The value of chemoprophylaxis against Enterococcus species in elective cholecystectomy: a randomized study of cefuroxime vs ampicillin-sulbactam

HYPOTHESIS: Cephalosporins are widely used and considered to be effective as prophylaxis in biliary surgery. Nevertheless, they lack activity against enterococci. We conducted a study to compare the efficacy of ampicillin-sulbactam vs cefuroxime in preventing surgical site infections following elective cholecystectomy. DESIGN: A prospective randomized controlled trial. SETTING: A major tertiary care hospital. PATIENTS: Four hundred eighteen randomized patients (of 549 total), who from July 2002 to August 2004 underwent elective open or laparoscopic cholecystectomy with prospective assessment for development of surgical site infections for 1 month postoperatively. INTERVENTION: A single intravenous dose of 1.5 g of cefuroxime (group A, n = 207) or 3 g of ampicillin-sulbactam (group B, n = 211) was administered during induction of anesthesia. Bile and gallbladder mucosal cultures were taken intraoperatively from all patients. MAIN OUTCOME MEASURE: Number of postoperative surgical site infections. RESULTS: A postoperative surgical site infection was noted in 19 (4.5%) of 418 patients, 18 from group A and 1 from group B (P<.001). In the group that received cefuroxime, 15 (83.3%) of 18 surgical site infections were due to Enterococcus species. Intraoperative bactibilia as well as intraoperative gallbladder rupture were associated with surgical site infections (P<.001). CONCLUSIONS: A single dose of ampicillin-sulbactam favored better compared with cefuroxime for prevention of postoperative surgical site infections due to Enterococcus species after elective cholecystectomy. Ampicillin-sulbactam may be a better agent for antimicrobial prophylaxis in high-risk patients undergoing elective cholecystectomy, especially in a setting where the incidence of enterococcal infections is higher.     

Major depression and risk of depressive symptomatology associated with short-term and low-dose interferon-alpha treatment

OBJECTIVE: The objective of this study is to identify early patients who are at-risk for major depression (MD) induced by interferon-alpha (IFN-alpha) and evaluate the response of depressive symptoms to antidepressants. METHODS: Thirty-six consecutive patients were treated with IFN-alpha. Psychiatric evaluations were performed prior to, and at 1 and 2 months after onset of therapy and upon completion of the study. Diagnoses were made according to DSM-IV criteria, and the severity of depressive symptoms was determined by the Hamilton Depression Rating Scale score (HDRSS). RESULTS: Of the 36 patients studied, 7 (19%) had MD before IFN-alpha treatment, 6 of which manifested a worsening of the depressive symptomatology during treatment. Of the remaining 29 patients, 9 (31%) developed MD during treatment. The median time required for the appearance or worsening of the depressive symptoms was 15 days (range 7-25). The median HDRSS before IFN-alpha in the 36 patients was 3 (range 1-20), whereas after 1 month of therapy, it was 10 (range 1-24; P=.000004). There was a strong positive correlation in the HDRSS before and 1 month after the initiation of treatment (r=.863). Of the 14 patients with a HDRSS of 1-2 before IFN-alpha treatment, only 1 (7%) developed MD, whereas of the 15 patients with a score >3, 8 (53%) developed MD. Antidepressants resulted in a decrease of the HDRSS to the IFN-alpha pretreatment values. CONCLUSION: One third of those treated with IFN-alpha developed MD. The HDRSS before treatment reveals the high- and low-risk patients for developing MD. Psychiatric evaluation should be performed prior to IFN-alpha treatment.     

The reproducibility and prognostic value of serial measurements of heart rate response to regadenoson during myocardial perfusion imaging

Purpose

The heart rate response (HRR, percentage change from baseline) to regadenoson during myocardial perfusion imaging (MPI) can provide incremental prognostic value in patients with known or suspected coronary artery disease. Our purpose was to evaluate the variability and prognostic value of HRR on serial measurements.

Methods

We studied 648 consecutive patients (61?±?11 years, 48 % with diabetes) who underwent two regadenoson MPI studies (16?±?9 months between studies). HRR <30 % was defined as abnormal. All-cause mortality was determined by chart review and verified using the US Social Security Death Master File.

