The effect of the introduction of the ERAS protocol in laparoscopic total mesorectal excision for rectal cancer.

OBJECTIVE: The aim of the study was to determine whether the introduction of the Enhanced Recovery after Surgery (ERAS) protocol in laparoscopic total mesorectal excision (TME) for rectal cancer offers additional advantages concerning postoperative hospital stay compared to laparoscopy and conventional care. METHODS: A consecutive series of patients that underwent a laparoscopic TME for rectal cancer in a single institution between January 2004 and July 2009 were retrospectively included in this study. The ERAS protocol was introduced in this cohort in January 2007. The study cohort was divided in a conventional care group and an ERAS group. Both groups were compared for primary and secondary outcome measures. The primary outcome measure was postoperative length of hospital stay. RESULTS: Seventy-six patients were included: 43 in the ERAS group and 33 in the conventional care (control) group. Median hospital stay was 7 days (range 2-83 days) in the ERAS group and 10 days (range 4-74 days) in the control group (p = 0.04). Return of bowel function occurred on days 2 and 3 respectively (p < 0.001). There were no significant differences between both groups concerning postoperative complications, readmission rate and reoperations. Thirty-day mortality was absent in both groups. CONCLUSION: These results suggest that the introduction of the ERAS protocol in laparoscopic TME leads to a further reduction in length of hospital stay.

The ERAS protocol reduces the length of stay after laparoscopic colectomies.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) protocol, which is developed to enhance postoperative recovery of patients treated with open colorectal surgery, has been widely adopted. The ERAS protocol has also been introduced in patients treated with laparoscopic colectomy, without data to support its additional value. We investigated whether laparoscopic colectomy in combination with the use of the ERAS protocol leads to a reduction of postoperative length of stay compared to laparoscopic colectomy with conventional care. METHODS: We performed a comprehensive medical record review. Inclusion criteria were patients who had undergone a laparoscopic colectomy at a single center between April 2004 and September 2009 (n = 186). The ERAS protocol had been introduced at the end of 2006. We divided the patients in a pre-ERAS group (n = 77), and an ERAS group (n = 109). We compared the baseline characteristics of both groups. The primary outcome was postoperative length of stay. RESULTS: We did not find significant differences in gender, age, body mass index (BMI), diabetes mellitus (DM), American Society of Anesthesiologists (ASA) classification, and diagnosis and type of surgery between the two groups. Median postoperative length of stay was 6 days (range = 2-28) in the pre-ERAS group and 4 days (range = 2-55) in the ERAS group (P = 0.007). Median return of bowel function was 3 days (range = 1-6) in the pre-ERAS group and 2 days (range = 1-5) in the ERAS group (P < 0.001). We did not find significant differences in postoperative procedure-related complications (wound infection, anastomotic leakage, abscesses), postoperative morbidity, 30-day readmission, 30-day reoperation, and 30-day mortality. CONCLUSIONS: The postoperative length of stay was significantly reduced in the ERAS group without differences in patient outcome. It is suggested that these results are the effect of a combination of the ERAS protocol with laparoscopic colectomy.

High prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on doctors' neckties.

We set out to investigate whether neckties worn by doctors are more likely to be contaminated with Methicillin resistant Staphylococcus aureus (MRSA) compared to neckties worn by preclinical medical undergraduates who have never been exposed to a hospital environment. We discovered that more than half (52%) of neckties worn by doctors were contaminated with Staphylococcus and out of these, 62% of them were identified as MRSA. In contrast, none of the student's ties were contaminated with MRSA. Due to the high prevalence of staphylococcus detected on doctors' neckties, we recommend that health care workers do not wear neckties.

Accuracy of various iron parameters in the prediction of iron deficiency in an acute care hospital.

INTRODUCTION: Iron parameters like serum ferritin and iron saturation are routinely used in diagnosing iron deficiency. However, these tests are influenced by many factors. We aimed to review the accuracy of iron parameters among inpatients in an acute care hospital. MATERIALS AND METHODS: From October 1997 to April 2002, bone marrow aspirate samples from patients on whom concurrent iron studies had been done were analysed. Accuracy of the various iron parameters was analysed using receiver operating characteristic curves. RESULTS: Among 92 bone marrow aspirate samples, 58, 86 and 83 had a concurrent serum ferritin, serum iron and percentage iron saturation done respectively. Serum ferritin is the best marker for predicting the presence of iron deficiency. This is followed by percentage iron saturation and lastly by serum iron. At the most optimal, a serum ferritin of <60 ng/mL has a positive likelihood ratio of 24.35, sensitivity of 69.6%, specificity of 97.1% and positive predictive value of 94.1%. An iron saturation of <7% has a positive likelihood ratio of 21.62, sensitivity of 44.1%, specificity of 98.0% and positive predictive value of 93.8%. Seven out of 50 samples, which had concurrent measurements of iron saturation and serum ferritin, were discordant in indicating the presence of iron deficiency. In 6 cases, the iron saturation was the spurious result. CONCLUSION: A serum ferritin of <60 ng/mL or a percentage iron saturation of <7% is highly predictive of iron deficiency among inpatients in an acute care hospital.

Longevity of antibody responses to a Salmonella typhi-specific outer membrane protein: interpretation of a dot enzyme immunosorbent assay in an area of high typhoid fever endemicity.

The objective of this study was to investigate the longevity of positive dot enzyme immunosorbent assay (dot EIA) results for IgM and IgG to a Salmonella typhi outer membrane protein in Malaysian children with enteric fever. The patients were children one month to 12 years of age with clinical evidence of typhoid fever, positive blood or stool cultures for S. typhi, and/or a positive Widal test result who were admitted over a two-year period to General Hospital (Kota Bharu, Malaysia). These patients received standard inpatient treatment for enteric fever including chloramphenicol therapy for 14 days. Dot EIA tests were performed as part of clinical and laboratory assessments on admission, at two weeks, and then at 3, 6, 9, 12, 15, 18, and 21 months postdischarge. Assessment of the longevity of positive dot EIA IgM and IgG titers was done by Kaplan-Meier analysis. In 94 evaluable patients, 28% were dot EIA IgM positive but IgG negative on admission, 50% were both IgM and IgG positive, and 22% were IgM negative and IgG positive. Mean persistence of IgM dot EIA positivity was 2.6 months (95% confidence interval = 2.0-3.1 months) and that of IgG was 5.4 months (4.5-6.3 months). There were no significant differences between the three subgroups. Thus, positive IgM and IgG results determined by dot EIA within four and seven months, respectively, following documented or suspected enteric fever in a child from an endemic area should be interpreted with caution. In other clinical situations, the dot EIA remains a rapid and reliable aid to diagnosis.

Comparison of once-daily and thrice-daily netilmicin regimens in serious systemic infections: a multicenter study in six Asian countries.

Patients with serious systemic infections admitted to eight medical centers in six Asian countries were treated with 300 mg of netilmicin given once daily (group A: 92 patients) or 100 mg of netilmicin given three times daily (group B: 93 patients). Netilmicin was administered by intramuscular injection or slow intravenous infusion until clinical, laboratory, and bacteriologic measures were normalized and for not more than two additional days. A clinical cure was achieved in 88% of the patients from group A and in 68% from group B. The causative micro-organisms were eliminated or infection site healed in 90% of group A and in 88% of group B. The mean treatment duration was 6.9 days in group A and 8.8 days in group B. Two patients in each group developed symptoms of nephrotoxicity; the pretreatment serum creatinine levels in all four patients were in the high borderline range. No other serious side effects were found. It is concluded that netilmicin administered once daily is safe and more effective than netilmicin administered three times daily.

Cytomegalovirus infection in Penang: a serological survey.

During 1984-1985, a total of 838 sera obtained from individuals of different age groups, mostly blood donors and those whose sera were received for VDRL tests and other serological investigations. The sera were titrated for complement fixing antibodies against cytomegalovirus (Ad169 strain). Three hundred and fifty two (41%) out of 838 sera showed significant antibody titre. The incidence of this virus infection varied form 26% in the age group of 11-20 years to 59% of those above 50 years of age. Geometric mean titre (GMT) was highest (22) in age groups of 11-20 years and those over 50 years indicating active viral infection in these two age groups. GMT was also significantly higher in females in all age groups except in the age group of 21-30 years and those above 50 years, indicating that active viral infection is more common in females.

Acute organophosphorus food poisoning caused by contaminated green leafy vegetables.

An outbreak of food poisoning in which 105 persons from various parts of Singapore were affected was traced to one type of green leafy vegetable (Brassica alboglabra) that had been imported. The clinical symptoms were generally mild and the incubation period short (median 2.5 h). The etiology was confirmed when excessive levels of two organophosphorus pesticides--methamidophos (Tamaron/Monitor; 2.4 ppm-31.7 ppm) and profenofos (Selecron/Curacron; 1.1 ppm-5.4 ppm) were detected in the implicated food, and blood cholinesterase levels of the hospitalized patients were depressed by 26.1%-81.4% based on the lower limit of the reference range. All consignments of the implicated vegetables were immediately sealed and destroyed. Monitoring of imported vegetables for excessive pesticide residues has been enhanced.

Clinico-pathological analysis of myelodysplastic syndromes according to French-American-British classification and international prognostic scoring system.

INTRODUCTION: The aim of this study was to analyse the clinico-pathological features of a cohort of patients with myelodysplastic syndromes (MDS). MATERIALS AND METHODS: The clinical and pathological data of 43 MDS patients over a 3-year period were reviewed. Survival analysis was performed according to the French-American-British (FAB) classification and International Prognostic Scoring System (IPSS) using the Kaplan-Meier method. Selected published studies for comparison were identified from MEDLINE search. RESULTS: The patients were followed up for a median duration of 175 days (range, 2 to 1044 days). The median survival for refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS) has not been reached, but that for refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEB-T) and chronic myelomonocytic leukaemia (CMML) was 250 days, 49 days and 44 days, respectively. The median survival for the low-risk and intermediate-1 IPSS categories has not been reached, while that for the intermediate-2 and high-risk categories was 58 days and 49 days, respectively. The survival analyses, according to the FAB classification and IPSS system, were statistically significant (P <0.05). Comparison of our data with those from neighbouring and Western countries revealed both similarity and disparity. We also noted different cytogenetic information in our cohort of patients. CONCLUSIONS: We found distinctly unique cytogenetic and clinico-pathological characteristics in our MDS patients. However, whether true biological differences exist among MDS patients in different geographies and populations with different genetic and environmental backgrounds require further large multinational study.

Evaluation of the cholera spot test: a chromatographic immunoassay for the rapid detection of cholera antigen.

A chromatographic immunoassay cholera antigen detection kit, the Cholera Spot test, was evaluated. The test was found to be specific with a sensitivity of 10(6) cfu/ml for the direct detection of V. cholerae in simulated stool specimens and 10 cfu/ml in simulated cotton-tipped swab specimens after overnight incubation in alkaline peptone water. This enables early recognition of cholera cases and their contacts so that prevention and control measures can be promptly instituted.

Should we abandon wire-guided localization for nonpalpable breast cancer? A plea for wire-guided localization.

BACKGROUND AND AIMS: To evaluate wire-guided localization for nonpalpable breast cancer regarding procedure and surgery-related outcome in a nonteaching community hospital in the Netherlands. MATERIAL AND METHODS: A consecutive series of 117 patients who were treated with breast-conserving surgery after wire-guided localization for nonpalpable breast cancer between January 2006 and December 2010 was retrospectively analyzed. The patients' digital records were reviewed for patient, radiological, histological, and surgical characteristics. In order to quantify the excess resected tissue, a calculated resection ratio was determined by dividing the total resection volume by the optimal resection volume. The optimal resection volume was defined as a spherical tumor volume with an added 1.0 cm margin. The total resection volume was defined as the corresponding ellipsoid. RESULTS: There were no procedure-related complications. There were two postoperative hemorrhages. Margins were clear in 92.3% of the cases after the first surgical procedure. Eight (6.8%) patients required two operations and one (0.9%) patient required three operations in order to obtain negative margins. Breast conservation was possible in 113 (96.6%) patients. The median calculated resection ratio was 1.87 (range 0.47-14.92). CONCLUSIONS: This study proves that it is possible to obtain excellent results performing breast-conserving surgery for nonpalpable breast cancer regarding margin status, total amount of operations, and the ratio between tumor and resected tissue volume using wire-guided localization as a localization tool.

An unexpected cause for aplastic anaemia in an elderly woman.

Aplastic anaemia is a rare clinical syndrome associated with diminished or absent precursors in the bone marrow. Acquired aplastic anaemia secondary to human immunodeficiency virus (HIV) is very rare. We present a 71-year-old woman with severe aplastic anaemia secondary to HIV infection, which was after extensive exclusion of other causes. She achieved undetectable viral load after 5 months of combination antiretroviral therapy but remains profoundly pancytopenic, complicated by recurrent infectious and bleeding complications. HIV infection should be considered in patients with pancytopenia.

TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties.

TG02 is a novel pyrimidine-based multi-kinase inhibitor that inhibits CDKs 1, 2, 7 and 9 together with JAK2 and FLT3. It dose-dependently inhibits signaling pathways downstream of CDKs, JAK2 and FLT3 in cancer cells with the main targets being CDKs. TG02 is anti-proliferative in a broad range of tumor cell lines, inducing G1 cell cycle arrest and apoptosis. Primary cultures of progenitor cells derived from acute myeloid leukemia (AML) and polycythemia vera patients are very sensitive to TG02. Comparison with reference inhibitors that block only one of the main targets of TG02 demonstrate the benefit of combined CDK and JAK2/FLT3 inhibition in cell lines as well as primary cells. In vivo, TG02 exhibits favorable pharmacokinetics after oral dosing in xenograft models and accumulates in tumor tissues, inducing an effective blockade of both CDK and STAT signaling. TG02 induces tumor regression after oral dosing on both daily and intermittent schedules in a murine model of mutant-FLT3 leukemia (MV4-11) and prolongs survival in a disseminated AML model with wild-type FLT3 and JAK2 (HL-60). These data demonstrate that TG02 is active in various models of leukemia and provide a rationale for the ongoing clinical evaluation of TG02 in patients with advanced leukemias.

SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies.

SB1518 is an innovative pyrimidine-based macrocycle that shows a unique kinase profile with selective inhibition of Janus Kinase-2 (JAK2; IC50=23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) within the JAK family (IC50=1280, 520 and 50 nM for JAK1, JK3 and TYK2, respectively) and fms-like tyrosine kinase-3 (FLT3; IC50=22 nM). SB1518 shows potent effects on cellular JAK/STAT pathways, inhibiting tyrosine phosphorylation on JAK2 (Y221) and downstream STATs. As a consequence SB1518 has potent anti-proliferative effects on myeloid and lymphoid cell lines driven by mutant or wild-type JAK2 or FLT3, resulting from cell cycle arrest and induction of apoptosis. SB1518 has favorable pharmacokinetic properties after oral dosing in mice, is well tolerated and significantly reduces splenomegaly and hepatomegaly in a JAK2(V617F)-driven disease model. SB1518 dose-dependently inhibits intra-tumor JAK2/STAT5 signaling, leading to tumor growth inhibition in a subcutaneous model generated with SET-2 cells derived from a JAK2(V617F) patient with megakaryoblastic leukemia. Moreover, SB1518 is active against primary erythroid progenitor cells sampled from patients with myeloproliferative disease. In summary, SB1518 has a unique profile and is efficacious and well tolerated in JAK2-dependent models. These favorable properties are now being confirmed in clinical studies in patients with myelofibrosis and lymphoma.

Accuracy of serum transferrin receptor levels in the diagnosis of iron deficiency among hospital patients in a population with a high prevalence of thalassaemia trait.

The diagnosis of iron deficiency in hospital patients can be difficult in the presence of inflammation. A raised serum transferrin receptor (sTfR) level is useful as a marker of iron deficiency as it is unaffected by inflammation. However, diseases that cause an increase in erythropoietic activity can also result in a raised sTfR level. In South-East Asia, the prevalence of thalassaemia trait is high. As thalassaemia trait is associated with ineffective erythropoiesis and therefore an increase in the sTfR level, we studied the influence of thalassaemia trait on the diagnosis of iron deficiency in hospital patients. Among 431 patients with different combinations of iron deficiency, alpha- and beta-thalassaemia trait, we found that the sTfR level is an excellent diagnostic test for iron deficiency only in patients without thalassaemia trait. alpha-Thalassaemia trait worsened its diagnostic accuracy and beta-thalassaemia trait rendered it a non-diagnostic test. We conclude that in populations with a high prevalence of thalassaemia trait, the sTfR level is not useful in diagnosing iron deficiency unless the patient's thalassaemia status is known.

