Pediatric inguinal hernias,are they all the same? A proposed pediatric hernia classification and tailored treatment

Purpose

To propose a new clinical classification for pediatric inguinal hernias modified from a similar classification system for adult inguinal hernia and to propose a tailored repair for each type. The impact of this approach on hernia recurrence will be assessed.

Methods

This prospective and retrospective cross-sectional study was conducted in two tertiary teaching university hospitals in Egypt (Alexandria and Tanta University Children’s Hospitals) from January 2013 to December 2014 on children below 12 years of age with indirect inguinal hernias who were divided into two groups: (a) prospective group I, classified according to our proposed pediatric hernia classification and tailored treatment (PHCTT) into types: pediatric Nyhus 1 (PNI) assigned for herniotomy alone, pediatric Nyhus II (PNII) assigned for herniotomy plus deep ring narrowing, and type pediatric Nyhus III (PNIII) assigned for herniotomy plus posterior wall repair. (b) Retrospective unclassified group II where all cases were assigned to herniotomy alone (open). Data about patient characteristics, assigned hernia type, operative findings, procedures done, and postoperative complications were documented and analyzed by comparing the outcomes of the two groups.

Results

A total of 371 patients were included in this study with 401 hernias (30 bilateral); group I included of 217 patients, while group II included 154 patients. There was a male preponderance in group I (173/217?=?80%) and in group II (130/154?=?85%); the majority in both groups were less than 12 months of age, in group I (132/217?=?66%) and in group II (120/154?=?85%). The median age was 4 months and the median duration of symptoms was 2 months. For group I, PNII hernias formed the predominant cluster making 40% (94/235) followed by PNI hernias making 34.8% (82/235), while PNIII hernias were the least group being 25% (59/235) only. The mean follow-up period was 9.2 months?±?4.8 SD (and 9.1 months?±?2 SD in group II). The pooled recurrence rate was 1.9% (8/401) of the whole series, a weighted mean of the individual recurrence rates of 0% (0/235) of group I and 4.8% (8/166) of group II patients, all males. This difference in the recurrence rates between the two groups was statistically significant (P?=?0.004).

Conclusions

Pediatric inguinal hernias are not the same and there is extreme variation in the presentation regarding the size of the defect. We proposed a nouvelle pediatric hernia classification modified from the original Nyhus classification for adult inguinal hernia with tailored surgical approach to each type (PHCTT). Applying this (PHCTT), it has the benefit of a significant reduction of recurrence rate.

     

Association of atretic left internal mammary graft with internal mammary to pulmonary vasculature fistula: a case series

Left internal mammary artery (LIMA) graft to pulmonary vasculature (PV) fistula is a rare complication of coronary artery bypass surgery (CABG), with only a handful of cases being reported. The fistula in these cases connects to a distal branch of the pulmonary artery. The etiology of these fistulae is uncertain, but is thought to be related to post surgical injury and inflammation leading to adhesions and neorevascularization. The association of an atretic LIMA with these fistulae has not been previously reported. We report six cases of LIMA to PV fistulae that were identified on coronary angiography. All six cases were associated with an atretic LIMA graft. All fistulae were small and did not appear to have significant hemodynamic or clinical consequences. This report describes a previously undescribed association of atretic LIMA graft with small LIMA to PV fistula and discusses possible mechanisms for this association.     

Valganciclovir is an effective prophylaxis for cytomegalovirus disease in liver transplant recipients

Objectives:

Cytomegalovirus (CMV) infection is responsible for significant morbidity and mortality among solid organ transplant recipients. Prophylaxis using valganciclovir (VGCV) in orthotopic liver transplant (OLT) recipients is not approved by the Food and Drug Administration and its use is controversial. This study aimed to evaluate the effectiveness of VGCV in CMV prophylaxis in OLT recipients.

Methods:

We carried out a retrospective, single-centre study including all OLT procedures performed during 2005–2008. Patients with early death (at ≤30 days), without CMV serology or prophylaxis, or with follow-up of <1 year were excluded.

