Is preoperative physical function testing predictive of length of stay in patients with colorectal cancer? A retrospective study.

Surgery is the primary treatment for colorectal cancer. A prolonged Length of Stay (pLOS) can increase risk of complications and physical inactivity, leading to a decline in physical function. While promising results were seen from preoperative exercise training and post-operative functional recovery, the predictive potential of preoperative physical function has not yet been investigated. The objective of this study is to determine if preoperative physical function can predict pLOS in patients with colorectal cancer. A total of 459 patients from 7 cohorts were analyzed. Logistic regression was used to determine risk of pLOS (>3 days), and ROC curve was plotted to establish sensitivity/specificity. Selected variables included age, sex, BMI, comorbidity, ASA status, tumor site, surgical approach, handgrip strength, Timed-Up and Go, 30-s Sit-to-Stand, 30-s Arm Curl Test, 6-Minute-Walking Test (6MWT), CHAMPS Physical Activity Questionnaire for Older Adult and the 36-Item Short Form Survey. The results showed that patients with rectal tumor are 2.7x more at risk to be in the pLOS group compared to those with colon tumor (O.R. 2.7; C.I. 1.3-5.7, p=0.01). For every increment of 20 m in 6MWT, there is a decreased risk of 9% of being in pLOS group (C.I. 1.03-1.17, p=0.00). A cut-off of 431 m can predict 70% of patients in pLOS group (AUC 0.71 C.I 0.63-0.78, p=0.00). Tumor site (rectal) and 6MWT were significant predictors of pLOS. Using the 6MWT as a screening tool for pLOS with cut-off of 431 m should be implemented in the preoperative surgical pathway.

Malnutrition modifies the response to multimodal prehabilitation: a pooled analysis of prehabilitation trials.

Patients with colorectal cancer are at risk of malnutrition before surgery. Multimodal prehabilitation (nutrition, exercise, stress reduction) readies patients physically and mentally for their operation. However, it is unclear whether extent of malnutrition influences prehabilitation outcomes. We conducted a pooled analysis from five 4-week multimodal prehabilitation trials in colorectal cancer surgery (prehabilitation: n = 195; control: n = 71). Each patient's nutritional status was evaluated at baseline using the Patient-Generated Subjective Global Assessment (PG-SGA; higher score, greater need for treatment of malnutrition). Functional walking capacity was measured with the 6-minute walk test distance (6MWD) at baseline and before surgery. A multivariable mixed effects logistic regression model evaluated the potential modifying effect of PG-SGA on a clinically meaningful change of ≥19 m in 6MWD before surgery. Multimodal prehabilitation increased the odds by 3.4 times that colorectal cancer patients improved their 6MWD before surgery as compared with control (95% confidence interval (CI): 1.6 to 7.3; P = 0.001, n = 220). Nutritional status significantly modified this outcome (P = 0.007): Neither those patients with PG-SGA ≥9 (adjusted odds ratio: 1.3; 95% CI: 0.23 to 7.2, P = 0.771, n = 39) nor PG-SGA <4 (adjusted odds ratio: 1.3; 95% CI: 0.5 to 3.8, P = 0.574, n = 87) improved in 6MWD with prehabilitation. In conclusion, baseline nutritional status modifies prehabilitation effectiveness before colorectal cancer surgery. Patients with a PG-SGA score 4-8 appear to benefit most (physically) from 4 weeks of multimodal prehabilitation. Novelty: Nutritional status is an effect modifier of prehabilitation physical function outcomes. Patients with a PG-SGA score 4-8 benefited physically from 4 weeks of multimodal prehabilitation.

Older frail prehabilitated patients who cannot attain a 400 m 6-min walking distance before colorectal surgery suffer more postoperative complications.

