Associations between preoperative anaemia and hospital costs following major abdominal surgery: cohort study.

BACKGROUND: Determining the cost-effectiveness and sustainability of patient blood management programmes relies on quantifying the economic burden of preoperative anaemia. This retrospective cohort study aimed to evaluate the hospital costs attributable to preoperative anaemia in patients undergoing major abdominal surgery. METHODS: Patients who underwent major abdominal surgery between 2010 and 2018 were included. The association between preoperative patient haemoglobin (Hb) concentration and hospital costs was evaluated by curve estimation based on the least-square method. The in-hospital cost of index admission was calculated using an activity-based costing methodology. Multivariable regression analysis and propensity score matching were used to estimate the effects of Hb concentration on variables related directly to hospital costs. RESULTS: A total of 1286 patients were included. The median overall cost was US $18 476 (i.q.r.13 784-27 880), and 568 patients (44.2 per cent) had a Hb level below 13.0 g/dl. Patients with a preoperative Hb level below 9.0 g/dl had total hospital costs that were 50.6 (95 per cent c.i. 14.1 to 98.9) per cent higher than those for patients with a preoperative Hb level of 9.0-13.0 g/dl (P < 0.001), 72.5 (30.6 to 128.0) per cent higher than costs for patients with a Hb concentration of 13.1-15.0 g/dl (P < 0.001), and 62.4 (21.8 to 116.7) per cent higher than those for patients with a Hb level greater than 15.0 g/dl (P < 0.001). Multivariable general linear modelling showed that packed red blood cell (PRBC) transfusions were a principal cost driver in patients with a Hb concentration below 9.0 g/dl. CONCLUSION: Patients with the lowest Hb concentration incurred the highest hospital costs, which were strongly associated with increased PRBC transfusions. Costs and possible complications may be decreased by treating preoperative anaemia, particularly more severe anaemia.

Preoperative assessment of retrorectal tumours.

BACKGROUND: Retrorectal tumours present diagnostic and surgical challenges. This study aimed to identify whether preoperative imaging and/or biopsy provide diagnostic accuracy. METHODS: A consecutive series of patients who had undergone excision of a retrorectal tumour were identified from a database (2002-2013). Details of patient demographics, preoperative presentation, imaging, biopsy, surgical procedure, and gross and microscopic pathology were reviewed. Preoperative imaging and/or biopsies were compared with eventual pathology findings. RESULTS: In total, 76 patients were identified, all of whom had undergone preoperative cross-sectional imaging whereas only 22 had preoperative biopsy. Imaging correctly discriminated benign from malignant tumours in 72 of the 76 patients (specificity 97 per cent, sensitivity 88 per cent, positive predictive value 88 per cent and negative predictive value 97 per cent). The corresponding values for preoperative biopsy (benign versus malignant) were 100, 83, 100 and 93 per cent. None of the four patients who were assessed incorrectly as having benign or malignant disease on imaging would have undergone an alternative procedure had this been known before surgery. Preoperative biopsy did not significantly influence patient management, and the absence of preoperative biopsy had no detrimental effect; a definitive preoperative histological diagnosis would not have influenced subsequent management. CONCLUSION: Preoperative imaging was accurate in the assessment of retrorectal tumours, whereas biopsy did not add to the surgical strategy.

Primary melanoma of the cochlea with cerebellopontine extension and leptomeningeal spread.

BACKGROUND: Less than 1 per cent of tumours occurring in the region encompassing the internal auditory canal and the cerebellopontine angle are malignant. Primary central nervous system melanomas arising from this region are exceptionally rare and are often initially misdiagnosed as acoustic neuromas. METHODS: We present a 71-year-old man with acute vestibular disturbance and unilateral hearing loss. Magnetic resonance imaging demonstrated a mass, thought to be a cochlear nerve schwannoma, involving the cochlea and the internal auditory canal. At surgery, a pigmented mass adherent to the facial nerve was visualised, and the observed histopathology was consistent with a malignant melanoma. No extracranial site for the primary tumour was found, suggestive of a primary central nervous system melanoma. RESULTS: Despite surgical resection and adjuvant radiotherapy, the patient re-presented with extensive leptomeningeal disease 16 months later. CONCLUSION: Malignant tumours in the internal auditory canal and cerebellopontine angle region are rare. Early diagnosis and management are aided by recognition of characteristic factors such as a history of prior malignancy, atypical magnetic resonance imaging findings and accelerated audiovestibular symptoms. Despite the presented patient's outcome, total surgical resection with post-operative radiotherapy remains the recommended treatment.

