Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency

An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC-->TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg-->Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother.      

Bacterial meningitis in infants: sonographic findings

A retrospective study was performed on 78 patients (newborn to 2 years old) with clinically proved bacterial meningitis. Sonograms were obtained during the acute illness and medical records were reviewed. The spectrum of sonographic features of meningitis included normal scans (30 patients), ventriculomegaly (11 patients), echogenic sulci (31 patients), extra-axial fluid collections (26 patients), abnormal parenchymal echogenicity (9 patients), evidence of ventriculitis (5 patients), and brain abscess (1 patient). In 46 patients, correlation between the sonographic findings and neurologic outcome on clinical follow-up (6 months to 4 years) was made. Findings of abnormal parenchymal echogenicity and/or moderate-to-marked ventriculomegaly were associated with significant neurologic sequelae; however, echogenic sulci and small extra-axial fluid collections did not appear to have any prognostic significance. Twenty-nine of the 78 patients had sonography without clinical indication of complications of meningitis, and in no patient was a significant abnormality found. Our study suggests that sonography is indicated only when there is clinical suspicion of complications.     

Right hemicolectomy anastomotic leak study: a review of right hemicolectomy in the binational clinical outcomes registry (BCOR)

Backgrounds

Surgery remains mainstay management for colon cancer. Post-operative anastomotic leak (AL) carries significant morbidity and mortality. Rates of, and risk factors associated with AL following right hemicolectomy remain poorly documented across Australia and New Zealand. This study examines the Bowel Cancer Outcomes Registry (BCOR) to address this.

Methods

A retrospective cohort study was undertaken of consecutive BCOR-registered right hemicolectomy patients undergoing resection for colon cancer (2007–2021). The primary outcome measure was AL incidence. Clinicopathological data were extracted from the BCOR. Factors associated with AL and primary anastomosis were identified using logistic regression. AL-rate trends were assessed by linear regression.

Results

Of 13 512 patients who had a right hemicolectomy (45.2% male, mean age 72.5 years, SD 12.1), 258 (2.0%) had an AL. On multivariate analysis, male sex (OR 1.33; 95% CI 1.03–1.71) and emergency surgery (OR 1.41; 95% CI 1.04–1.92) were associated with AL. Private health insurance status (OR 0.66; 95% CI 0.50–0.88) and minimally-invasive surgery (OR 0.61; 95% CI 0.47–0.79) were protective for AL. Anastomotic technique (handsewn versus stapled) was not associated with AL (P = 0.84). Patients with higher ASA status (OR 0.47; 95% CI 0.39–0.58), advanced tumour stage (OR 0.56; 95% CI 0.50–0.63), and emergency surgery (OR 0.16; 95% CI 0.13–0.20) were less likely to have a primary anastomosis. AL-rate and year of surgery showed no association (P = 0.521).

Conclusion

The AL rate in Australia and New Zealand following right hemicolectomy is consistent with the published literature and was stable throughout the study period. Sex, emergency surgery, insurance status, and minimally invasive surgery are associated with AL incidence.     

Pilot study of a novel pain management strategy: evaluating the impact on patient outcomes

Background

Our objective was to evaluate the impact of a novel multimodal pain management strategy on intraoperative opioid requirements, postoperative pain, narcotic use, and length of stay.

Methods

Consecutive patients undergoing elective laparoscopic colorectal resection were managed with an experimental protocol. The protocol uses a post-induction, pre-incision bilateral TAP block and local peritoneal infiltration at port sites with long-acting liposomal bupivacaine (20 mL long-acting liposomal bupivacaine, 30 mL 0.25 % bupivacaine, 30 mL saline). Experimental patients were matched on age, body mass index, gender, comorbidity, diagnosis, and procedure to a control group that received no block or local wound infiltration. Both groups followed a standardized enhanced recovery pathway. Demographics, perioperative, and postoperative outcomes were evaluated. The main outcome measures were intraoperative opioids, postoperative pain, opioid use, and length of stay.

Results

Fifty patients were analyzed—25 experimental and 25 controls. Patients were well matched on all demographics. In both cohorts, the main diagnosis was colorectal cancer and primary procedure performed a segmental resection. Operative times were similar (p = 0.41). Experimental patients received significantly less intraoperative fentanyl (mean 158 mcg experimental vs. 299 mcg control; p < 0.01). The experimental group had significantly lower initial (p < 0.01) and final PACU pain scores (p = 0.04) and shorter LOS (3.0 vs. 4.1 days, p = 0.04) compared to controls. Experimental patients trended toward shorter PACU times and lower opioid use and daily pain scores throughout the hospital stay. Postoperative complication and readmission rates were similar across groups. There were no reoperations or mortality.

Conclusions

Our multimodal pain management strategy reduced intraoperative opioid administration. Postoperatively, improvements in PACU time, postoperative pain and narcotic use, and lengths of stay were seen in the experimental cohort. With the favorable finding from the pilot study, further investigation is warranted to fully evaluate the impact of this pain management protocol on patient satisfaction, clinical and financial outcomes.

     

Cytokines and growth factors in keratinocytes and sweat glands in chronic venous leg ulcers. An immunohistochemical study

The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing.