Psychogenic anorexia and non-alcoholic Wernicke's encephalopathy: Complete clinicoradiological recovery with thiamine

Rationale: Prolonged undernutrition may arise out of depression and lead to Wernicke's encephalopathy if timely diagnosis and intervention are missed. Wernicke's encephalopathy is potentially treatable, and appropriate treatment may revert clinical depression and cognitive dysfunction to some extent.Patient's concern: A 69-year-old female who had been taking escitalopram for one year developed tremor, ophthalmoplegia, ataxia, progressive cognitive decline, and convulsions. Diagnosis: Non-alcoholic Wernicke's encephalopathy and hypomagnesemia due to psychogenic anorexia. Interventions: High dose intravenous thiamine and magnesium were supplemented. Outcomes: The patient showed remarkable improvement in neurological complications and even in depressive features. Lessons: Wernicke's encephalopathy should not be ignored in the treatment of depression.     

Obstetric outcomes in cancer survivors

OBJECTIVE: To assess obstetric and neonatal outcomes in women with a prior episode of cancer. METHODS: Data were obtained from a linkage between the Scottish Cancer Registry and routinely collected data from Scottish maternity hospitals. Obstetric outcomes in a first pregnancy which ended between 1980 and 2005 were compared in 917 women with, and 5,496 women without, a previous history of cancer. RESULTS: The mean age at delivery was 29 years (standard deviation 5.66) and 26 years (standard deviation 5.62) in the exposed and unexposed groups respectively (P<.001). Multiple logistic regression showed that cancer survivors had higher rates of postpartum hemorrhage (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.09-2.23) and operative or assisted delivery (abdominal or vaginal) (OR 1.33, 95% CI 1.14- 1.54). Preterm delivery (at less than 37 weeks of gesation) was also found to be higher in this group compared with non-cancer women (OR 1.33, 95% CI 1.01-1.76). CONCLUSION: While largely reassuring to women intending to become pregnant after surviving cancer, the results indicate areas of increased risk that require additional surveillance.     

A survey of clinicians' views on age and access to IVF and the use of tests of ovarian reserve prior to IVF in the United Kingdom

A national survey was performed to determine current practice in the UK in terms of upper age limits for access to in vitro fertilization (IVF) and the use of tests of ovarian reserve. A postal questionnaire was sent to lead clinicians of all assisted conception units (ACU) listed on the Human Fertilisation and Embryology Authority (HFEA) website. Responses were received from 72 out of 84 (85.7%) units. One-fifth of all responders indicated that 20% of all women seeking IVF were more than 40 years old. There was a wide variation in reported upper age limits for access to both NHS- (35 - 50 years) and self-funded (42 - 50 years) IVF. Tests of ovarian reserve were routinely used to exclude women from IVF, but the criteria varied. Few women requested oocyte freezing as a measure for preserving fertility.     

Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia

CD4+ T-cell large granular lymphocyte leukemia (T-LGLL) is a rare subtype of T-LGLL with unknown etiology. In this study, we molecularly characterized a cohort of patients (n = 35) by studying their T-cell receptor (TCR) repertoire and the presence of somatic STAT5B mutations. In addition to the previously described gain-of-function mutations (N642H, Y665F, Q706L, S715F), we discovered six novel STAT5B mutations (Q220H, E433K, T628S, P658R, P702A, and V712E). Multiple STAT5B mutations were present in 22% (5/23) of STAT5B mutated CD4+ T-LGLL cases, either coexisting in one clone or in distinct clones. Patients with STAT5B mutations had increased lymphocyte and LGL counts when compared to STAT5B wild-type patients. TCRβ sequencing showed that, in addition to large LGL expansions, non-leukemic T cell repertoires were more clonal in CD4+ T-LGLL compared to healthy. Interestingly, 25% (15/59) of CD4+ T-LGLL clonotypes were found, albeit in much lower frequencies, in the non-leukemic CD4+ T cell repertoires of the CD4+ T-LGLL patients. Additionally, we further confirmed the previously reported clonal dominance of TRBV6-expressing clones in CD4+ T-LGLL. In conclusion, CD4+ T-LGLL patients have a typical TCR and mutation profile suggestive of aberrant antigen response underlying the disease.Subject terms: Chronic lymphocytic leukaemia, Cancer genetics, T-cell receptor     

Multidrug-resistant Enterobacteriaceae including metallo-β-lactamase producers are predominant pathogens of healthcare-associated infections in an Indian teaching hospital