Gender differences on risk factors of non-communicable diseases--a community based cross-sectional study in central Nepal.

BACKGROUND: Non-communicable diseases are the leading causes of death globally, killing more people each year than all other causes combined. As many other developing countries, Nepal is also facing double burden of diseases. The aim of present study was to assess gender wise differences on prevalence of risk factors of non-communicable diseases. METHODS: This was a community based cross sectional study which was based on WHO's STEP approach for surveillance risk factors of non-communicable diseases among males and females. Multi-staged sampling technique was used to get required study sample. Descriptive and inferential statistics were applied to compare the risk factors between two genders. RESULTS: More than two-fifth of male and one-fifth of female respondents were currently using tobacco. The proportion of current alcohol users was found higher among the male respondents (28.6%) than their female counterparts (13.6%) (P<0.001). Only 35 (5.3%) of males and 13 (2.3%) of females were found consuming adequate (≥5 serving) intake of fruits per day. Study revealed that hypertension was slightly higher in male 165 (24.8%) than their female counterparts 111 (19.3%) but differences between two genders were statistically not significant. CONCLUSIONS: The findings of present study suggest that there is high prevalence of risk factors of non-communicable diseases among both sexes in central Nepal. The finding emphasises the need for a focused national strategies targeting to tackle this modern epidemic of non-communicable diseases by incorporating primordial prevention activities to all adult population irrespective to gender.

Clinical profile and outcome of chronic pancreatitis in children.

OBJECTIVE: To evaluate the etiology, presentation, complications and management of chronic pancreatitis in children. DESIGN: Retrospective chart review. SETTING: Gastroenterology department at Christian Medical College and Hospital, Vellore, India between January 2005 and December 2010. PARTICIPANTS: 99 Children (>18 yrs) diagnosed with chronic pancreatitis based on clinical and imaging features. MAIN OUTCOME MEASURES: Etiology, clinical presentation, complications and management of chronic pancreatitis in children. RESULTS: Of 3887 children who attended the Gastroenterology department, 99(2.5%) had chronic pancreatitis, of which 60 (60.6%) were males. In 95(95.9%) patients no definite cause was detected and they were labeled as Idiopathic chronic pancreatitis. All patients had abdominal pain, while 9(9.1%) had diabetes mellitus. Of the 22 children tested for stool fat, 10(45.5%) had steatorrhea. Pancreatic calcification was seen in 69 (69.7%). 68 (71.6%) patients with idiopathic chronic pancreatitis had calcification. Calcific idiopathic chronic pancreatitis was more frequent in males (67.6% vs. 48.1%, P=0.07), and was more commonly associated with diabetes mellitus (13.2% vs. none, P=0.047) and steatorrhea (61.5% vs. 16.7%, P=0.069). Pseudocyst (17.1%) and ascites (9.1%) were the most common complications. All children were treated with pancreatic enzyme supplements for pain relief. 57 patients were followed up. With enzyme supplementation, pain relief was present in 32 (56.1%) patients. Of those who did not improve, 10 underwent endotherapy and 15 underwent surgery. Follow up of 8 patients who underwent endotherapy, showed that 5 (62.5%) had relief. Follow up of 11 patients who underwent surgery showed that only 3 (27%) had pain relief. There was no death. CONCLUSIONS: Idiopathic chronic pancreatitis is the predominant form of chronic pancreatitis in children and adolescents. It can present with or without calcification. The calcific variety is an aggressive disease characterized by early morphological and functional damage to the pancreas.

Partial anterior sacrectomy with nerve preservation to treat locally advanced rectal cancer.

