Effectiveness and safety of colistin among older adults: a systematic review and meta-analysis.

OBJECTIVES: Limited data are available to guide colistin use in older adults (>65 years old). We aimed to assess the effectiveness and safety of colistin in this population. METHODS: Systematic review and meta-analysis of original data from randomized control trials, cohort studies and case-control studies assessing colistin regimens with various comparisons for any infection. Original data were obtained from corresponding authors of original studies. The primary outcome was all-cause 1 month mortality; secondary outcomes included clinical and microbiological outcomes and adverse events, including acute kidney injury. Two independent reviewers screened citations, extracted data and assessed risk of bias. ORs with 95% CIs were pooled. RESULTS: We included 38 publications (41 comparisons) reporting 2857 elderly individuals: 29 studies compared a colistin-based regimen versus another regimen (comparison 1) and 10 compared colistin monotherapy versus colistin combination (comparison 2). No significant difference in 1 month mortality was demonstrated between colistin and comparator (comparison 1, OR 1.13, 95% CI 0.80-1.60; comparison 2, OR 0.99, 95% CI 0.78-1.27). Clinical failure was significantly more likely with colistin-based therapy versus comparator (OR 1.52, 95% CI 1.13-2.06). Acute kidney injury was also significantly more common with colistin-based combinations versus other drugs (OR 3.81, 95% CI 2.14-6.77). CONCLUSIONS: For older adults, colistin-based therapy resulted in no mortality difference, compared with other regimens, for any infection. Clinical failure and acute kidney injury were significantly more common with colistin-based regimens. Close renal function monitoring is needed while using colistin in older adults.

Association of Anemia with Dementia and Cognitive Decline among Community-Dwelling Elderly.

INTRODUCTION: The association of anemia with dementia in elders is controversial. We examined the potential association of anemia with dementia in a large population of elders. METHODS: Historical-prospective registry-based study. Included 36,951 community-dwelling elders (65-113 years) that were followed during 2002-2012. Anemia of all kinds was defined according to Clalit Health Services (CHS) definitions: hemoglobin (HGB) <14 g/dL men, <12 g/dL women; and World Health Organization (WHO): HGB <13 g/dL men, <12 g/dL women. Anemia was categorized as mild (HGB 11-13 g/dL men, 11-12 g/dL women) or moderate-severe (HGB <8-10.9 g/dL men and women). Background data, laboratory values, and diagnosis of dementia and cognitive decline (DCD) were reviewed. RESULTS: During the 10-year follow-up period, DCD was newly diagnosed in 7,180 subjects (19.4%). Subjects with DCD had a higher rate of anemia than those without DCD. Time to development of DCD was 1.5 years shorter in those with than without anemia. On multivariate Cox regression analysis adjusted for age and sex, the hazard ratio (HR) for DCD was 1.45 (95% CI: 1.37-1.54) by CHS and 1.51 (95% CI: 1.41-1.61) WHO anemia criteria. The more severe the anemia, the greater the risk of DCD development (HGB 13-14 g/dL [men only], HR = 1.20 [95% CI: 1.09-1.32]; mild anemia, HR = 1.38 [95% CI: 1.28-1.49]; moderate-severe anemia, HR = 1.64 [CI: 1.41-1.90]). Every decrease in 1 standard deviation of HGB (1.4 g/dL) increased the DCD risk by 15%. A competing risk model has weakened the association of anemia with DCD risk. CONCLUSIONS AND IMPLICATIONS: Anemia in community-dwelling elders appears to be associated with an increased DCD risk in a dose-response manner. Application of the WHO anemia criteria in men may miss patients with mild anemia that places them at DCD risk. Further research should look at anemia as a cause of reversible dementia.

Frail Older Adults with Presymptomatic SARS-CoV-2 Infection: Clinical Course and Prognosis.

