Multi-staged repair of contaminated primary and recurrent giant incisional herniae in the same hospital admission: a proposal for a new approach

Background

Repair of primary and recurrent giant incisional herniae is extremely challenging and more so in the face of surgical field contamination. Literature supports the single- and multi-staged approaches including the use of biological meshes for these difficult patients with their associated benefits and limitations.

Patients and methods

This is a retrospective analysis of a prospective study of five patients who were successfully treated through a multi-staged approach but in the same hospital admission, not previously described, for the repair of contaminated primary and recurrent giant incisional herniae in a district general hospital between 2009 and 2012. Patient demographics including their BMI and ASA, previous and current operative history including complications and follow-up were collected in a secure database. The first stage involved the eradication of contamination, and the second stage was the definitive hernia repair with the new generation-coated synthetic meshes.

Results

Of the five patients, three were men and two women with a mean age of 58 (45–74) years. Two patients had grade 4 while the remaining had grade 3 hernia as per the hernia grading system with a mean BMI of 35 (30–46). All patients required extensive adhesiolysis, bowel resection and anastomoses and wash out. Hernial defect was measured as 204* (105–440) cm², size of mesh implant was 568* (375–930) cm² and the total duration of operation (1st + 2nd Stage) was 354* (270–540) min. Duration of hospital stay was 11* (7–19) days with a follow-up of 17* (6–36) months.

Conclusion

We believe that our multi-staged approach in the same hospital admission (for the repair of contaminated primary and recurrent giant incisional herniae), excludes the disadvantages of a true multi-staged approach and simultaneously minimises the risks and complications associated with a single-staged repair, can be adopted for these challenging patients for a successful outcome (* indicates mean).     

Olanzapine-induced restless leg syndrome: A case report and review of literature

Restless leg syndrome (RLS) is a common disorder causing sleep impairment. Antipsychotics particularly belonging to the first generation are a common cause of RLS. Whereas, RLS induced by olanzapine is rare, there are only a few cases reported earlier. We report a 38-year-old lady suffering from persistent delusional disorder who was prescribed olanzapine. She developed RLS after initiation of olanzapine which improved when switched over to risperidone. This report will caution clinicians about this side effect of a very commonly prescribed antipsychotic drug.KEY WORDS: Olanzapine, restless legs syndrome     

Sarcopenia after induction therapy is associated with reduced survival in patients undergoing esophagectomy for locally-advanced esophageal cancer

BackgroundThe impact of sarcopenia on the outcome of esophageal cancer patients remains unknown in North American populations. The current study aims to investigate if sarcopenia at the time of esophagectomy for locally-advanced esophageal cancer (LAEC) is associated with survival.MethodsPatients who underwent induction therapy followed by esophagectomy for LAEC between 2010–2018 at a single institution were identified. Exclusion criteria included follow-up less than 90 days and distant metastatic disease at the time of surgery. Demographic, treatment, and outcome data were retrospectively collected. Computed tomography (CT) scans following induction therapy were analyzed to calculate skeletal muscle index (SMI). Overall survival (OS) and disease-free survival (DFS) were examined using Kaplan-Meier and Cox Proportional Hazard regression analysis.ResultsOverall, 52 patients met inclusion criteria with a median BMI of 25 (IQR, 22.4–29.1) kg/m² and age of 65 (IQR, 57–70) years. Sarcopenia was present in 75% (39/52) of patients at the time of surgery. Sarcopenic patients had a lower median BMI and higher median age when compared to non-sarcopenic patients. There was no difference in gender, race, stage, operative technique, post-operative complications, or hospital length of stay between sarcopenic and non-sarcopenic patients. With a median follow-up of 24.9 months, patients with sarcopenia at the time of esophagectomy had worse OS [median 24.3 (IQR, 9.9–34.5) vs. 50.9 (IQR, 25.6–50.9) months, P=0.0292] and DFS [median 11.7 (IQR, 6.4–25.8) vs. 29.4 (IQR, 12.8–26.7) months, P=0.0387] compared to non-sarcopenic patients.ConclusionsSarcopenia is associated with reduced overall and DFS in patients undergoing esophagectomy for LAEC.     