AIM: Most studies that have reported outcomes after composite abdomino-sacral resection for locally advanced/recurrent rectal cancer have involved resections below the S2/3 disc space. Involvement of the sacrum above this level is uncommon and, until recently, was considered a contraindication to resection. METHOD: We report here a surgical technique to deal with high sacral involvement with an anterior approach and maintenance of sacropelvic stability. RESULTS: The operative findings confirmed a locally perforated rectal cancer with an associated abscess cavity and direct invasion into S2. Given the likelihood that a complete dislocation of the sacrum would cause significant neurological damage and pelvic instability without oncological benefit, we opted for a partial high anterior sacrectomy with nerve preservation. The patient made an uncomplicated recovery without neurological deficit and was able to walk with the aid of crutches from postoperative day 3. CONCLUSION: While a high sacral transection is appropriate for some patients with locally advanced/recurrent rectal cancer, operative decisions and options should be tailored to each individual.

Enhanced protection of mice against Japanese encephalitis virus infection by combinations of monoclonal antibodies to glycoprotein E.

In the present study, the protective effect of various combinations of four monoclonal antibodies (MAbs) to glycoprotein E (gpE) of Japanese encephalitis virus (JEV) on the JEV-infected mice was studied. The MAbs were characterized as hemagglutination-inhibition-positive and JEV-specific (Hs). In the protective experiment, mice were first administered single MAbs or their combinations intraperitoneally (i.p.) and 24 hrs later infected with the virus intracerebrally (i.c.). The results showed that single MAbs protected the mice to the extent of 45-65%, while combinations of two or three MAbs gave 85-90% or 100% protection, respectively. The enhanced effect of combinations of several Hs MAbs might be due to the sharing of neutralization epitopes recognized by the Hs MAbs. These results suggested that a combination of at least three epitopes represented by the Hs MAbs should be included in an effective JEV vaccine.

Early death of Japanese encephalitis virus-infected mice administered a neutralizing cross-reactive monoclonal antibody against glycoprotein E.

UNLABELLED: In the present study, the effect of two haemagglutination-inhibition (HAI)-negative auto-reactive (NHA-1 and NHA-2) monoclonal antibodies (MAbs) against glycoprotein E (gpE) of Japanese encephalitis virus (JEV) administered 1 day before or 2 days after intracerebral (i.c.) inoculation of JEV was studied in mice. Of the two MAbs that cross-reacted with West Nile virus (WNV) and histones, the first one (NHA-1) neutralized JEV, while the second one was non-neutralizing. NHA-1 MAb given intraperitoneally (i.p.) 1 day before virus infection induced early death by about 2 days in comparison to controls, whereas mice administered HAI-positive anti-gpE JEV specific MAbs (Hs-1 or Hs-4) were invariably protected. In contrast, MAb NHA-2 failed to produce any effect in mice. Since the similar virus titers were recorded in the brains of experimental and control infected mice, the present results indicated a modification of the biological activity of JEV by the pre-existing MAb NHA-1 that might be leading to an early death of mice. KEYWORDS: Japanese encephalitis virus; neutralizing cross-reactive monoclonal antibody.

Survival of mice immunized with monoclonal antibodies against glycoprotein E of Japanese encephalitis virus before or after infection with Japanese encephalitis, West Nile, and Dengue viruses.

In the present study, the effect of monoclonal antibodies (MAbs) against glycoprotein E (gE) of Japanese encephalitis virus (JEV) strain 733913 administered 1 day before or 2 days after intracerebral (i.c.) challenge with West Nile virus (WNV) strain 68856 or Dengue virus (DENV-2) strain P23085, was studied in mice. Furthermore, two JEV strains belonging to group II (strains 641686 and 691004) that have lost reactivity against virus-specific MAbs were also used in passive immunization experiments. MAbs as ascitic fluids were administered intraperitoneally (i.p.) in mice. Hemagglutination-inhibition- (HAI) positive JEV-specific (Hs-3) MAbs given 2 days after the virus infection showed reduced mortality along with increased survival of mice challenged with WNV or with DENV-2. Also the HAI-positive flavivirus cross-reactive (Hx) MAbs produced a marginal increase in the survival of mice challenged with both JEV strains 641686 and 691004 belonging to the group II. As the MAbs reacting with HAI-positive JEV-specific (Hs) and HAI-negative JEV-specific (NHs) epitopes were neutralizing and protective in mice against JEV strain 733913 challenge, the results indicated presence of the cross-protection phenomenon that might be occurring in some of the localities endemic for the three closely related flaviviruses.

