Cardiovascular risk profiles and 20-year mortality in older people: gender differences in the Pro.V.A. study.

The age- and gender-related cardio-metabolic changes may limit the applicability of guidelines for the prevention of cardiovascular diseases (CVD) in older people. We investigated the association of cardiovascular risk profile with 20-year all-cause and CVD-mortality in older adults, focusing on age- and gender-specific differences. This prospective study involved 2895 community-dwelling individuals aged ≥65 years who participated in the Pro.V.A study. The sum of achieved target levels (smoking, diet, physical activity, body weight, blood pressure, lipids, and diabetes) recommended by the European Society of Cardiology 2016 guidelines was assessed in each participant. From this sum, cardiovascular risk profile was categorised as very high (0-2), high (3), medium (4), low (5), and very low (6-7 target levels achieved). All-cause and CV mortality data over 20 years were obtained from health registers. At Cox regression, lower cardiovascular risk profile was associated with reduced 20-year all-cause mortality in both genders, with stronger results for women (HR = 0.42 [95%CI:0.25-0.69] and HR = 0.61 [95%CI:0.42-0.89] for very low vs. very high cardiovascular risk profile in women and men, respectively). This trend was more marked for CVD mortality. Lower cardiovascular risk profile was associated with reduced all-cause and CVD mortality only in men < 75 years, while the associations persisted in the oldest old women. A lower cardiovascular risk profile, as defined by current guidelines, may reduce all-cause and CVD mortality in older people, with stronger and longer benefits in women. These findings suggest that personalised and life-course approaches considering gender and age differences may improve the delivery of preventive actions in older people. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10433-021-00620-y.

Association of body surface area with fat mass, free fat mass and total weight in healthy individuals, and implications for the dosage of cytotoxic drugs.

BACKGROUND & AIMS: In oncology, the dosage of anti-neoplastic drugs is generally adapted to the patient's body surface area (BSA). We investigated the potential differences between BSA and body weight (BW) in estimating the variability in body composition among individuals, especially older adults. MATERIALS AND METHODS: The study population included 322 community-dwelling individuals with different age and sex: 45 adult men (AM, age 18-65 years), 86 older men (OM, age >65 years), 54 adult women (AW, age 18-65 years), and 137 older women (OW, age >65 years). For each participant, we estimated the body composition with dual-energy X-ray absorptiometry, and we calculated the BSA using the DuBois and DuBois formula. The strength of relationships between fat free mass (FFM) and fat mass (FM) with BSA, BW, and BMI were expressed as correlation (r) and determination coefficients (R2). RESULTS: Most of the included sample was normal weight (45.7%) or overweight (41.9%). FFM demonstrated a stronger association with BSA than with BW or BMI in all age/sex groups, with r ranging from 0.831 to 0.924 (p < 0.001 for all) and R2 from 0.691 to 0.853. Conversely, BW and BMI were more strongly related to FM than BSA, especially in women. For such relationship, BW, in particular, showed r ranging from 0.793 to 0.924 (p < 0.001 for all). CONCLUSIONS: This study suggests that BSA may be more appropriately used to estimate FFM, compared with BW. Instead, alternative parameters should be considered to estimate FM in patients at risk for adverse effects of lipophilic drugs, especially in older age.

Mild polypharmacy and MCI progression in older adults: the mediation effect of drug-drug interactions.

BACKGROUND: Polypharmacy has been associated with worse cognitive performance, but its impact on mild cognitive impairment (MCI) progression to dementia has not been explored. AIMS: The aims of the study were to investigate the association between multidrug regimens and MCI progression, and the possible mediation of drug-drug interactions and drugs' anticholinergic effect in such association. METHODS: This work included 342 older adults with MCI, who were involved in an Italian multicenter population-based cohort study. Information on drugs taken was derived from general practitioners' records and data on drug-drug interactions and anticholinergic burden [evaluated through the Anticholinergic Cognitive Burden and the Anticholinergic Risk Scale (ARS)] were extracted. Multinomial logistic regressions assessed the associations between mild polypharmacy (≥ 3 drugs/day), drug-drug interactions, and anticholinergic burden with MCI changes after 1-year follow-up. Mediation analysis evaluated potential mediators of that relationship. RESULTS: Approximately, 50% of participants took ≥ 3 drugs/day. During the follow-up, 4.1% of MCI patients progressed to dementia. The odds of developing dementia was sixfold higher in those who took ≥ 3drugs/day (OR = 6.04, 95% CI 1.19-30.74), eightfold higher in those with ≥ 1 drug-drug interaction/s (OR = 8.45, 95% CI 1.70-41.91), and fivefold higher in those with ARS ≥ 1 (OR = 5.10, 95% CI 1.04-24.93). Drug-drug interactions mediated 70.4% of the association between medication number and MCI progression to dementia (p = 0.07). DISCUSSION: Our study suggests that even mild polypharmacy may increase the risk of MCI progression to dementia, probably due to the presence of drug-drug interactions, which often occur in multidrug regimens. CONCLUSIONS: Older people require careful management of pharmacological treatments, with special attention to drug-drug interactions and drug-related anticholinergic effects.

The Impact of Smoking on Bone Metabolism, Bone Mineral Density and Vertebral Fractures in Postmenopausal Women.

BACKGROUND: Smoking is recognized among the risk factors for osteoporosis, but only few studies have comprehensively explored its influence on bone metabolism and strength. We aimed to evaluate smoking effects on calcium-phosphate metabolism, bone mineral density (BMD) and fracture risk in postmenopausal women. METHODS: Our sample included 1067 postmenopausal women who arrived to our osteoporosis outpatient clinic. Anamnestic data, smoking habits (categorized as never, former, and current; and by smoking intensity and duration), biochemical parameters, lumbar/femoral BMD, and presence of vertebral fractures were recorded. In a subsample of 357 women, the changes in BMD after a 2-yr follow-up period were also assessed. RESULTS: Current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers. They also had lower PTH values and weaker linear association between serum vitamin D and parathyroid hormone (current ß = -0.11[SE = 0.004]; former ß = -0.14[SE = 0.01]; never ß = -0.20[SE = 0.003]; p < 0.01 for all). Baseline BMD did not reflect differences based on smoking habits, duration or intensity. However, after 2 years, only current smokers significantly worsened in femural BMD. After adjustment for confounders, the chance of having sustained vertebral fractures at the first evaluation increased by 74% (95% confidence interval:1.07-2.83) in current compared with never smokers, especially among heavy smokers. CONCLUSIONS: Smoking may negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur. No significant differences were observed in these outcomes among former smokers, suggesting that quitting smoking has beneficial effects on bone health.

Decision tree for ward admissions of older patients at the emergency department after a fall.

AIM: Falls are a prevalent issue for the older population, and for the healthcare system in terms of emergency department (ED) access and hospitalizations. There is still a lack of knowledge and guidelines, however, regarding the need to hospitalize older patients accessing the ED after a fall. In the present study, we aimed to analyze the factors and the decisional process that led to older patients accessing the ED after a fall being admitted to hospital or discharged. METHODS: The study sample included 2144 older people who accessed the ED after a fall. For each patient, we obtained information on the nature of the fall and the related injuries, previous falls, dementia and ongoing medical therapies. As the outcome variable, we considered the indication for ward admission after the ED visit. RESULTS: Of the 2144 individuals who accessed the ED after a fall, 38% had at least one fracture, and 40.1% were admitted to a ward. The decision tree obtained using the chi-squared automatic interaction detection algorithm showed that the indication for ward admission could be accurately predicted (risk estimate 0.205) by just five factors, namely: presence and severity of fall-related injuries, reportedly suspicious fall dynamics, use of anticoagulants, polypharmacy, and dementia. CONCLUSIONS: The need for ward admission in older patients who access the ED after a fall seems to be determined not only by the severity of fall-related injuries, but also by the fall dynamics and the individual's clinical complexity. Geriatr Gerontol Int 2018; 18: 1388-1392.

Monoclonal gammopathy of undetermined significance and bone health outcomes: a systematic review and exploratory meta-analysis.

Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in the elderly. A number of studies have investigated the relationship between MGUS and bone health outcomes including bone mineral density (BMD), osteoporosis and fractures, but no meta-analysis exists. We conducted a systematic review and exploratory meta-analysis comparing bone health outcomes in patients with MGUS. Two independent authors searched PubMed and Scopus from inception until 19 October 2016. A meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD was conducted. Standardised mean differences (SMD) ± 95% confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures. Of 174 initial hits, 10 studies of moderate methodological quality were eligible, including 8711 individuals with MGUS vs. 52,865 controls. Compared to controls, subjects with MGUS showed significantly lower values for radial cortical volumetric BMD (1 study; SMD = -5.45, 95% CI: -7.24 to -3.66), but not at the lumbar spine, femoral neck or hip. The incidence of fractures was higher in people with MGUS (n = 7466) vs. controls (n = 52,304) (RR = 1.36, 95% CI 1.28-1.44, I 2 = 0%) over a median of 12.5-year follow-up. The incidence of vertebral fractures was particularly elevated (RR = 2.50, 95% CI 1.53-4.06) although limited to two studies. In conclusion, although with limitations, our preliminary meta-analysis suggests that patients with MGUS are at higher risk of fractures despite evidence for differences in BMD being equivocal. Future longitudinal research is required to confirm our findings and determine if fracture prevention interventions are warranted in people with MGUS.

Factors influencing short-term outcomes for older patients accessing emergency departments after a fall: The role of fall dynamics.

BACKGROUND: While the relevance of falls in raising the risk of fractures, hospitalization and disability in older age is well recognized, the factors influencing the onset of fractures and the need for ward admission after a fall have yet to be fully elucidated. We investigated which factors and fall dynamics were mainly associated with fall-related injuries and hospitalization among elderly persons accessing the Emergency Department (ED) following a fall. METHODS: The study involved 2144 older subjects who accessed the ED after a fall. Data on the fall´s nature and related injuries, ward admissions, history of falls, dementia, and medical therapies were examined for all patients. Considering dynamics, we distinguished accidental falls (due to interaction with environmental hazards while in motion) and falls from standing (secondary to syncope, lipothymia, drop attack, or vertigo). RESULTS: The overall prevalence of fractures in our population did not differ significantly with advancing age, though hip fractures were more common in the oldest, and upper limb fractures in the youngest patients. Falls from standing were associated with polypharmacy and with higher ward admission rate despite a lower fractures´ prevalence than accidental falls. The chances of fall-related fractures were more than fourfold as high for accidental dynamics (OR=4.05, 95%CI:3.10-5.29, p<0.0001). Ward admission was associated with polypharmacy, dementia, anticoagulants´ use and fall-related fractures (OR=6.84, 95%CI:5.45-8.58, p<0.0001), while it correlated inversely with accidental fall dynamics. CONCLUSIONS: Outcomes of falls in older age depend not only on any fall-related injuries, but also on factors such as polypharmacy, cognitive status and fall dynamics.

Inflammation and sarcopenia: A systematic review and meta-analysis.

Inflammatory cytokines have been shown to prompt muscle wasting, ultimately stimulating protein catabolism and suppressing muscle synthesis. However, the possible association between inflammatory parameters and sarcopenia is poorly understood. We therefore aimed to summarize the current evidence about this topic with a meta-analysis of studies reporting serum inflammatory parameters in patients with sarcopenia vs. people without sarcopenia (controls). An electronic PubMed and Scopus search through to 09/01/2016 and meta-analysis of cross-sectional studies comparing serum levels of inflammatory cytokines between patients with sarcopenia and controls was made, calculating random-effects standardized mean differences (SMDs) ±95% confidence intervals (CIs) as the effect size. Out of 1370 initial hits, 17 studies with a total of 11249 participants (3072 with sarcopenia and 8177 without) were meta-analyzed. Sarcopenic participants had significantly higher levels of CRP (SMD=0.51; 95%CI 0.26, 0.77; p<0.0001; I2=96%) than controls. Conversely, serum IL6 levels were not significantly different (SMD=0.35; 95%CI: -0.19, 0.89; p=0.21; I2=97%) in people with sarcopenia versus controls. Sarcopenic people did not have higher levels of TNF-α than controls (SMD=0.28; 95%CI -0.26, 0.83; p=0.31; I2=97%). In conclusion, sarcopenia seems to be associated with elevated serum CRP levels; future longitudinal studies are needed to clarify this relationship.

Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis.

Whilst obesity is associated with a higher risk of cognitive impairment, the influence of weight loss on cognitive function in obese/overweight people is equivocal. We conducted a meta-analysis of randomized controlled trials (RCTs) and longitudinal studies evaluating the influence of voluntary weight loss on cognitive function in obese/overweight individuals. Articles were acquired from a systematic search of major databases from inception till 01/2016. A random effect meta-analysis of weight loss interventions (diet, physical activity, bariatric surgery) on different cognitive domains (memory, attention, executive functions, language and motor speed) was conducted. Twenty studies (13 longitudinal studies=551 participants; 7 RCTs=328 treated vs. 140 controls) were included. Weight loss was associated with a significant improvement in attention and memory in both longitudinal studies and RCTs, whereas executive function and language improved in longitudinal and RCT studies, respectively. In conclusion, intentional weight loss in obese/overweight people is associated with improvements in performance across various cognitive domains. Future adequately powered RCTs are required to confirm/refute these findings.

Factors Influencing Transitions Between Frailty States in Elderly Adults: The Progetto Veneto Anziani Longitudinal Study.

OBJECTIVES: To investigate frailty state transitions in a cohort of older Italian adults to identify factors exacerbating or improving frailty conditions. DESIGN: Population-based longitudinal study with mean follow-up of 4.4 years. SETTING: Community. PARTICIPANTS: Individuals enrolled in the Progetto Veneto Anziani (Pro.V.A.) (N = 2,925; n = 1,179 male, n = 1,746 female; mean age 74.4 ± 7.3). MEASUREMENTS: Frailty was identified at baseline and follow-up based on the presence of at least three Fried criteria; prefrailty was defined as the presence of one or two Fried criteria. Anthropometric, socioeconomic, and clinical characteristics were assessed at baseline in a personal interview and clinical examination using validated scales and medical history. RESULTS: During the study period, 1,114 (38.1%) subjects retained their baseline frailty status, 1,066 (36.4%) had a transition in frailty status, and the remainder of the sample died. Older age, female sex, obesity, cardiovascular disease, osteoarthritis, smoking, loss of vision, low levels of self-sufficiency and physical performance, cognitive impairment, hypovitaminosis D, hyperuricemia, and polypharmacy were associated with increasing frailty and greater mortality. Conversely, overweight, low to moderate drinking, high educational level, and living alone were associated with decreasing frailty. CONCLUSIONS: Frailty was confirmed as a dynamic syndrome, with socioeconomic and clinical factors that could be targets of preventive actions influencing transitions to better or worse frailty status.

Taste loss in the elderly: Possible implications for dietary habits.

Aging may coincide with a declining gustatory function that can affect dietary intake and ultimately have negative health consequences. Taste loss is caused by physiological changes and worsened by events often associated with aging, such as polypharmacy and chronic disease. The most pronounced increase in elderly people's detection threshold has been observed for sour and bitter tastes, but their perception of salty, sweet, and umami tastes also seems to decline with age. It has often been suggested that elderly people who lose their sense of taste may eat less food or choose stronger flavors, but the literature has revealed a more complicated picture: taste loss does not appear to make elderly people prefer stronger flavors, but nutrition surveys have pointed to a greater consumption of sweet and salty foods. Real-life eating habits thus seem to be more influenced by other, social and psychological factors. Elderly gustatory function is worth investigating to identify dietary strategies that can prevent the consequences of unhealthy eating habits in the elderly. This paper discusses age-related changes in taste perception, focusing on their consequences on food preferences, and pointing to some strategies for preserving appropriate dietary habits in elderly people.

Sinonasal polyposis in the elderly.

BACKGROUND/OBJECTIVE: The main end point of this investigation was to review our experience gained from 2009 to 2015 of treating chronic rhinosinusitis with nasal polyps (CRSwNP) in elderly patients (≥65 years old) with functional endoscopic sinus surgery. Secondary aims were to analyze the prognostic variables for CRSwNP in elderly patients and to compare the demographic, clinical, laboratory, histologic, and prognostic characteristics of CRSwNP in elderly versus young adult patients (20-40 years old). METHODS: Forty-three consecutive elderly patients and 71 consecutive young adult patients with CRSwNP were enrolled. RESULTS: Significant associations were found in the elderly group between CRSwNP recurrence and allergy (p = 0.037), CRSwNP recurrence and asthma (p = 0.017), and CRSwNP recurrence and acetyl salicylic acid (ASA) intolerance (p = 0.032) but not between recurrence and eosinophilic/noneosinophilic CRSwNP histology. Significant associations emerged in the young adult group between CRSwNP recurrence and asthma (p = 0.009), and ASA intolerance (p = 0.016), and serum eosinophil count (p = 0.02). The recurrence rate was also significantly higher for young adult patients with eosinophilic-type CRSwNP (p = 0.001). CRSwNP recurred less often in the elderly than in the young adult patients (p = 0.05). CONCLUSION: The present preliminary investigation found a lower recurrence rate after functional endoscopic sinus surgery for CRSwNP in elderly patients than in young adult patients. Further investigations on larger, prospective series are mandatory to support the hypothesis that, although eosinophilic-type CRSwNP is generally considered a variant at high risk of recurrence and that probably warrants stricter postoperative follow-up and adjuvant postoperative medical treatment, these considerations could not be applied to elderly patients.

Extranodal extension of lymph node metastasis is a marker of poor prognosis in oesophageal cancer: a systematic review with meta-analysis.

The extranodal extension (ENE) of nodal metastasis is the extension of neoplastic cells through the nodal capsule into the perinodal adipose tissue. This histological feature has recently been indicated as an important prognostic factor in different types of malignancies; in this manuscript, we aim at defining its role in the prognosis of oesophageal cancer with the tool of meta-analysis. Two independent authors searched SCOPUS and PubMed until 31 August 2015 without language restrictions. The studies with available data about prognostic parameters in subjects with oesophageal cancer, comparing patients with the presence of ENE (ENE+) versus only intranodal extension (ENE-), were considered as eligible. Data were summarised using risk ratios (RRs) for number of deaths/recurrences and HRs together with 95% CIs for time-dependent risk related to ENE+, adjusted for potential confounders. Fourteen studies were selected; they followed-up 1437 patients with oesophageal cancer for a median follow-up of 39.4 months. The presence of ENE was associated with a significantly increased risk of all-cause mortality (RR=1.33; 95% CI 1.18 to 1.50, p<0.0001, I2=49%; HR=2.72, 95% CI 2.03 to 3.64, p<0.0001, I2=0%), cancer-specific mortality (RR=1.35; 95% CI 1.14 to 1.59, p=0.001, I2=57%; HR=1.97, 95% CI 1.41 to 2.75, p<0.0001, I2=41%) and of risk of recurrence (RR=1.50, 95% CI 1.20 to 1.88, p<0.0001, I2=9%; HR=2.27, 95% CI 1.72 to 2.90, p<0.0001, I2=0%). On the basis of these results, in oesophageal cancer, ENE should be considered from the gross sampling to the pathology report, and in future oncological staging system.

Extranodal Extension of Nodal Metastases Is a Poor Prognostic Indicator in Gastric Cancer: a Systematic Review and Meta-analysis.

INTRODUCTION: The extranodal extension (ENE) of nodal metastases (the extension of neoplastic cells through the nodal capsule into the perinodal soft tissue) is a histological feature that has been considered a prognostic factor in several cancers, but the role in gastric cancer was not yet investigated. We aimed to investigate the prognostic role of ENE in patients affected by gastric cancer through a systematic review and meta-analysis. MATERIAL AND METHODS: Two independent authors searched major databases until 09/30/2015 to identify studies providing data on gastric cancer patients' prognostic parameters and comparing patients with ENE (ENE+) vs intra-nodal extension (ENE-). The data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for potential confounders. RESULTS: Nine studies followed up 3250 patients with gastric cancer (1064 ENE+ and 2186 ENE-). ENE+ was associated with a significantly higher risk of all-cause mortality (RR = 1.70; 95 % CI: 1.43-2.03, I (2) = 66 %; HR = 2.14; 95 % CI: 1.66-2.75, I (2) = 0 %), cancer-specific mortality (RR = 1.59; 95 % CI: 1.42-1.79; HR = 1.52; 95 % CI: 1.19-1.96), and disease recurrence (RR = 3.43, 95 % CI: 1.80-6.54, I (2) = 0 %). DISCUSSION: Judging from our results, ENE in gastric cancer patients should be considered for prognostic purposes from the gross sample to the pathology report.

Prognostic implications of extranodal extension in node-positive squamous cell carcinoma of the vulva: A systematic review and meta-analysis.

Squamous cell carcinoma (SCC) of the vulva is the fourth most common gynecological cancer, usually staged with the TNM or FIGO systems. Since 2009, FIGO staging has taken the extranodal extension (ENE) of lymph node metastases into account. ENE is defined as the spread of a lymph node metastasis into surrounding soft tissue. Although the TNM and FIGO systems acknowledge the importance of ENE in SCC, no comprehensive studies have analyzed the prognostic impact of this parameter. We therefore queried the PubMed and SCOPUS databases from their inception up until 04/01/2015, adopting no language restrictions: all prospective studies reporting on prognostic parameters in patients with vulvar SCC, and comparing participants with and without ENE were eligible for our analysis. Data were summarized using risk ratios (RR) for the number of deaths/recurrences and hazard ratios (HR) for the time-dependent risk related to ENE positivity, adjusting for potential confounders. Among 859 hits, 13 studies were found eligible and were included in our meta-analysis. Compared with ENE-negative (ENE-) cases, the ENE-positive (ENE+) patients had significantly higher rates of all-cause mortality (6 studies: RR = 3.18; 95%CI: 2.02-5.00, p < 0.0001, I(2) = 56%), cancer-specific mortality (3 studies: RR = 2.03; 95%CI: 1.12-3.69, p = 0.02, I(2) = 80%), and recurrence (4 studies: RR = 2.69, 95%CI: 1.61-3.76, p < 0.0001, I(2) = 57%). Using HRs after adjusting for potential confounders, ENE + carried a significantly higher risk of all-cause mortality (6 studies: HR = 3.08, 95%CI: 1.73-5.48, p < 0.0001, I(2) = 66%), and recurrence (5 studies: HR = 3.93, 95%CI: 2.33-6.62, p < 0.0001, I(2) = 28%). Our meta-analysis clarifies the prognostic significance of ENE in vulvar SCC, also pointing to its implications for gross sampling, histology and oncological staging.

Extranodal extension in N1-adenocarcinoma of the pancreas and papilla of Vater: a systematic review and meta-analysis of its prognostic significance.

The aim of the study was to investigate the prognostic role of extranodal extension (ENE) of lymph node metastasis in adenocarcinoma of the pancreas (PDAC) and papilla [cancer of the papilla of Vater (CPV)]. A PubMed and SCOPUS search from database inception until 5 January 2015 without language restrictions was conducted. Eligible were prospective studies reporting data on prognostic parameters in individuals with PDAC and/or CPV, comparing participants with the presence of ENE (ENE+) with those with intranodal extension (ENE-). Data were summarized using risk ratios for number of deaths/recurrences and hazard ratios for time-dependent risk related to ENE+, adjusted for potential confounders. ENE was found to be very common in these tumors (up to about 60% in both N1-PDAC and CPV), leading to a significant increased risk for all-cause mortality [risk ratio=1.20; 95% confidence interval (CI): 1.06-1.35, P=0.003, I(2)=44%; hazard ratio=1.415, 95% CI: 1.215-1.650, P<0.0001, I(2)=0%] and recurrence of disease (risk ratio=1.20, 95% CI: 1.03-1.40, P=0.02, I(2)=0%). On the basis of our results, in PDAC and CPV, ENE should be considered mandatorily from the gross sampling and pathology report to the oncologic staging and therapeutic approach.

Short article: Relapsing Whipple's disease: a case report and literature review.

Whipple's disease is a rare infection caused by Tropheryma whipplei, a Gram-negative Bacillus usually found in macrophages of the lamina propria of the small intestine. The typical clinical manifestations of classic Whipple's disease are diarrhea, weight loss, malabsorption, abdominal pain, and arthralgia. The disease's laboratory diagnosis is currently based on duodenal biopsy. Treatment generally includes primary therapy for 2 weeks with intravenous antibiotics capable of reaching high levels in the cerebrospinal fluid, such as ceftriaxone, usually followed by treatment with oral cotrimoxazole for 1 year. Early diagnosis should enable appropriate treatment and improves the prognosis, and prolonged antibiotic treatment often leads to complete remission. Our case report focuses on a 72-year-old man who had been passing watery stools for 1-2 months, accompanied by low-grade fever. He reported profound asthenia, a weight loss of about 3 kg, and loss of appetite. Thirty years earlier (in 1984), he had been working as a horse keeper at a University Department of Agricultural and Veterinary Studies, where he had contracted Whipple's disease. Laboratory tests and microbiological studies led to a diagnosis of recurrent Whipple's disease. Esophagogastroduodenoscopy was performed under deep sedation. Biopsy samples obtained from the stomach and duodenum were stained with hematoxylin and eosin, Giemsa, and periodic acid-Schiff to identify any accumulation of typical periodic acid-Schiff-positive macrophages in the lamina propria. A specific quantitative real-time PCR assay using specific oligonucleotide probes for targeting repeated sequences of Tropheryma whipplei was also performed to detect its DNA in the duodenum samples.

Oxidative Stress and Antioxidant Levels in Patients with Anorexia Nervosa after Oral Re-alimentation: A Systematic Review and Exploratory Meta-analysis.

Oxidative stress markers seem to be higher in patients with anorexia nervosa (AN) than healthy controls, but the potentially beneficial effects of weight gain is not known. We calculated random effects standardised mean differences (SMDs) as effect size measures of oxidative stress marker changes after re-alimentation reported in two or more studies, summarising others descriptively. Seven longitudinal studies (n = 104) were included. After a median follow-up period of 8 weeks, AN patients significantly increased their body mass index (15.1 ± 2.1 to 17.1 ± 2.2, p < 0.0001). This weight gain was followed by a significant increase in serum levels of the antioxidant albumin (studies = 6, SMD = 0.50, 95%CI = 0.18; 0.82, p = 0.002; I(2) = 16%) and a significant decrease in the oxidative stress marker Apolipoprotein B (studies = 2, n = 19, SMD = -0.85, 95%CI = -1.53; -0.17, p = 0.01; I(2) = 0). In one study, catalase and total antioxidant capacity increased, whilst superoxide dismutase significantly decreased. In conclusion, oral re-alimentation, even without full-weight normalisation, seems to improve oxidative stress in people with AN.

Prognostic impact of extra-nodal extension in thyroid cancer: A meta-analysis.

BACKGROUND AND OBJECTIVES: Lymph node involvement is common in thyroid cancer, but the system of staging does not consider the histological features of lymph node metastases. We conducted a meta-analysis to investigate the prognostic role of extranodal extension (ENE) in thyroid cancer patients. METHODS: We ran PubMed and SCOPUS searches without language restrictions. Prospective studies reporting data on overall mortality, cancer-specific mortality, or disease recurrence including thyroid cancer patients, in which cases with ENE (ENE+) were compared with those with only intranodal disease (ENE-) were eligible. Data were summarized using risk ratios (RR) for number of deaths/recurrences, and hazard ratios (HR) for time-dependent risks related to ENE+ status, adjusted for potential confounders. RESULTS: Of 414 hits, 23 studies were eligible and included. Compared to ENE-, patients who were ENE+ had significantly higher rates of all-cause mortality (studies = 8; RR = 3.25; 95%CI: 1.35-2.64, I(2) = 83%) and recurrence (studies = 17; RR = 2.64, 95%CI: 1.93-3.60, I(2) = 73%). Using HRs adjusted for potential confounders, ENE+ status carried a significantly higher risk of all-cause and cancer-specific mortality and disease recurrence. CONCLUSION: It becomes mandatory to consider ENE in the histopathological examination of surgical samples in thyroid cancer patients, and this factor should be included in future oncological staging systems.

Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis.

Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A-, assessed either via immunohistochemistry (loss of expression) or with genetic testing (presence of mutation). Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to ARID1A- adjusted for potential confounders. Of 136 hits, 25 studies with 5,651 participants (28 cohorts; ARID1A-: n = 1,701; ARID1A+: n = 3,950), with a mean follow-up period of 4.7 ± 1.8 years, were meta-analyzed. Compared to ARID1A+, ARID1A- significantly increased cancer-specific mortality (studies = 3; RR = 1.55, 95% confidence interval (CI) = 1.19-2.00, I(2) = 31%). Using HRs adjusted for potential confounders, ARID1A- was associated with a greater risk of cancer-specific mortality (studies = 2; HR = 2.55, 95%CI = 1.19-5.45, I(2) = 19%) and cancer recurrence (studies = 10; HR = 1.93, 95%CI = 1.22-3.05, I(2) = 76%). On the basis of these results, we have demonstrated that loss of ARID1A shortened time to cancer-specific mortality, and to recurrence of cancer when adjusting for potential confounders. For its role, this gene should be considered as an important potential target for personalized medicine in cancer treatment.