Production of myeloid dendritic cells (DC) pulsed with tumor-specific idiotype protein for vaccination of patients with multiple myeloma.

BACKGROUND: Immunotherapy of cancer with DC vaccines has produced encouraging results in clinical trials. Antigen (Ag)-pulsed DC have elicited CD4+ and CD8+ T-cell immunity and tumor regression in humans. However, there is no standard method of DC production. The DC phenotype, number and Ag-loading process used in these studies have varied, making comparisons between trials difficult. METHODS: In the present report a reproducible method was developed for the production of a DC-based vaccine. Monocytes were enriched by adhesion from healthy donor apheresis products and cultured with growth factors for maturation into DC. The cells were loaded with the tumor Ag idiotype proteins from patients with multiple myeloma. DC culture and Ag loading were performed in an automated and closed system. The DC product was characterized for phenotype by flow cytometry and for function in Ag uptake and Ag presentation. RESULTS: These monocyte-derived DC expressed high levels of costimulatory molecules (CD80/86). Ag-pulsed DC functioned to induce allogeneic proliferative lymphocyte responses and Ag-specific cytotoxic T lymphocyte (CTL) responses. The DC viability, phenotype and function were well preserved following prolonged frozen storage. Aliquots from the product of a single DC preparation could be used for sequential vaccinations without batch to batch variability. DISCUSSION: Ag-pulsed DC can be reproducibly generated for clinical use. These standardized methods are now being employed for a clinical trial to evaluate idiotype-pulsed DC vaccine therapy following non-myeloablative transplant for the treatment of multiple myeloma.

A comparison of angiography with oculopneumoplethysmography in carotid artery disease.

Oculopneumoplethysmography (OPPG) is a non-invasive method for the detection of carotid artery disease. In order to evaluate this method an OPPG test was performed routinely on 220 patients who were suspected of cerebrovascular disease. Sixty of these patients, selected on clinical grounds, also underwent angiography and our report deals with this group of patients. They were subdivided in the light of the angiographic findings and the results of the OPPG tests were compared with those of angiography. In 13 patients with a normal angiogram all but one had a normal OPPG test, indicating a specificity of 93%. Three out of 12 patients with a stenosis of less than 60% had an abnormal OPPG test, reflecting hemodynamic alterations in arteries, shown as mildly stenotic by angiography. Thirty-two out of 35 patients with a stenosis of at least 60% or actual occlusion had an abnormal OPPG test indicating a sensitivity of 91%, which increased to 97% with inclusion of carotid compression findings. The hemodynamic significance of the deviating tests in the latter two groups is discussed. OPPG is an easy and simple method of complementing angiography with hemodynamic data in patients with transient ischemic attacks (TIA's) and cerebrovascular accidents (CVA's). It can also be used to screen patients with asymptomatic bruits or vague neurologic complaints, prior to vascular surgery and to follow patients up after carotid endarterectomy.

Rapid serodiagnosis of typhoid fever by dot enzyme immunoassay in an endemic area.

A dot enzyme immunoassay (EIA) using 50-kD outer-membrane proteins (OMPs) of Salmonella typhi was compared with the Widal test for the serodiagnosis of typhoid fever in 109 febrile children admitted to a hospital in an endemic area. In the culture-positive typhoid group, the initial dot EIA was positive in 40 of 42 cases and the initial Widal test was positive in 41. In the culture-negative clinical typhoid group, both the dot EIA and the Widal test were positive in 17 of 18 cases. In the nontyphoidal fever group, the dot EIA was negative in all of 49 cases and the Widal test was negative in 44. With culture used as the gold standard, the dot EIA is as sensitive as the Widal test (95% vs. 98%), has a similar high negative predictive value (96% vs. 98%), and is more specific (75% vs. 67%). In addition, the dot EIA offers the advantages of simplicity, speed, early diagnosis, economy, and flexibility (i.e., other diagnostic tests can be conducted simultaneously).