Non-healing gastric ulcer associated with Candida infection.

Candida bezoars of the stomach usually occur after gastric surgery. We report a small Candida mass occurring on a non-healing gastric ulcer in a 40-year-old male non-smoker. The ulcer healed with fluconazole and withdrawal of the proton pump inhibitor.

Protection of mice against experimental Japanese encephalitis virus infections by neutralizing anti-glycoprotein E monoclonal antibodies.

Neutralizing monoclonal antibodies (MAbs) to glycoprotein E (gpE) of Japanese encephalitis (JE) virus given intraperitoneally (i.p.) (0.1 ml of immune ascitic fluid (AF) diluted 1:10 per mouse) to about 4-week-old Swiss mice 1 day prior or 2 days after the virus challenge (100 LD50 of JE virus administered intracerebrally (i.c.)) resulted in a decreased mortality along with an increased survival of the animals as demonstrated by the HAI-positive virus-specific (Hs) MAbs. The protective effect produced by four Hs MAbs was maximum when given 1 day prior the virus challenge, while other, namely HAI-positive flavivirus cross-reactive (Hx) and HAI-negative virus-specific (NHs) MAbs did not produce any effect. Interestingly, one of the two NHs MAbs, namely NHs-1 showed a reduced survival of mice given the MAb 2 days after the virus challenge. Administration of combinations of two or more Hs MAbs may be recommended due to their possible enhanced protection against JE virus infections in mice.

Leishmaniasis diagnosed by liver biopsy: management of two atypical cases.

Two patients presenting with pyrexia of unknown origin were diagnosed as having visceral leishmaniasis based on the presence of Leishmania donovani bodies in liver tissue. Of particular interest is that these two case reports suggest that in patients with pyrexia of unknown origin, a liver biopsy for L. donovani bodies should be considered even when several months have passed since leaving an endemic area, when splenomegaly is absent, when bone marrow examination and serology are not diagnostic, and even when abnormal coagulation necessitates a transjugular liver biopsy.

Effect of tunicamycin on expression of epitopes on Japanese encephalitis virus glycoprotein E in porcine kidney cells.

The effect of tunicamycin (Tm), a glycosylation inhibitor, on the epitopes expressed on Japanese encephalitis virus (JEV) glycoprotein E (gpE) in porcine kidney stable (PS) cells was studied. At Tm concentration of 2 micrograms/ml, the virus-infected cells showed markedly reduced or no reactivity with any of the monoclonal antibodies (MAbs) directed against JEV gpE except NHs-2 and also with polyclonal antibodies (PAbs) directed against JEV. With the increase in Tm concentration to 3 micrograms/ml, a complete loss of the conventionally detected reactivity of the MAbs except NHs-2 was recorded, while the Pabs showed no decrease in their reactivity. However, the MAb NHs-2 and PAbs lost their reactivity when the cells treated with 3 micrograms/ml Tm were stained for epitopes expressed on their surface indicating that glycosylation plays a role in this phenomenon. Tissue culture fluid (TCF) displayed a low virus content in the presence of 3 micrograms/ml Tm, indicating probably a down-regulation of virus maturation inside the cells. Since preM and NS-1 proteins possess besides gpE conserved N-glycosylation sites and play a role in the maturation of JEV, their expression in nascent, i.e. non-glycosylated form might be responsible for the observed low virus content of TCF. Thus, the glycosylation of JEV gpE seems essential for the acquisition of native conformation of its epitopes and their expression in cells.

Loss of virus specific epitopes on JE virus 'E' glycoprotein by acetone treatment.