Results

HRR was well correlated between the two studies (intraclass correlation coefficient 0.72, 95 % CI 0.67?–?0.76) with no systematic bias (mean difference 0.88 %, p?=?0.2) or proportional bias (p?=?0.5) by Bland-Altman analysis in all patients and in those with normal MPI on both studies. Of the 308 patients (48 %) with normal baseline HRR (HRR-1), 33 % had developed a blunted HRR on the second MPI study (HRR-2). Older age, male gender, end-stage renal disease, and abnormal baseline left ventricular ejection fraction were independent predictors of a new-onset abnormal HRR. During a mean follow-up of 2.4?±?1.2 years, 55 patients (8.5 %) died. Patients with a blunted HRR-1 had increased mortality risk irrespective of their HRR-2 (p?=?0.9, log-rank test). Among patients with normal HRR-1, a blunted HRR-2 was an independent predictor of all-cause mortality beyond clinical and traditional MPI data (hazard ratio 2.83, 95 % CI 1.14?–?7.03). Finally, patients with a normal HRR-1 and HRR-2 had the lowest event rate, while those with any abnormal HRR had an increased risk of death (hazard ratio 2.5, 95 % CI 1.2?–?5.4).

Conclusion

There was good correlation in the HRR to regadenoson on serial measurements without systematic or proportional biases. Patients with consistently normal HRR had the best prognosis.

     

The Role of Epithelial Cells in the Pathogenesis of Sjögren’s Syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune exocrinopathy that is characterized by periductal mononuclear cell infiltrates in the affected exocrine glands. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. In the recent decade, the application of long-term cultured nonneoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit analysis of the role of these cells in SS pathophysiology. In such studies, cultured SGEC have been demonstrated to express constitutively or inducibly various molecules that are implicated in innate and acquired immune responses, a fact that underscores the inherent capacity of these epithelial cells to induce and promote chronic inflammatory reactions. Furthermore, the parallel analysis of SGEC lines obtained from SS patients and disease controls has revealed the significantly increased constitutive expression of several molecules in cells derived from SS patients. This fact strongly suggests the operation of intrinsic activation mechanisms in the epithelia of patients and further supports the active participation of epithelia in SS pathogenesis.     

A novel study investigating the therapeutic outcome of patients with lytic,mixed and sclerotic bone metastases treated with combined radiotherapy and ibandronate

Purpose To investigate the therapeutic response of patients with different types of bone metastases treated with combined radiotherapy and bisphosphonates. Patients and methods By using computed tomography 52 patients were grouped into groups of lytic, mixed and sclerotic bone lesions. All patients were treated with concomitant radiotherapy and ibandronate (10 monthly cycles) and underwent clinical and radiological evaluations prior to therapy and at 3, 6 and 10 months of follow up. Results At baseline there were statistically significant differences between the three groups for all the evaluated parameters. From 3 months onwards differences were leveled out. Statistically significant improvements were noted at all time points of evaluation for all groups in parameters such as pain (0–10), quality of life (QOL-physical functioning, 0–100) and Karnofsky performance status (KPS). The average pain score for the lytic group was reduced from 8.1 to 1.5 points at 3 months. The corresponding reductions for the mixed and sclerotic groups were from 6.2 to 0.5 and from 4.4 to 0.3 points respectively. Complete pain responses were >76.4% at all time points for all groups. Opioid consumption was also markedly reduced. Overall, the highest clinical response was noted for the lytic group, even though the mean values of pain, QOL and KPS were worse than those of the two other groups at all time points (apart from pain score at 10 months). The percentage of patients of the lytic group experiencing a complete pain response was the least of the three groups during follow up. At 10 months bone density was almost tripled for the lytic and almost doubled for the mixed group. Conclusions Even though the therapeutic outcome for the three groups was similar, the degree of clinical response and reossification differed.     

Opioids modulate constitutive B-lymphocyte secretion

The opioid system plays a major role in immunomodulation, while its action on cells of the immune system may be opioid receptor-mediated or not. Opioid effects on B-lymphocytes are considered as indirect, attributed to an interplay between distinct cell populations. The aim of the present study was to investigate whether opioid agonists (morphine, alpha(S1)-casomorphin and ethylketocyclazocine) may have a direct action on the secretion of antibodies and cytokines by multiple myeloma-derived cell lines and normal CD19+ B-lymphocytes. Our results show that opioids modulate antibody and cytokine secretion by multiple myeloma cells in a cell line-dependent and opioid receptor-independent manner, while they decrease antibody secretion by normal B-lymphocytes. Furthermore, they decrease the proliferation rate of multiple myeloma cells through opioid receptor activation. Our data suggest two different mechanisms of action of opioids, mediated by different signaling pathways: an early non-opioid receptor-related effect, modulating the constitutive immunoglobulin and cytokine secretion, and a long-term receptor-mediated action on cell growth. These data suggest a further opioid implication in the control of humoral immunity.     

