of α5 GABAA receptor modulation on social interaction,memory, and neuroinflammation in a mouse model of Alzheimer's disease

AimsGABAergic modulation involved in cognitive processing appears to be substantially changed in Alzheimer''s disease (AD). In a widely used 5xFAD model of AD, we aimed to assess if negative and positive allosteric modulators of α5 GABA_A receptors (NAM and PAM, respectively) would affect social interaction, social, object and spatial memory, and neuroinflammation.MethodsAfter 10‐day treatment with PAM, NAM, or solvent, 6‐month‐old transgenic and non‐transgenic 5xFAD mice underwent testing in a behavioral battery. Gene expressions of IL‐1β, IL‐6, TNF‐α, GFAP, and IBA‐1 were determined in hippocampus and prefrontal cortex by qPCR.ResultsPAM treatment impaired spatial learning in transgenic females compared to solvent‐treated transgenic females, and social recognition in transgenic and non‐transgenic males. NAM treatment declined social interaction in transgenic and non‐transgenic males, while had beneficial effect on cognitive flexibility in non‐transgenic males compared to solvent‐treated non‐transgenic males. Transgenic animals have not fully displayed cognitive symptoms, but neuroinflammation was confirmed. NAM reduced proinflammatory gene expressions in transgenic females and astrogliosis in transgenic males compared to pathological controls.ConclusionPAM and NAM failed to exert favorable behavioral effects in transgenic animals. Suppression of neuroinflammation obtained with NAM calls for more studies with GABAergic ligands in amyloid beta‐ and/or tau‐dependent models with prominent neuroinflammation.     

Crystal Structure and Electrical Properties of Ruthenium-Substituted Calcium Copper Titanate

This paper reports a detailed study of crystal structure and dielectric properties of ruthenium-substituted calcium-copper titanates (CaCu₃Ti_4−xRu_xO₁₂, CCTRO). A series of three samples with different stoichiometry was prepared: CaCu₃Ti_4−xRu_xO₁₂, x = 0, 1 and 4, abbreviated as CCTO, CCT3RO and CCRO, respectively. A detailed structural analysis of CCTRO samples was done by the Rietveld refinement of XRPD data. The results show that, regardless of whether Ti⁴⁺ or Ru⁴⁺ ions are placed in B crystallographic position in AA’₃B₄O₁₂ (CaCu₃Ti_4−xRu_xO₁₂) unit cell, the crystal structure remains cubic with Im3¯ symmetry. Slight increases in the unit cell parameters, cell volume and interatomic distances indicate that Ru⁴⁺ ions with larger ionic radii (0.62 Å) than Ti⁴⁺ (0.605 Å) are incorporated in the CaCu₃Ti_4−xRu_xO₁₂ crystal lattice. The structural investigations were confirmed using TEM, HRTEM and ADF/STEM analyses, including EDXS elemental mapping. The effect of Ru atoms share in CaCu₃Ti_4−xRu_xO₁₂ samples on their electrical properties was determined by impedance and dielectric measurements. Results of dielectric measurements indicate that one atom of ruthenium per CaCu₃Ti_4−xRu_xO₁₂ unit cell transforms dielectric CCTO into conductive CCT3RO while preserving cubic crystal structure. Our findings about CCTO and CCT3RO ceramics promote them as ideal tandem to overcome the problem of stress on dielectric-electrode interfaces in capacitors.     

In-hospital mortality of heparin-induced thrombocytopenia in end-stage kidney disease. A retrospective national population-based cohort study

Aim

Heparin induced thrombocytopenia (HIT) and end stage kidney disease (ESKD) are independent conditions associated with increased mortality and morbidity, however, whether ESKD is an independent risk factor for increased mortality in HIT admissions is not well studied. Therefore, we aimed to compare in-hospital mortality in HIT admissions based on their ESKD status.

Methods

This is a retrospective cohort study of HIT hospitalizations aged 18 and older using the 2016–2019 national inpatient sample (NIS) database.

Results

From 2016 to 2019 we had 12 161 admissions for HIT among 28 484 087 total hospitalizations. The annual incidence rate for HIT admissions per 100 000 admissions were: 47, 46, 41.1, and 36.6, respectively (p < .001) in 2016, 2017, 2018, and 2019 respectively. Among HIT admissions, the mean age was 64.3 years, 46.8% were females, 68% were Whites and 16% were Blacks. Black patients have a significantly higher likelihood of in-hospital mortality than White patients (aOR 1.25; 95% CI: 1.06, 1.48; p = .007). Patients who did not have any insurance or self-pay had higher mortality compared to Medicare (aOR 1.64; 95% CI: 1.13, 2.38; p = .009). ESKD status was not associated with higher or lower in-hospital mortality among HIT admissions (aOR 1.002; 95% CI: 0.84, 1.19; p = .981) after adjusting for age, sex, race, and insurance status.

Conclusion

There are no higher or lower odds of in-hospital mortality in the ESKD subgroup in HIT admissions in adults. Decreasing incidence of HIT hospitalizations was seen over the years from 2016 to 2019.