INTRODUCTION: Recent efforts to prehabilitate intermediately frail and frail (Fried frailty criteria ≥2) elective colorectal cancer patients did not influence clinical nor functional outcomes. The objective of this secondary analysis was to describe the subset of intermediately frail and frail prehabilitated patients who could not attain a minimum 400 m (a prognostic cut-point used in other patient populations) 6-min walking distance (6MWD) before elective surgery. MATERIALS AND METHODS: Secondary analysis of a randomized controlled trial. Patients participated in multimodal prehabilitation at home and in-hospital for approximately four weeks before colorectal surgery. Primary outcome was incidence of postoperative complications within 30 days of hospital discharge. RESULTS: Sixty percent of the patients who participated in prehabilitation did not reach a minimum walking distance of 400 m in 6 min before surgery. Compared to the group that attained ≥400 m 6MWD (n = 19), the <400 m group (n = 28) were older, had higher percent body fat, lower physical function, lower self-reported physical activity, higher American Society of Anesthesiologists (ASA) classification, and twice as many were in critical need of a nutrition intervention at baseline. No group differences were observed regarding frailty status (P = 0.775). Sixty-one percent of the <400 m 6MWD group experienced at least one complication within 30 days of surgery compared to 21% in the ≥400 m group (P = 0.009). CONCLUSION: Several preoperative characteristics were identified in the <400 m 6MWD group that could be useful in screening and targeting future prehabilitative treatments. Future trials should investigate use of a 400 m standard for the 6MWD as a minimal treatment target for prehabilitation.

Multi-modal prehabilitation: addressing the why, when, what, how, who and where next?

Just as there is growing interest in enhancing recovery after surgery, prehabilitation is becoming a recognised means of preparing the patient physically for their operation and/or subsequent treatment. Exercise training is an important stimulus for improving low cardiovascular fitness and preserving lean muscle mass, which are critical factors in how well the patient recovers from surgery. Despite the usual focus on exercise, it is important to recognise the contribution of nutritional optimisation and psychological wellbeing for both the adherence and the response to the physical training stimulus. This article reviews the importance of a multi-modal approach to prehabilitation in order to maximise its impact in the pre-surgical period, as well as critical future steps in its development and integration in the healthcare system.

Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018.

BACKGROUND: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol. METHODS: A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly. CONCLUSIONS: The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.

The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years.

BACKGROUND: Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. METHODS: This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. RESULTS: The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p <  0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%. CONCLUSIONS: MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.

The impact of complications after elective colorectal resection within an enhanced recovery pathway.

BACKGROUND: Despite the implementation of enhanced recovery pathways (ERP), morbidity following colorectal surgery remains high. The aim of the present study was to estimate the impact of postoperative complications on excess hospital length of stay (LOS) in patients undergoing elective colorectal resection. METHODS: A retrospective study of patients undergoing elective colorectal surgery at a single institution from 2003 to 2010 was performed. Patients managed by an ERP were compared to conventional care (CC), matched by propensity score radius matching. Complications were defined a priori. Excess (independent effect on LOS from multivariate analysis) and attributable (absolute number of additional bed days) LOS of common postoperative complications determined the impact of complications on bed utilization. Multivariate analysis was performed using multiple linear regression. RESULTS: A total of 810 propensity-score-matched patients were included (ERP = 472, CC = 338). Complications were significantly lower in the ERP group compared to the CC group (20 vs. 31%, p < 0.001). Median LOS decreased from 7 days in the CC group to 5 days in the ERP group [adjusted decrease in mean LOS of 2.8 days (95% CI 0.8, 4.8)]. Anastomotic leak, myocardial infarction and C. difficile infection had the highest excess LOS for both the ERP and CC groups. However, impaired gastrointestinal function had a higher impact on the absolute number of hospital bed days in the ERP group, as high as anastomotic leak (72.7 vs. 73.5 days respectively), while in the CC group the impact of gastrointestinal dysfunction was less of that of anastomotic leak (50.6 vs. 78.9 days respectively). CONCLUSIONS: In the setting of an ERP, postoperative complications have significant impact on total bed utilization. Impaired gastrointestinal function, given its high incidence, accounted for almost the same number of additional hospital bed days as anastomotic leak in the ERP group and is a target for quality improvement.