BACKGROUND/AIMS: The novel coronavirus SARS-CoV-2 has caused a pandemic threatening millions of people worldwide. This study aimed to describe clinical characteristics, outcomes, and risk factors of SARS-CoV-2-positive, asymptomatic, frail older adults. METHODS: A retrospective cohort study was conducted in 6 designated COVID-19 units, in skilled nursing homes. Subjects were severely frail older adults, positive for SARS-CoV-2, and asymptomatic at the time of their admission in these units. Residents' characteristics and symptoms were obtained via electronic medical records. The primary outcome was a composite of death or hospitalization by day 40. We looked at time to the primary outcome and used Cox regression for a multivariate analysis. RESULTS: During March-November 2020, 849 residents met inclusion criteria. Median age was 84 years. Most were completely dependent for basic activities of daily living and showed cognitive impairment. Six hundred forty-one (75.5%) residents were discharged after considered cured from COVID-19, 125 (14.7%) were hospitalized, and 82 (9.7%) died in the facilities. In survival analysis, 35% reached the primary outcome of death or hospitalization by day 40. Age (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.1-1.4), male gender (HR 1.41; 95% CI: 1.1-1.88), and COPD (HR 1.8; 95% CI: 1.23-2.67) were significant risk factors. CONCLUSIONS: In this large cohort, we report care and prognosis of asymptomatic older adults with major functional or cognitive impairments during the COVID-19 pandemic. Most presymptomatic patients do not develop severe infection, and age stays a predominant risk factor, even in the frailest older adults.

Clinical efficacy and safety of high dose trivalent influenza vaccine in adults and immunosuppressed populations - A systematic review and meta-analysis.

OBJECTIVES: Influenza is associated with significant morbidity and mortality, especially in older and immunocompromised patients. Few data are available on the clinical benefit of high dose trivalent influenza vaccine (TIV). We aimed to assess the clinical efficacy and safety of high dose TIV. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating high dose versus standard dose TIV for prevention of seasonal influenza in adult population. Primary outcome was laboratory-confirmed influenza. Subgroups analyses included older adults and immunocompromised patients. RESULTS: We included 16 trials, 47,857 patients; 10 included older adults and three immunocompromised patients. Laboratory confirmed influenza was significantly reduced with high dose TIV (relative risk 0.76, 95% confidence interval 0.64 to 0.9). This outcome stemmed mainly from one trial in older adults. Specifically, A(H3N2) laboratory confirmed influenza, but not A(H1N1) or B lineages, was reduced. No difference in mortality or hospitalizations was demonstrated. Immunological response was significantly higher with high dose vaccine. Serious adverse events were significantly less common in the high dose group. CONCLUSIONS: High dose TIV lowers the rates of laboratory confirmed influenza, mainly A (H3N2), in older adults vs. standard dose. Further studies should address immunocompromised patients and report clinical outcomes.

Early post-liver transplantation infections and their effect on long-term survival.

BACKGROUND: Infections post-liver transplantation are major drivers for morbidity and mortality. However, the impact of infections within 180 days post-liver transplantation on long-term survival is not clear. METHODS: We present a retrospective cohort of 317 liver transplant patients for whom all infectious episodes were prospectively collected during a mean follow-up of 4.4 years. RESULTS: A total of 143/317 (45%) of patients suffered from any infectious episode during the first 6 months following liver transplantation. Patients with surgical site infections have a reduced survival compared to those with no infection (HR 0.33, 95% CI 0.172-0.636, P = .001), whereas infections from other sources, including pneumonia, UTI, and line-related infections, were not associated with increased mortality. Furthermore, even though the presence of any infection within 30 days or 6 months post-transplantation did not affect survival, more than a single infectious episode per patient was significantly associated with increased mortality (HR 1.70, CI 1.12-2.60, P = .013). In a multivariate analysis, the number of infectious episodes remained statistically significant (HR 1.58, 95% CI 1.03-2.43, P = .035) upon adjustment for other major variables associated with comorbidities and infection risk. CONCLUSIONS: Surgical site infections and the number of infectious episodes within 180 days post-liver transplantation are major determinants of long-term survival among these patients.

Rehabilitation under Social Isolation: Outcomes of Older Individuals with Hip Fractures, Admitted to a Postacute Geriatric Rehabilitation Center, during the COVID-19 Pandemic.