Andrographolide inhibits human serum albumin fibril formations through site-specific molecular interactions

Protein misfolding and fibrillation are the fundamental traits in degenerative diseases like Alzheimer''s, Parkinsonism, and diabetes mellitus. Bioactives such as flavonoids and terpenoids from plant sources are known to express protective effects against an array of diseases including diabetes, Alzheimer''s and obesity. Andrographolide (AG), a labdane diterpenoid is prescribed widely in the Indian and Chinese health care systems for classical efficacy against a number of degenerative diseases. This work presents an in depth study on the effects of AG on protein fibrillating pathophysiology. Thioflavin T fluorescence spectroscopy and DLS results indicated concentration dependent inhibition of human serum albumin (HSA) fibrillation. The results were confirmed by electron microscopy studies. HSA fibril formations were markedly reduced in the presence of AG. Fluorescence studies and UV-Vis experiments confirmed further that AG molecularly interacts with HSA at site. In silico molecular docking studies revealed hydrogen bonding and hydrophobic interactions with HSA in the native state. Thus AG interacts with HSA, stabilizes the native protein structure and inhibits fibrillation. The results demonstrated that the compound possesses anti-amyloidogenic properties and can be promising against some human degenerative diseases.

Andrographolide inhibited HSA protein fibrillation through site specific interactions.     

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia

We have investigated the effects of coexpression of protein 4.2 and three protein-4.2 variants with band 3 in the Xenopus oocyte expression system. Normal protein 4.2 increased band-3-specific chloride transport in the oocytes. Protein 4.2 also coimmunoprecipitated with band 3 and colocalized with band 3 at the oocyte plasma membrane. The increase in band-3-mediated chloride transport and coimmunoprecipitation of protein 4.2 required the presence of the N-terminal cytoplasmic domain of band 3. Protein 4.2 also localized to the oocyte plasma membrane in the absence of band 3. The protein-4.2 variants 4.2 Tozeur (R310Q) and 4.2 Komatsu (D175Y) had impaired ability to bind to band 3 and these variants did not localize to the oocyte plasma membrane when expressed on their own or when coexpressed with band 3. Unexpectedly, 4.2 Nippon (A142T) behaved similarly to normal protein 4.2. In the absence of a crystal structure of protein 4.2, we propose a homology model of protein 4.2 based on the structure of the sequence-related protein transglutaminase. Using our results in oocytes and this homology model we speculate how these mutations affect protein 4.2 and result in hereditary spherocytosis.     

Solubilization of the low density lipoprotein receptor

The low density lipoprotein (LDL) receptor was solubilized from membranes of bovine adrenal cortex and cultured human cells by incubation with the nonionic detergent octyl-beta-D-glucoside. Receptor activity released into the 100,000 x g supernatant was assayed by a solid-phase procedure: an aliquot of the soluble extract was removed, the detergent was diluted below its critical micellar concentration, causing the receptor to precipitate as a lipid-protein aggregate; the precipitate was collected by centrifugation and incubated with (125)I-labeled LDL ((125)I-LDL); and the receptor-bound (125)I-LDL was separated from free (125)I-LDL by filtration. The (125)I-LDL binding site that was precipitated from the soluble extract of bovine adrenocortical membranes appeared to be the same as the functional LDL receptor of cultured bovine adrenocortical cells and human fibroblasts. It exhibited high affinity and specificity (affinity for LDL more than 200-fold greater than for acetylated LDL, methylated LDL, or high density lipoprotein), dependence on calcium, and susceptibility to destruction by Pronase. The amount of (125)I-LDL binding activity in solubilized membranes from cultured cells was proportional to the number of receptors on the surface of the intact cells. Thus, the number of solubilized receptors was 1/20th of normal in mutant fibroblasts from a subject with homozygous familial hypercholesterolemia and was 1/4th of normal in human epithelioid carcinoma A-431 cells when they were grown in the presence of 25-hydroxycholesterol plus cholesterol. While in the soluble form in the presence of octyl-beta-D-glucoside, the LDL receptor can be carried through several steps of purification.