The effects of added whey protein to a pre-operative carbohydrate drink on glucose and insulin response.

BACKGROUND: Pre-operative complex carbohydrate (CHO) drinks are recommended to attenuate post-operative insulin resistance. However, many institutions use simple CHO drinks, which while convenient, may have less metabolic effects. Whey protein may enhance insulin release when added to complex CHO. The aim of this study was to compare the insulin response to simple CHO vs. simple CHO supplemented with whey protein. METHODS: Twelve healthy volunteers participated in this double-blinded, within subject, cross-over design study investigating insulin response to simple CHO drink vs. simple CHO + whey (CHO + W) drink. The primary outcome was the accumulated insulin response during 180 min after ingestion of the drinks (Area under the curve, AUC). Secondary outcomes included plasma glucose and ghrelin levels, and gastric emptying rate estimated by acetaminophen absorption technique. Data presented as mean (SD). RESULTS: There was no differences in accumulated insulin response after the CHO or CHO + W drinks [AUC: 15 (8) vs. 20 (14) nmol/l, P = 0.27]. Insulin and glucose levels peaked between 30 and 60 min and reached 215 (95) pmol/l and 7 (1) mmol/l after the CHO drink and to 264 (232) pmol/l and 6.5 (1) mmol/l after the CHO + W drink. There were no differences in glucose or ghrelin levels or gastric emptying with the addition of whey. CONCLUSION: The addition of whey protein to a simple CHO drink did not change the insulin response in healthy individuals. The peak insulin responses to simple CHO with or without whey protein were lower than that previously reported with complex CHO drinks. The impact of simple carbohydrate drinks with lower insulin response on peri-operative insulin sensitivity requires further study.

Systematic review of exercise training in colorectal cancer patients during treatment.

Colorectal cancer surgery results in considerable postoperative morbidity, mortality and reduced quality of life. As many patients will undergo additional (neo)adjuvant therapy, it is imperative that each individual optimize their physical function. To elucidate the potential of exercise in patient optimization, we investigated the evidence for an exercise program before and after surgical treatment in colorectal cancer patients. A systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions, the guidelines of the Physical Therapy Journal and the PRISMA guidelines. No literature pertaining to exercise training during preoperative neoadjuvant treatment was found. Seven studies, investigating the effects of regular exercise during adjuvant chemotherapy for patients with colorectal cancer or a mixed population, were identified. A small effect (effect size (ES) 0.4) of endurance/interval training and strength training (ES 0.4) was found in two studies conducted in patients with colorectal and gastrointestinal cancer. In five studies that included a mixed population of cancer patients, interval training resulted in a large improvement (ES 1.5; P≤.05). Endurance training alone was found to increase both lower extremity strength and endurance capacity. The effects of strength training in the lower extremity are moderate, whereas, in the upper extremity, the increase is small. There is limited evidence available on exercise training during treatment in colorectal cancer patients. One study concluded exercise therapy may be beneficial for colorectal cancer patients during adjuvant treatment. The possible advantages of training during neoadjuvant treatment may be explored by prehabilitation trials.

Rendimento industrial, eficiência de fabricação e características físico-químicas de queijo colonial produzido de leite com dois níveis de células somáticas / Industrial yield, manufacturing efficiency and physical and chemical characteristics of colonial cheese produced from milk with two levels of somatic cells

Com base em dois níveis de contagem de células somáticas (CCS) do leite utilizado como matéria-prima, determinou-se influência no rendimento e na eficiência de fabricação do queijo colonial, em escala industrial. Os dois níveis de CCS foram formados do leite captado pela indústria, baixa CCS (<500.000 células/mL) e alta CCS (≥500.000 células/mL), sendo produzidos sete lotes de queijo para cada nível. O rendimento foi avaliado com rendimento simples (litros de leite/kg de queijo produzido) e rendimento seco (litros de leite/kg de sólidos totais de queijo produzido). A eficiência de fabricação do queijo foi avaliada por meio das perdas de sólidos no soro de queijo. Mediante análises multivariadas, demonstrou-se a relação entre altas CCS e a diminuição no rendimento simples e seco de queijo colonial, que apresentou também menor eficiência de fabricação, sem alterar a composição do queijo. Além disso, determinaram-se dados relativos às características físico-químicas de queijo colonial, o qual ainda não possui um regulamento técnico de identidade e qualidade. Conclui-se que a qualidade do leite tem influência direta na produção dos queijos e que, ao utilizar matéria-prima com alta CCS, a indústria assume os prejuízos do menor rendimento e da menor eficiência de fabricação dos queijos coloniais.(AU)