BACKGROUND/AIMS: The novel coronavirus SARS-CoV-2 is the cause of an ongoing pandemic. The highest mortality rate is observed among the older adult population. During the first wave of the pandemic (March-June 2020), following a national health decree demanding that no visitors or family members be allowed in health institutions, our geriatric rehabilitation center closed gates to all visitors from the outside. We aimed to assess the rehabilitation outcomes of older patients with hip fractures in the first pandemic wave, who underwent rehabilitation under complete social isolation from primary care givers and family members. METHODS: This was a retrospective cohort study. It took place at a university-affiliated, major postacute geriatric rehabilitation center. Rehabilitation outcomes measured were discharge functional independence measure (FIM) score and motor FIM score, FIM score change, motor FIM score change, favorable motor FIM effectiveness, length of stay, discharge destination, and home aid at discharge. RESULTS: The study group included 36 patients who were admitted during the first wave of the COVID-19 pandemic (March 1, 2020, to June 30, 2020). The control group comprises 106 individuals with hip fractures who were admitted in the respective time periods during the previous 2 years, that is, March 1, 2018, to June 30, 2018, and March 1, 2019, to June 30, 2019. The facility's occupancy rates were much lower during the first wave of the pandemic in comparison with previous years (78 and 99%, respectively). Patients showed similar demographics and comorbidities, but the social isolation group was more severely deconditioned upon admission. All rehabilitation outcomes were similar between groups. CONCLUSION: According to the findings of this retrospective study, social isolation from family and caregivers did not have a detrimental effect on the rehabilitation outcomes of these patients. More evidence must be gathered and presented on the matter.

Bloodstream infections in the elderly: what is the real goal?

Bloodstream infections (BSI) represent a serious bacterial infection with substantial morbidity and mortality. Population-based studies demonstrate an increased incidence, especially among elderly patients. Controversy exists regarding whether presentation of BSI are different in older patients compared to younger patients; our narrative review of the literature suggests that BSI in elderly patients would probably include one or more of the traditional symptoms/signs of fever, severe sepsis or septic shock, acute kidney injury, and/or leukocytosis. Sources of BSI in older adults are most commonly the urinary tract (more so than in younger adults) and the respiratory tract. Gram-negative bacteria are the most common isolates in the old (~ 40-60% of BSI); isolates from the elderly patient population show higher antibiotic resistance rates, with long-term care facilities serving as reservoirs for multidrug-resistant bacteria. BSI entail significantly higher rates of mortality in older age, both short and long term. Some of the risk factors for mortality are modifiable, such as the appropriateness of empirical antibiotic therapy and nosocomial acquisition of infection. Health-related quality of life issues regarding the elderly patient with BSI are not well addressed in the literature. Utilization of comprehensive geriatric assessment and comprehensive geriatric discharge planning need to be investigated further in this setting and might serve as key for improved results in this population. In this review, we address all these aspects of BSI in old patients with emphasis on future goals for management and research.

Dose-dependent association of proton pump inhibitors use with gastric intestinal metaplasia among Helicobacter pylori-positive patients.