Results:

The overall incidence of CMV disease was 6% (n = 9). The ganciclovir (GCV) and VGCV groups had similar incidences of CMV disease (4.6% vs. 7.0%; P = 0.4) and similar distributions of disease presentation (CMV syndrome vs. tissue-invasive CMV; P = 0.4). Incidences of CMV infection, as well as disease presentation, were similar between the high-risk (CMV D+/R−) and non-high-risk groups (P = 0.16). Although acute cellular rejection occurred more frequently in patients who developed CMV disease (P = 0.005), overall survival in these patients did not differ from that in patients who did not develop CMV infection (P = 0.5).

Conclusions:

Valganciclovir is an effective antiviral for the prevention of CMV disease in liver transplant recipients. Our data support its use in high-risk OLT patients.     

Radial die-wall pressure as a reliable tool for studying the effect of powder water activity on high speed tableting

The effect of moisture as a function of water activity (Aw) on the compaction process is important to understand particle/water interaction and deformation. Studying powder/moisture interaction under pressure with radial die-wall pressure (RDWP) tool was never done. The aim of our study was to use this tool to study this interaction at high compression pressure and speed. Moreover, the effect of changing ejection cam angle (EA) of the machine on ejection force (EF) was investigated. Also, a new tool for prediction of tablet sticking was proposed. Materials with different deformation behaviors stored at low and high moisture conditions were used. Compaction simulation guided by modeling was applied. High Aw resulted in a low residual die-wall pressure (RDP) for all materials, and a high maximum die-wall pressure (MDP) for plastic materials, p < 0.05. This was due to the lubricating and plasticizing effects of water, respectively. However, microcrystalline cellulose showed capping at high Aw and compaction pressure. By increasing compression pressure at high Aw for all materials, effective fall time (EFT) was increased, p < 0.05, showing tendency for sticking. Increasing EA caused an increase of friction and EF for powders, p < 0.05. RDWP was a useful tool to understand particle/moisture interaction under pressure.     

The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors

BACKGROUND

Warfarin is a drug with a narrow therapeutic index and large interindividual variability in daily dosing requirements. Patients commencing warfarin treatment are at risk of bleeding due to excessive anticoagulation caused by overdosing. The interindividual variability in dose requirements is influenced by a number of factors, including polymorphisms in genes mediating warfarin pharmacology, co-medication, age, sex, body size and diet.

AIMS

To develop population pharmacokinetic models of both R- and S-warfarin using clinical and genetic factors and to identify the covariates which influence the interindividual variability in the pharmacokinetic parameters of clearance and volume of distribution in patients on long-term warfarin therapy.

METHODS

Patients commencing warfarin therapy were followed up for 26 weeks. Plasma warfarin enantiomer concentrations were determined in 306 patients for S-warfarin and in 309 patients for R-warfarin at 1, 8 and 26 weeks. Patients were also genotyped for CYP2C9 variants (CYP2C9*1,*2 and *3), two single-nucleotide polymorphisms (SNPs) in CYP1A2, one SNP in CYP3A4 and six SNPs in CYP2C19. A base pharmacokinetic model was developed using NONMEM software to determine the warfarin clearance and volume of distribution. The model was extended to include covariates that influenced the between-subject variability.

RESULTS

Bodyweight, age, sex and CYP2C9 genotype significantly influenced S-warfarin clearance. The S-warfarin clearance was estimated to be 0.144 l h⁻¹ (95% confidence interval 0.131, 0.157) in a 70 kg woman aged 69.8 years with the wild-type CYP2C9 genotype, and the volume of distribution was 16.6 l (95% confidence interval 13.5, 19.7). Bodyweight and age, along with the SNPs rs3814637 (in CYP2C19) and rs2242480 (in CYP3A4), significantly influenced R-warfarin clearance. The R-warfarin clearance was estimated to be 0.125 l h⁻¹ (95% confidence interval 0.115, 0.135) in a 70 kg individual aged 69.8 years with the wild-type CYP2C19 and CYP3A4 genotypes, and the volume of distribution was 10.9 l (95% confidence interval 8.63, 13.2).

CONCLUSIONS

Our analysis, based on exposure rather than dose, provides quantitative estimates of the clinical and genetic factors impacting on the clearance of both the S- and R-enantiomers of warfarin, which can be used in developing improved dosing algorithms.     