Adherence to oral anticoagulation in ischemic stroke patients with atrial fibrillation

BackgroundNon-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved.AimsWe sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF).MethodsWe recruited hospitalised patients (2013–2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA₂DS₂-VASc and SAMe-TT₂R₂ scores with poor adherence.ResultsAmong 396 patients (median age 75.0 years, interquartile range [IQR] 70–80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12–33]; median ARMS score 17 [IQR 17–19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA₂DS₂-VASc and SAMe-TT₂R₂ scores were not associated with poor adherence.ConclusionsAdherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.

KEY MESSAGES

• Adherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke.
• Independent patient-related factors rather than composite scores were associated with poor adherence.
• The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.

     

Parnapimarol and nepetaparnone from Nepeta parnassica

Parnapimarol (1), a new pimarane diterpene, along with nepetaparnone (2) and nepetanudone (3), one new and one previously reported nepetalactone dimer, respectively, were isolated from the dichloromethane extract of the aerial parts of Nepeta parnassica, collected on Mt. Parnassos, Greece. The structures and relative configurations of 1-3 were determined on the basis of their spectroscopic characteristics (1D and 2D NMR, IR, MS). The structure of 2 was confirmed by single-crystal X-ray diffraction analysis. The insecticidal activity of 1-3 against ants and mosquito larvae was also evaluated.     

Presentation and surgical management of xanthogranulomatous cholecystitis

Background: Xanthogranulomatous cholecystitis(XGC) is a rare benign chronic inflammatory disease of the gallbladder that often presents as cholecystitis and most of the times requires surgical management. In addition, distinguishing XGC from gallbladder cancer preoperatively is still a challenge. The aim of the present systematic review was to outline the clinical presentation and surgical approach of XGC. Data sources: The present systematic review was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials(CENTRAL) and Google Scholar databases from inception until June 2020. Results: The laparoscopic cholecystectomy rate(34%) was almost equal to the open cholecystectomy rate(47%) for XGC. An important conversion rate(35%) was observed as well. The XGC cases treated by surgery were associated with low mortality(0.3%), limited intraoperative blood loss(58-270 m L), low complication rates(2%–6%), along with extended operative time(82.6–120 minutes for laparoscopic and 59.6–240 minutes for open cholecystectomy) and hospital stay(3–9 days after laparoscopic and 8.3–18 days after open cholecystectomy). Intraoperative findings during cholecystectomies for XGC included empyema or Mirizzi syndrome. In addition, complex surgical procedures, like wedge hepatic resections and bile duct excision were required during operations for XGC. Conclusions: XGC seemed to be a rare, benign inflammatory disease that presents similar features as gallbladder cancer. The mortality and complication rates of XGC were low, despite the complex surgical procedures that might be required in some cases.     

Signal Detection of Adverse Events Associated with Trastuzumab in a Cohort of Elderly Patients with Breast Cancer

AimUtilization of signal detection methods in longitudinal claims data can improve post-marketing drug surveillance, but to date there has been limited application. The aim of this study is to use 3 approaches, the proportional reporting ratio, Gamma Poisson Shrinker, and tree-based scan statistic in detecting adverse drug events (ADEs) attributed to trastuzumab using an administrative claims dataset.MethodsUsing data from the Texas Cancer Registry and SEER linked to Medicare from 2010 to 2013, we conducted 1:2 propensity score matching. Breast cancer HER2+ patients treated with trastuzumab in addition to standard chemotherapy were matched to HER2– patients treated with standard chemotherapy. Inpatient and outpatient encounters up to 6 months from start of therapy were used to identify adverse events.ResultsA total of 4191 patients were included in the study. Across all methods, use of trastuzumab generated signals on 9 distinct body systems. Cardiomyopathy and heart valve disease were the most consistently detected signals. Clinical review determined that most signals represented known ADEs.ConclusionsWe showed that claims data can be used to complement current ADE monitoring using common data mining methods with propensity score matching. Our analysis identified all expected ADEs associated with trastuzumab, and additional signals of valvular heart disorders.