BACKGROUND: Gastric intestinal metaplasia is a pre-cancerous condition associated with multiple factors. OBJECTIVE: We evaluated whether cumulative proton pump inhibitor dose is associated with the diagnosis of gastric intestinal metaplasia while controlling for multiple variables. METHODS: We retrospectively identified patients who underwent upper endoscopy with gastric biopsy between 2005 and 2014. Covariate data retrieved included age, sex, ethnicity, smoking status, Helicobacter pylori status (based on clarithromycin-amoxicillin-proton pump inhibitor issued), cumulative proton pump inhibitor issued within 10 years (quartiles [PPI-Q1-4 ] of daily drug dose), anti-parietal cell antibodies, body mass index and comorbidity index. RESULTS: Of the 14,147 included patients (median age 63.4 years; women 54.4%; Helicobacter pylori-positive 29.0%), 1244 (8.8%) had gastric intestinal metaplasia. Increasing age, Helicobacter pylori infection, smoking, anti-parietal cell antibodies and proton pump inhibitor use were all associated with the diagnosis of gastric intestinal metaplasia. Upper quartiles of cumulative proton pump inhibitor doses (PPI-Q4 and PPI-Q3 vs. PPI-Q1 ) were associated with the diagnosis of gastric intestinal metaplasia: adjusted odds ratios 1.32 (95% confidence interval [CI] 1.111.57) and 1.27 (95% CI 1.07-1.52), respectively, for the whole cohort (Ptotal 0.007, Ptrend 0.013), 1.69 (95% CI 1.23-2.33) and 1.40 (95% CI 1.04-1.89), respectively, for Helicobacter pylori-positive patients (Ptotal 0.004, Ptrend 0.005) and 1.21 (95% CI 0.98-1.49) and 1.20 (95% CI 0.96-1.49), respectively, for Helicobacter pylori-negative patients (Ptotal 0.288, Ptrend 0.018). Upper quartiles of proton pump inhibitor dose were associated with a 5-10-fold increased risk of low-grade dysplasia. CONCLUSIONS: Among Helicobacter pylori-positive patients, proton pump inhibitor use appears to be associated with a dose-dependent increased likelihood of gastric intestinal metaplasia.

Efficacy and safety of ceftazidime/avibactam: a systematic review and meta-analysis.

Background: Ceftazidime/avibactam is approved for complicated intra-abdominal and urinary tract infections (UTIs) based on results from randomized controlled trials (RCTs). Data regarding its effectiveness in treating hospital-acquired infections or resistant pathogens have not been systematically compiled. Methods: A systematic review and meta-analysis including RCTs evaluating ceftazidime/avibactam versus comparator for the treatment of any infection. Primary outcome was 30 day all-cause mortality. Subgroups of hospital-acquired infections and specific resistance phenotypes were planned. Results: Seven publications (eight trials, 4093 patients) were included, reporting a baseline ∼25% of ESBL-carrying Enterobacteriaceae. No significant difference between ceftazidime/avibactam and comparator (mostly carbapenem) was demonstrated for 30 day all-cause mortality, late follow-up mortality and clinical response [relative risk (RR) 1.10, 95% CI 0.70-1.72, P = 0.69; RR 1.23, 95% CI 0.87-1.76, P = 0.25; RR 0.98, 95% CI 0.96-1.01, P = 0.21, respectively, without significant heterogeneity]. Higher microbiological response rate was demonstrated with ceftazidime/avibactam in patients with UTI (RR 1.14, 1.0-1.29, P = 0.05, I2 = 51%). No significant difference in clinical response was demonstrated for patients with ceftazidime-resistant pathogens (RR 1.02, 95% CI 0.94-1.10, P = 0.66, I2 = 0%). Results for other subgroups of resistant pathogens or hospital-acquired infection were not available. Serious adverse events (SAEs) were significantly more common with ceftazidime/avibactam (RR 1.24, 95% CI 1.00-1.54, P = 0.05, I2 = 0%). Conclusions: Ceftazidime/avibactam is clinically and microbiologically as effective as carbapenems for treatment of infections in a setting of ∼25% ESBL-carrying Enterobacteriaceae. Safety of the drug should be further evaluated owing to a higher rate of SAEs compared with carbapenems. Further studies should assess the drug's effectiveness in the treatment of carbapenemase-producing Enterobacteriaceae.

Molecular-based diagnosis of Clostridium difficile infection is associated with reduced mortality.

Polymerase chain reaction (PCR) for the diagnosis of Clostridium difficile infection (CDI) might result in overdiagnosis. The clinical outcomes of symptomatic CDI patients diagnosed by PCR remain uncertain. We aimed to determine whether patients whose diagnosis of CDI was based on PCR had different characteristics and clinical outcomes than those diagnosed by toxin immunoassay. Consecutive CDI patients, hospitalized at Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel, between January 2013 and January 2016, were identified retrospectively and included in the study. Diagnosis of CDI was based on PCR or diagnosis by immunoassay for C. difficile toxin. The main outcome was 30- and 90-day all-cause mortality. The PCR group included 165 patients and the immunoassay group included 157 patients. In comparison to the immunoassay group, patients in the PCR group were more likely to be younger, to be independent, to undergo previous abdominal surgery, and to use laxatives. The 30-day mortality rate in the PCR group was significantly lower than that in the immunoassay group, 29/165 (18%) vs 49/157 (31%), respectively; p = 0.028. On multivariate analysis, PCR diagnosis was associated with reduced mortality, OR 0.48 (95% CI 0.26-0.88). PCR-based diagnosis of CDI is associated with reduced all-cause mortality rates. Further studies are needed to determine the management of patients with discrepant immunoassay and PCR diagnosis of CDI.

Helicobacter pylori infection is positively associated with an increased BMI, irrespective of socioeconomic status and other confounders: a cohort study.

BACKGROUND: Data on the association of Helicobacter pylori infection and BMI are conflicting. The fact that both H. pylori infection and BMI are associated with low socioeconomic status (SES) makes this relationship difficult to characterize. MATERIALS AND METHODS: We aimed to evaluate the association between BMI and H. pylori infection after adjusting for multiple covariates. We analyzed a cohort of 235 107 individuals aged 18 years or older, who performed a C urease breath test (C-UBT), from 2007 to 2014. Data on BMI, age, sex, SES, ethnicity, and medications were extracted from a nationwide population-based database. BMIs were classified according to the WHO recommendations: underweight (<18.5 kg/m), normal weight (18.5-24.9 kg/m), overweight (25-29.9 kg/m), obese class I (30-34.9 kg/m), and obese class II or more (>35 kg/m). STUDY RESULTS: The positivity rate for H. pylori among underweight, normal weight, overweight, and obese class I and class II or more was 55.6, 58.5, 63.0, 64.5, and 65.5%, respectively (P<0.001, Plinear trend 0.007). The association between BMI and H. pylori infection was significant across all SES, sex, ethnicity, and age categories. After adjusting for age, sex, ethnicity, and SES, being overweight and obese class I and class II or more were associated significantly with H. pylori positivity: odds ratio 1.13 [95% confidence interval (CI): 1.11-1.15], 1.14 (95% CI: 1.11-1.17), and 1.15 (95% CI: 1.11-1.19), respectively, P value less than 0.001 for all. CONCLUSION: Among individuals who were referred to a C-UBT by primary care physician, after adjusting for multiple covariates including SES, we found a positive association between H. pylori infection and an increased BMI.

Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel.

We assessed the molecular characteristics and the frequency of mutations in mismatch-repair genes among Bedouin patients with colorectal cancer (CRC) in Israel. Bedouin patients with a diagnosis of CRC at a major hospital in the southern part of Israel were deemed eligible for this study. The primary screening method was immunohistochemical staining for mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2). For subjects with abnormal immunohistochemical staining, we performed microsatellite instability (MSI) analyses, and for tumors with a loss of MLH1 expression we also performed BRAF testing. In MSI high cases we searched further for germline mutations. Of the 24 patients enrolled, four subjects (16.7%) had MSI high tumors: one subject was found to harbor a biallelic PMS2 mutation, one subject had Lynch syndrome (LS) with MSH6 mutation and two subjects had a loss of MLH1/PMS2 proteins/BRAF wild type/normal MLH1 sequence. Ten patients (41.7%) were younger than 50 at the time of diagnosis and none had first degree relatives with CRC. In conclusion, in this cohort of 24 consecutive Arab Bedouins with CRC, one patient was found to harbor a constitutional mismatch repair deficiency, one patient had LS with MSH6 mutation, and two patients had unresolved loss of MLH1/PMS2 proteins/BRAF wild type phenotype.

Adolescent body mass index and risk of colon and rectal cancer in a cohort of 1.79 million Israeli men and women: A population-based study.

BACKGROUND: This study examined the association between the body mass index (BMI) in late adolescence and the risk of colon and rectal cancer. METHODS: This study analyzed a cohort of 1,087,358 Jewish men and 707,212 Jewish women who underwent health examinations at the ages of 16 to 19 years between 1967 and 2002 and were followed by linkage to the national cancer registry up to 2012. Cox regression was used to estimate hazard ratios (HRs) for cancer according to age- and sex-adjusted BMI percentiles from the US Centers for Disease Control and Prevention (overweight, 85th percentile to <95th percentile; obesity, ≥95th percentile). RESULTS: Over a median follow-up of 23 years, 2967 incidence cases of colorectal cancer, including 1977 among men (1403 in the colon and 574 in the rectum) and 990 among women (764 in the colon and 226 in the rectum), were identified. Overweight and obesity were associated with the risk for colon cancer among both men (HR for overweight, 1.53; 95% confidence interval [CI], 1.28-1.84; HR for obesity, 1.54; 95% CI, 1.15-2.06; statistically significant from a BMI of 23.4 kg/m2 [spline analysis]) and women (HR for overweight, 1.54; 95% CI, 1.22-1.93; HR for obesity, 1.51; 95% CI, 0.89-2.57; significant from a BMI of 23.6 kg/m2 ). Obesity, but not overweight, was associated with a risk for rectal cancer among men (HR, 1.71; 95% CI, 1.11-2.65; significant from a BMI of 29.6 kg/m2 ) and women (HR, 2.03; 95% CI, 0.90-4.58; significant from a BMI of 30.6 kg/m2 ). CONCLUSIONS: Being overweight or obese in adolescence was associated with an increased risk of subsequent colon cancers in men and women, whereas obesity was associated with rectal cancer. Cancer 2017;123:4022-30. © 2017 American Cancer Society.

Risk of advanced lesions at the first follow-up colonoscopy after polypectomy of diminutive versus small adenomatous polyps of low-grade dysplasia.

BACKGROUND AND AIMS: The current guidelines for surveillance after polypectomy do not distinguish between diminutive (1-5 mm) and small (6-9 mm) polyps with low-grade dysplasia (LGD). We aimed to evaluate the risk for advanced neoplasia on follow-up colonoscopy. METHODS: We retrospectively analyzed 443 patients whose worst finding at index colonoscopy was polypectomy of 1 to 5 or 6 to 9 mm polyps with LGD and those who underwent a follow-up colonoscopy. RESULTS: During a mean follow-up of 32.0 months (interquartile range 13-48 months), advanced neoplasia was found in 26 patients (5.9%). Among all included patients (n = 443), advanced neoplasia was found in 13 of 310 patients (4.2%) of the 1- to 5-mm group versus 13 of 133 patients (9.8%) of the 6- to 9-mm group (hazard ratio [HR], 3.49; 95% confidence interval [CI], 1.6-7.6). Among the patients with 1 to 2 polyps resected (n = 313), advanced neoplasia was found in 8 of 231 patients (3.5%) of the 1- to 5-mm group versus 8 of 82 patients (9.8%) of the 6- to 9-mm group (HR 3.97; 95% CI, 1.47-10.7). Among the patients with ≥3 polyps resected (n = 130), advanced neoplasia was found in 5 of 79 patients (6.3%) of the 1- to 5-mm group versus 5 of 51 patients (9.8%) of the 6- to 9-mm group (HR 2.4; 95% CI, 0.7-8.36). Fair bowel preparation also was associated with the risk for advanced neoplasia at follow-up (HR 3.87, 95% CI, 1.70-8.82). CONCLUSIONS: Our findings suggest that among patients with up to 9-mm adenomatous polyps, a polyp size of 6 to 9 mm, >2 polyps, and fair bowel preparation are associated with advanced neoplasia.

Patients' Age Rather Than Model of End-Stage Liver Disease Score Predicts Survival After Liver Transplantation.

BACKGROUND: The model of end-stage liver disease (MELD) score is the standard tool for prioritizing patients awaiting liver transplantation. There is currently no definite high cutoff score reflecting disease severity that might exclude patients from transplantation. Furthermore, the age limit that used to disqualify patients from eligibility to transplantation was recently withdrawn in several countries. AIMS: The aims of this study were to assess the effects of MELD score and age at time of transplantation on patients' short- and long-term survival. METHODS: We conducted a retrospective single-center study on a cohort of patients transplanted for the first time due to non-fulminant liver failure. RESULTS: Four hundred and seventeen patients (mean age 50.2 years, 63% males) who underwent liver transplantation for the first time were included. Both higher patients' and donors' age were significantly associated with increased long-term mortality (p = 0.007, 95% CI 1.006-1.038 for patient age, p = 0.02, 95% CI 1.002-1.023 for donor age). Patients' age remained significantly associated with survival at 1 year post-transplantation, as well. We found no association between higher MELD score at transplantation and long-term mortality (p = 0.189, 95% CI 0.99-1.051) irrespective of patients' age. Specifically, when patients were divided according to their MELD score at transplantation (MELD < 15, MELD 15-25 and MELD > 25), no significant differences in long-term survival were detected between these three subgroups. Results did not differ significantly in a subgroup analysis of patients without hepatocellular carcinoma at the time of transplantation. CONCLUSIONS: Patients' and donors' age rather than patients' MELD score at transplantation determine survival following liver transplantation.

Risk factors for short- and long-term mortality in very old patients with Clostridium difficile infection: A retrospective study.

AIM: Most cases of Clostridium difficile infections (CDI) occur in patients aged 65 years and older. Older age is associated with increased mortality. Risk factors for mortality in patients aged 80 years and older are not well recognized. METHODS: We analyzed retrospective data including 184 patients aged 80 years and older hospitalized with CDI during 2009-2014. We aimed to delineate risk factors for short- and long-term mortality. RESULTS: The 30-day mortality was 33.2%; 1-year mortality was 64.7%. Median survival was 110 days (interquartile range 24-655 days). All four patients who underwent colectomy died. Risk factors for 30-day mortality in multivariate analysis were diabetes mellitus, low albumin and therapy other than metronidazole monotherapy, the latter probably reflecting higher severity of disease rather than a true predictor of mortality. Risk factors for long-term mortality analyzed in Cox regression were albumin ≤2.5 g/dL (HR 0.58, 95% CI 0.395-0.850), presentation with sepsis (HR 0.597, 95% CI 0.408-0.873), a non-independent activities of daily living baseline status (HR 0.460, 95% CI 0.236--0.897) and Charlson score (HR 0.867, 95% CI 0.801-0.938). None of the traditional severity indices for CDI (such as leukocytosis or creatinine increase) proved to be predictors of mortality over the age of 80 years. CONCLUSIONS: The prognosis of old patients with CDI is dismal. Considering the high mortality, efforts to prevent CDI should be first priority in patients aged 80 years and older. Assessment of albumin levels should be part of the evaluation at presentation and considered when choosing treatment, rather than standard severity indexes for CDI. Geriatr Gerontol Int 2017; 17: 1378-1383.

Anthropometric measures and prevalence trends in adolescents with coeliac disease: a population based study.

OBJECTIVES: To investigate the impact of coeliac disease (CD) diagnosis on anthropometric measures at late adolescence and to assess trends in the prevalence of diagnosed CD over time. DESIGN: A population based study. PATIENTS: Prior to enlistment, at the age of 17 years, most of the Israeli Jewish population undergoes a general health examination. Subjects' medical diagnoses are entered into a structured database. INTERVENTIONS: The enlistment database was thoroughly searched for CD cases between the years 1988 and 2015. Medical records of 2 001 353 subjects were reviewed. MAIN OUTCOME MEASURES: Anthropometric measures at the age of 17 years. RESULTS: Overall, 10 566 CD cases (0.53%) were identified and analysed. Median age at data ascertainment was 17.1 years (IQR, 16.9-17.4). Multivariable analysis demonstrated that boys with CD were leaner (Body Mass Index 21.2±3.7 vs 21.7±3.8, p=0.02) while girls with CD were shorter (161.5±6 cm vs 162.1±6 cm, p=0.017) than the general population. The prevalence of diagnosed CD increased from 0.5% to 1.1% in the last 20 years with a female predominance (0.64% vs 0.46%). CD prevalence was significantly lower in subjects of lower socioeconomic status and those of African, Asian and former Soviet Union origin. CONCLUSIONS: Adolescent boys with CD were leaner and girls with CD were shorter compared with the general population. However, the clinical relevance of the small differences suggests that when CD is diagnosed during childhood, final weight and height are not severely impaired. Our cohort reinforces the observed increase in diagnosed CD.

Immunohistochemistry staining for mismatch repair proteins: the endoscopic biopsy material provides useful and coherent results.

Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) in patients with colorectal cancer can be performed on endoscopic biopsy material or the surgical resection material. Data are continuing to accumulate regarding the deleterious effect of neoadjuvant chemoradiation on MMRP expression. However, despite continuing rise in the use of endoscopic biopsies for IHC, most pathology departments still use mainly the surgical materials for IHC testing. In this study we compared the quality of stains among 96 colon cancer subjects with paired endoscopic and surgical material available for MLH1, MSH2, MSH6, and PMS2 stains (96 × 4, yielding 384 paired stains). Each slide received both a quantitative score (immunoreactivity [0-3] × percent positivity [0-4]) and a qualitative score (absent; weak and focal; strong). The quantitative scores of all MMRP were significantly higher among the endoscopic material (P<.001 for all). In 358 pairs (93.2%), both the endoscopic and operative material stained either strong (322, 83.9%) or absent (36, 9.4%). In 26 pairs (6.8%), the endoscopic material stained strong, whereas the operative material stained focal and weak. No endoscopic biopsy materials stained focal and weak. Our findings indicate that the biopsy material may provide more coherent results. Although these results may indicate that biopsy material provides coherent and useful results, it is yet to be determined if the demonstrated differences pose a real clinical problem in interpreting final results of IHC staining of such kind. Hence, we suggest that when available, the endoscopic material rather than the operative one should serve as the primary substrate for IHC staining.

Efficacy and safety of chloramphenicol: joining the revival of old antibiotics? Systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Chloramphenicol is an old broad-spectrum antibiotic. We assessed its efficacy and safety. METHODS: This was a systematic review and meta-analysis. Electronic databases were searched to identify randomized controlled trials (RCTs) that assessed patients, of any age, with systemic bacterial infections that can cause sepsis and compared chloramphenicol alone versus other antibiotics. No restrictions on the date of publication, language or publication status were applied. The primary outcome assessed was overall mortality. RESULTS: Sixty-six RCTs fulfilled the inclusion criteria, and these included 9711 patients. We found a higher mortality with chloramphenicol for respiratory tract infections [risk ratio (RR) 1.40, 95% CI 1.00-1.97] and meningitis (RR 1.27, 95% CI 1.00-1.60), both without heterogeneity. The point estimate was similar for enteric fever, without statistical significance. No statistically significant difference was found between chloramphenicol and other antibiotics regarding treatment failure, except for enteric fever (RR 1.46, 95% CI 1.07-2.00, without heterogeneity). This difference derived mainly from studies comparing chloramphenicol with fluoroquinolones (RR 1.85, 95% CI 1.07-3.2). There were no statistically significant differences between chloramphenicol and other antibiotics in terms of adverse events, including haematological events, except for anaemia, which occurred more frequently with chloramphenicol (RR 2.80, 95% CI 1.65-4.75, I(2) =0%), and gastrointestinal side effects, which were less frequent with chloramphenicol (RR 0.67, 95% CI 0.46-0.99, I(2) =0%). Many of the studies included were sponsored by pharmaceutical companies marketing the comparator drug to chloramphenicol, and this might have influenced the results. CONCLUSIONS: Chloramphenicol cannot be recommended as a first-line treatment for respiratory tract infections, meningitis or enteric fever as alternatives are probably more effective. Chloramphenicol is as safe as treatment alternatives for short antibiotic courses. RCTs are needed to test this treatment against MDR organisms when better alternatives do not exist.