Purpose: A study was carried out in an Indian teaching hospital in 2009 to detect the rate of surgical site infections (SSI) and peripheral vascular access site infections. Materials and Methods: The study was a point-prevalence study involving over 300 patients. The presence of infection was determined according to the CDC criteria. Swabs were taken from the infected sites and identification and sensitivity were carried out using VITEK® 2 automated system. Characterisation of β-lactamase was carried out at ARRML, Colindale, London. Results: The rate of SSI was 15% for the clean and clean-contaminated categories while that for the dirty contaminated category was 85% (NNIS risk index 0). Cultures yielded definite or probable pathogens from 64% (9/14) of the patients with SSI. In 1/3^rd of the cultures, Staphylococcus aureus was grown and the rest had Enterobacteriaceae, either extended-spectrum β-lactamase (ESBL) producers or Amp-C hyperproducers and, alarmingly, three isolates were positive for newly recognised New Delhi metallo-β-lactamase-1 (NDM-1). In medicine, 87% (n = 99) of the patients had a peripheral IV access device, 55% developed associated phlebitis/infection and, in seven, probable pathogens were isolated (Candida species and Escherichia coli producing ESBL and NDM-1, respectively, Staphylococcus aureus and Enterococcus faecium). All ESBL and metallo-β-lactamase producers were resistant to multiple classes of antimicrobials, the latter being sensitive only to colistin and tigecycline. The study also found that all post-operative patients were on antibiotics, 92% on IV [213 defined daily doses (DDD)/100 post-op patients] limited mainly to the third-generation cephalosporins (26%) and aminoglycosides (24%) and imidazole derivatives (30%). In medicine, 83% (n = 82) were on IV antibiotics (123 DDD/100 bed-days), limited mainly to the third-generation cephalosporins (74%). Conclusion: Indiscriminate use of antibiotics is a major problem predisposing patients to harm by multi-resistant pathogens. Carbapenems were in little use in this hospital, but the selection pressure exerted by cephalosporins and other unrelated classes was sufficient to select NDM-1-producing strains due to co-selection, suggesting a role of single plasmid carrying resistance genes to multiple classes.     

Differential genotypic signatures of Toll-like receptor polymorphisms among dengue-chikungunya mono- and co-infected Eastern Indian patients

Dengue (DENV) and chikungunya (CHIKV) viral infections trigger high patient morbidity and mortality. Mono-/co-infection of these viruses activates innate immune response, triggering Toll-like receptor (TLR) pathways. The present study investigated the differential role of TLR3, 7 and 8 single-nucleotide polymorphisms (SNPs) between mono- and co-infected Eastern Indian patients. Interaction of TLR polymorphic variants with signal peptidase complex (SPC18) was explored which might affect immune signalling against DENV/CHIKV infections. Out of 550 febrile symptomatic patients, 128 DENV-CHIKV co-infected samples were genotyped for eight SNPs of TLR3 (rs3775290-chr4:186083063), TLR7 (rs179008-chrX:12885540, rs5741880-chrX:12869297, rs179010-chrX:12884766, rs3853839-chrX:12889539) and TLR8 (rs5744080-chrX:12919685, rs3764879-chrX:12906578, rs3764880-chrX:12906707) by PCR-RFLP along with 157 healthy individuals. Statistical analysis established genotypic association of TLR SNPs with DENV-CHIKV co-infection, and difference between mono- and co-infected patients and their role in determining high viral load (HVL) during competitive viral replication among co-infected patients. In silico protein-protein docking evaluated interactive effect of TLR variants with SPC18. The findings revealed patients with CC genotypes of TLR7 and 8 SNPs were significantly susceptible towards co-infection, whereas specific genotypes of TLR7 and 8 imparted protection against co-infection. Differential analysis between mono-/co-infected patients revealed distinct genotypic distribution of TLR3, 7 and 8 SNPs. Co-infected patients with TT-rs179010 exhibited DENV-HVL, whereas CHIKV-HVL was detected among patients with other genotypes. Molecular docking of TLR7-rs179008 Q variant and TLR8-rs3764880 V variant with SPC18 generated better free binding energy. This study underlined the importance of TLR7 and 8 SNPs towards mono-/co-infection of DENV/CHIKV, with certain genotypes associated with co-infection susceptibility. Moreover, it suggested a probable role of specific genotypes of TLR7 and 8 polymorphisms imparting high dengue/chikungunya viral load among co-infected patients.

     

Cadaveric study and clinical application of turnover fascial flap for lower-limb defects

Moderately sized defects of various etiologies are encountered frequently in the lower limb. Several reconstructive modalities are available. Majority of them do not meet all the desirable criterion of recipient and donor site. In a search for an optimal procedure, the fascial flap emerged. We found the fascial flap to be suitable and advantageous for many defects. This paper describes the anatomical basis, planning, technique, and application of the fascial flap. To establish the technique, we divided the study in to two parts (a) cadaveric dissection and (b) clinical application. Dissection in 12 fresh cadaver limbs confirmed the location of the perforators of the posterior tibial and peroneal vessels. It also visualised the rich vascular network associated on either side of the deep fascia. The findings also suggested the safe dimension of a retrograde flap which is the key to success. Convinced and encouraged with the above findings, fascial flaps were successfully used for moderately sized defects at various non-weight-bearing areas of lower limb in 20 patients. Out of these, eight were random flaps and 12 were pre-Dopplered perforator flaps. Out of 20, 16 flaps healed uneventfully. In four cases one had complete necrosis while another had partial necrosis. Two cases had complete graft loss although the flap survived. These cases were followed up from 6 months to 2.5 years with an average of 1.5 years. Fascial flaps provide gratifying results in the majority of moderately sized lower-limb defects in non-weight-bearing areas. It meets most of the requirements of reconstruction in a single stage. Therefore, wherever feasible this simple method is justified.     

Intraoperative Duplex Ultrasound Assisted Management of Complex Endoleak

Accurate detection and categorization of endoleaks in failing endografts is crucial in determining their management. The most commonly used imaging modalities are not always definitive. We report a patient with complex mixed endoleaks in whom intraoperative ultrasound resolved diagnostic uncertainty and provided immediate on table confirmation of endoleak exclusion.