Mesenteric injury after blunt abdominal trauma.

OBJECTIVE: To present our experience of mesenteric injuries after blunt abdominal trauma. DESIGN: Retrospective study. SETTING: University hospital, Greece. SUBJECTS: 31 patients with mesenteric injuries out of 333 who required operations for blunt abdominal trauma between March 1978 and March 1998. 21 were diagnosed within 6 hours (median 160 min, early group) and in 10 the diagnosis was delayed (median 21 hours, range 15 hours-7 days, delayed group). INTERVENTIONS: Emergency laparotomy. MAIN OUTCOME MEASURES: Mortality, morbidity, and hospital stay. RESULTS: There were no deaths. The diagnosis was confirmed by diagnostic peritoneal lavage in 17/21 patients in the early group whereas 7/10 in the delayed group were diagnosed by clinical examination alone. Most of the injuries (n = 23) were caused by road traffic accidents. 30 patients had injured the small bowel mesentery and 4 the large bowel mesentery. 25 of the 31 patients had associated injuries. There were no complications in the early group, compared with 6 wound infections and 1 case of small bowel obstruction in the delayed group (p < 0.0001). Median hospital stay in the early group was 11 days (range 3-24) compared with 23 days (range 10-61) in the delayed group (p = 0.004). CONCLUSION: Because delay in diagnosis is significantly associated with morbidity and duration of hospital stay we recommend that all patients admitted with blunt abdominal trauma should have a diagnostic peritoneal lavage as soon as possible     

Immunohistochemical Evaluation of 95 Bone Marrow Reactive Plasmacytoses

We histologically and immunohistochemically studied 95 bone marrow (BM) reactive plasmacytoses. Ten biopsies from plasma cell myeloma (PCM) patients served as a control group. In addition, we studied 10 monoclonal gammopathy of undetermined significance (MGUS) cases. Histologically, plasmacytosis varied between 5% and 25% with an interstitial pattern of plasma cell (PC) distribution being characteristically displayed. Immunohistochemically, we did not find any CD56/NCAM nor cyclin D1 expression in all biopsies (95 of 95, 100%), not even a weak, doubtful one; PCs were all polyclonal and CD138 positive. On the contrary, myeloma-associated PCs showed monoclonality for κ- or λ- light chain and strong CD56/NCAM immunoreactivity (8 of 10, 80%); four of them were cyclin D1 positive. Osteoblasts exhibited similar CD56/NCAM expression in both groups. Our data confirm the diagnostic utility of CD56/NCAM in the phenotypic characterization of polyclonal plasma cells, suggesting an important role of this particular immunomarker in the BM trephine study of polyclonal versus neoplastic plasmacytic infiltrations.     

Prevalence,characteristics and outcomes of older patients with hereditary versus wild-type transthyretin amyloid cardiomyopathy

Aims

Transthyretin amyloid cardiomyopathy (ATTR-CM) is often assumed to be associated with wild-type TTR genotype (ATTRwt) in elderly patients (aged ≥70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of transthyretin (TTR) variants among elderly patients diagnosed with ATTR-CM.

Methods and results

Data from consecutive patients over 70 years of age diagnosed with ATTR-CM at the UK National Amyloidosis Centre between January 2010 and August 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all-cause mortality. The study population consisted of 2029 patients with ATTR-CM (median age 79 years at diagnosis, 13.5% females, 80.4% Caucasian). Variant ATTR-CM (ATTRv-CM) was diagnosed in 20.7% (n = 421) of the study population of whom 327 (77.7%) carried V122I, 47 (11.2%) T60A, 16 (3.8%) V30M and 31 (7.3%) other pathogenic TTR variants. During a median (range) follow-up of 29 (12–48) months, ATTRv-CM was associated with increased all-cause mortality compared to ATTRwt-CM, with the poorest survival observed in V122I-associated ATTRv-CM (p < 0.001). Univariable and multivariable logistic regression analyses in those with ATTR-CM showed younger age at diagnosis (odds ratio [OR] 0.85 per year, p < 0.001), female sex (OR 2.73, p < 0.001), Afro-Caribbean ethnicity (OR 65.5, p < 0.001), atrial fibrillation (OR 0.65, p = 0.015), ischaemic heart disease (OR 0.54, p = 0.007), peripheral polyneuropathy (OR 5.70, p < 0.001) and orthostatic hypotension (OR 6.29, p < 0.001) to be independently associated with ATTRv-CM.

Conclusion

Up to 20.7% of elderly patients with ATTR-CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR-CM regardless of age.     

Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival

Background and Aims

Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1 year, are candidates for second-line therapy. The aims of this study are to assess biochemical response pattern and determine the utility of alkaline phosphatase (ALP) at six months as a predictor of insufficient response.

Methods

UDCA-treated patients in the GLOBAL PBC database with available liver biochemistries at one year were included. POISE criteria were used to assess response to treatment, defined as ALP <1.67 × upper limit of normal (ULN) and normal total bilirubin at one year. Various thresholds of ALP at six months were evaluated to predict insufficient response based on negative predictive value (NPV) and that with nearest to 90% NPV was selected.

Results

For the study, 1362 patients were included, 1232 (90.5%) female, mean age of 54 years. The POISE criteria were met by 56.4% (n = 768) of patients at one year. The median ALP (IQR) of those who met POISE criteria compared to those who did not was 1.05 × ULN (0.82–1.33) vs. 2.37 × ULN (1.72–3.69) at six months (p < .001). Of 235 patients with serum ALP >1.9 × ULN at six months, 89% did not achieve POISE criteria (NPV) after one year of UDCA. Of those with insufficient response by POISE criteria at one year, 210 (67%) had an ALP >1.9 × ULN at six months and thus would have been identified early.

Conclusions

We can identify patients for second-line therapy at six months using an ALP threshold of 1.9 × ULN, given that approximately 90% of these patients are non-responders according to POISE criteria.     

Presence of glucocorticoid responsive elements in the mitochondrial genome

Glucocorticoids rapidly affect nuclear RNA synthesis by binding, as hormone-receptor complexes, to Glucocorticoid Responsive Elements (GRE), differently positioned in glucocorticoid inducible genes. Glucocorticoids also affect, within minutes, mitochondrial RNA synthesis. We therefore searched for GREs in the mitochondrial genome of human (H), rat (R) and mouse (M) and found a number of such potential elements as follows: one within the 12s - rRNA gene (H1, R1 and M1) one within (H2), or at the start (R2, M2), of the presumptive protein 1 gene and three within the mouse cytochrome oxidase subunit 1 gene (COX1, COX2 and COX3). The nucleotide sequence of H1, R1 and M1 reveals the possibility of the formation of hairpin structures, stabilized by hydrogen bond formation, between three or four consecutive bases. The presence of potential GREs in the mitochondrial genome suggests an adjustment of mitochondrial metabolic control to the general control mechanisms of the cell.     

2,6-Dichloro-p-phenylenediamine: comparative disposition in male and female rats and mice

2,6-Dichloro-p-phenylenediamine (DPA) was recently reported to induce hepatocellular adenomas and carcinomas in male and female B6C3F1 mice but not in F344 rats. The present investigation of comparative disposition in both sexes of each species was designed to detect species-related variations in DPA disposition that might explain variations in toxicity. Mouse tissues retained higher concentrations of radioactivity at the early time points (15 min and 2 h) than the corresponding rat tissues but were readily cleared at later time points. Elimination of DPA-derived radioactivity by each species was primarily in urine (56-63% of an intravenous dose of 600 mumol/kg body weight) and secondarily in feces (23-31%). Metabolites were qualitatively similar, but varied quantitatively with species. Rats excreted three major and eight minor metabolites in urine, while mice excreted one major and nine minor metabolites. The major metabolite present in mouse urine (61-78% of radioactivity) was approximately two-fold higher than the corresponding major metabolite in rat urine. Efforts to detect covalent binding of DPA and/or metabolites with hepatic DNA indicated no detectable binding in either species. The present study indicates that quantitative variations in disposition and metabolism exist between the two species but does not identify a likely source of species variation in susceptibility to DPA toxicity.