Sources of axonal calcium loading during in vitro ischemia of rat dorsal roots

A detailed understanding of injury mechanisms in peripheral nerve fibers will help guide successful design of therapies for peripheral neuropathies. This study was therefore undertaken to examine the ionic mechanisms of Ca2+ overload in peripheral myelinated fibers subjected to chemical inhibition of energy metabolism. Myelinated axons from rat dorsal roots were co-loaded with Ca2+-sensitive (Oregon Green BAPTA-1) and Ca2+-insensitive (Alexa Fluor 594) dextran-conjugated fluorophores and imaged using confocal laser scanning microscopy. Axoplasmic regions were clearly outlined by the Ca2+-insensitive dye, from which axonal Ca2+-dependent fluorescence changes (FCa.ax) were measured. Block of Na+-K+ ATPase (ouabain), opening of Na+ channels (veratridine), and inhibiting energy metabolism (iodoacetate + NaN3) caused a rapid rise in FCa.ax to 96% above control after 30 min. Chemical ischemia (iodoacetate + NaN3) caused a more gradual increase in FCa.ax (54%), which was almost completely dependent on bath Ca2+, indicating that most of the Ca2+ accumulation occurred via influx across the axolemma. Na+ channel block (tetrodotoxin) reduced ischemic FCa.ax rise (14%); however, inhibition of L-type Ca2+ channels (nimodipine) had no effect (60%). In contrast, Na+-Ca2+ exchange inhibition (KB-R7943) significantly reduced ischemic FCa.ax rise (18%). Together our results indicate that the bulk of Ca2+ overload in injured peripheral myelinated axons occurs via reverse Na+-Ca2+ exchange, driven by axonal Na+ accumulation through voltage-gated tetrodotoxin-sensitive Na+ channels. This mechanism may represent a viable therapeutic target for peripheral neuropathies.     

Periodontal care may improve endothelial function

BackgroundPeriodontitis is a chronic, infectious, insidious disease of the tooth-supporting structures that causes a general inflammatory response. The aims of this study were to determine whether periodontitis is associated with endothelial dysfunction leading to cardiovascular events and whether proper management of periodontal disease would improve endothelial function and prevent cardiovascular events in the future.MethodsTwenty-two patients (12 women, 10 men; 40 ± 5 years old) took part in the study. All had severe periodontitis (without systemic disorders) and were all treated conservatively. Thirteen patients returned for a second visit after 3 months of treatment. Endothelial function and periodontal status were evaluated on entry into the study and 3 months following treatment. Ten age-matched, healthy volunteers without periodontal disease served as the control group.ResultsThere was a significant difference between the patient group and the healthy controls: FMD% 4.12 ± 3.96 vs. 16.60 ± 7.86% (p = 0.0000). Periodontitis improved significantly in all 13 patients who completed 3 months of treatment, and their endothelial function improved as well: FMD% 4.12 ± 3.96% vs. 11.12 ± 7.22% (p = 0.007). No difference was found in FID% before and after 3 months of treatment: 20.97 ± 10.66% vs.17.94 ± 6.23% (p = NS).ConclusionsPeriodontitis may be an insidious cause of endothelial dysfunction and cardiovascular events. Treating periodontitis can improve endothelial function and be an important preventive tool for cardiovascular disease.     

Mechanisms of convulsions in eclampsia

Eclampsia is characterized by generalized convulsions in pregnant women with hypertension and proteinuria. Little is known about what triggers the convulsions in this syndrome. The prevailing view is that convulsions are caused by cerebral vasospasm and cerebral edema. However, many important clinical findings argue against cerebral edema or hypertensive encephalopathy as the sole causes of convulsions in eclampsia. The utero-placental ischemia causes the release of certain molecules such as neurokinin B, inflammatory cytokines, endothelins, and tissue plasminogen activator. These molecules stimulate excitatory neuronal receptors and alter neuronal excitability, synaptic transmission, and neuronal survival independent of any vascular effects. Highlighting the neuromodulatory and the convulsive effects of each of these molecules which are elevated in pre-eclampsia, offers a new perspective on the mechanisms of convulsions in eclampsia.