BACKGROUND & OBJECTIVES: Some Japanese encephalitis (JE) virus strains have been placed in group II based on the loss of reactivity against Hs (H = HI positive; s = JE virus specific) group of monoclonal antibodies (MAbs) in haemagglutination-inhibition (HI) test employing sucrose acetone (SA) extracted antigens. Also acetone-fixation of cells infected with some of the virus strains results in the loss of immunofluorescence (IF) against virus specific MAbs. The present study was undertaken to elucidate the effect of acetone on virus specific haemagglutination (HA) epitopes expressed on 'E' glycoprotein of group II strains of JE virus. METHODS: Porcine kidney (PS) cells were infected with JE virus strains (2 group I Indian strains, 5 group II strains and one neutralization-escape variant of 733913 group I strain). HI and complement fixation (CF) tests were carried out employing both polyethylene glycol (PEG) precipitated and SA extracted antigens of JE virus. RESULTS: Employing PEG precipitated antigens, Indian strain G9473 showed titres ranging from 1:40 to 1:160 against all the four virus specific HsMAbs and strain 641686 (1:160) with one of the four MAbs (Hs-1) by HI test whereas their SA extracted antigens did not react at all. In contrast, CF was positive employing both SA and PEG antigens in the presence of all four HsMAbs. The reactivity shown by PEG antigens in the HI test was confirmed by blocking the HA activity with the respective MAb. SA antigens, though negative in the HI test, were positive by the blocking assay. Interestingly, some of the non-HI MAbs which were negative against SA antigens, showed positive HI reaction with PEG antigens. Also, additional epitopes on Japanese (Yoken), Sri Lankan (691004) and two Indian (755468 and 641686) JE virus strains were detected either by blocking HA or surface IF. INTERPRETATION & CONCLUSIONS: It seems that the acetone treatment might result in HA property of the antigen which is no longer inhibited by an antibody in the HI test. The characterization of such labile and conformation-dependent epitopes is currently been undertaken to elucidate their role either in protection or immunopathogenesis of JE.

An IgM monoclonal antibody to Japanese encephalitis virus recognizing a cross-reactive epitope on nuclear histones.

An IgM class of monoclonal antibody (MAb) raised against 'envelope' (E) glycoprotein of Japanese encephalitis (JE) virus, cross reacted with nuclear histones, in addition to recognizing the viral antigen present in the cytoplasm of infected cells by indirect fluorescent antibody (FA) technique. The experiments on histone depletion by the acid treatment of uninfected PS (porcine kidney) cells, revealed the loss of nuclear immunofluorescence (IF) which was regained after the reconstitution of acid treated cells with histones, prior-to reacting with MAb NHA-2. The IgM MAb recognized specifically the viral antigens expressed on the surface of JE virus infected PS cells by a modified indirect FA. The adsorption of MAb NHA-2 with calf thymus histones (type II-AS) showed a comparative higher drop in the reactivity to JE virus (54.2% reduction) as compared to that against uncomplexed histones (33.3%) by ELISA, thus indicating a higher MAb affinity to the former. In contrast, the adsorption of MAb with chicken RBC nuclei resulted in comparatively more reduction in the reactivity to the uncomplexed histones (52.4% reduction) as against JE virus (37.5%), suggesting that DNA plays some role in modifying and presenting these epitopes. The cross-linkage of epitopes by glutaraldehyde treatment of JE virus antigen and histones showed a 2-fold and higher rise in the MAb reactivity as against those with unfixed or methanol fixed antigens (no cross-linkage), suggesting that the epitope is conformation dependent. Thus, histones seem to share a partial conformational homology with 'E' glycoprotein of JE virus and immune reaction with histones might lead to an autoimmune disorder.

Crohn's disease presenting as pyogenic liver abscess with review of previous case reports.

A 40-yr-old male doctor from India presented with pyogenic liver abscesses as the first manifestation of Crohn's disease. The Crohn's disease itself was limited to the appendix and the adjacent cecum and could be diagnosed only 6 months after the presentation with liver abscess. This single case highlights three unusual features of Crohn's disease, and stresses the importance of meticulous search for a cause for pyogenic liver abscess when it occurs in an otherwise healthy adult.