From two somatic cells count levels (SCC) of the milk used as raw material, the influence on the yield and cheese-making efficiency of colonial cheese was determined on an industrial scale. Both SCC levels were formed from milk received by the industry, being low SCC (<500.000 cells/mL) and high SCC (≥500.000 cells/mL), and seven batches of cheese were produced for each level. The yield was evaluated as simple yield (liters of milk/kg of cheese produced) and dry yield (liters of milk/kg of total solids of cheese produced). The cheese-making efficiency was evaluated by the loss of solids in cheese whey. Multivariate analysis showed a relationship between high SCC and decrease in simple and dry colonial cheese yield, which also had lower manufacturing efficiency, without altering the composition of the cheese. Moreover, data on the physical and chemical characteristics of colonial cheese were determined, that does not have Technical Regulation of Identity and Quality. We conclude that the quality of milk has a direct influence on the production of cheeses and, when using raw materials with high SCC, the industry takes the costs of worsening in performance and manufacturing efficiency in colonial cheese.(AU)

Suppression of interictal spikes during phasic rapid eye movement sleep: a quantitative stereo-electroencephalography study.

Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.

An updated Italian normative dataset for the Stroop color word test (SCWT).

The Stroop color and word test (SCWT) is widely used to evaluate attention, information processing speed, selective attention, and cognitive flexibility. Normative values for the Italian population are available only for selected age groups, or for the short version of the test. The aim of this study was to provide updated normal values for the full version, balancing groups across gender, age decades, and education. Two kinds of indexes were derived from the performance of 192 normal subjects, divided by decade (from 20 to 90) and level of education (4 levels: 3-5; 6-8; 9-13; >13 years). They were (i) the correct answers achieved for each table in the first 30 s (word items, WI; color items, CI; color word items, CWI) and (ii) the total time required for reading the three tables (word time, WT; color time, CT; color word time, CWT). For each index, the regression model was evaluated using age, education, and gender as independent variables. The normative data were then computed following the equivalent scores method. In the regression model, age and education significantly influenced the performance in each of the 6 indexes, whereas gender had no significant effect. This study confirms the effect of age and education on the main indexes of the Stroop test and provides updated normative data for an Italian healthy population, well balanced across age, education, and gender. It will be useful to Italian researchers studying attentional functions in health and disease.

Serum total estradiol, but not testosterone is associated with reduced bone mineral density (BMD) in HIV-infected men: a cross-sectional, observational study.

SUMMARY: By investigating the relationship between serum testosterone, estradiol, and bone mineral density (BMD) in a large cohort of HIV-infected men, estradiol was associated with BMD, relative estrogen deficiency being involved in bone loss in men with hypogonadism, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. INTRODUCTION: The purpose of this study is to evaluate the relationship between serum testosterone, estradiol, and BMD in a large cohort of HIV-infected men. METHODS: We investigated biochemical, hormonal parameters, and BMD in 1204 HIV-infected men (age 45.64 ± 7.33 years) participating in a cross-sectional, observational study. Among other parameters, the main outcome measures were serum total testosterone and estradiol, gonadotropins, 25-hydroxyvitamin D [25(OH)D], parathormone (PTH), calcium, phosphorous, femoral, and lumbar BMD. RESULTS: In men with HIV, the prevalence of osteoporosis and osteopenia is 15.1 and 63.2% with 25(OH)D insufficiency being very common (60.1%). After age adjustment, BMD is positively associated with estradiol, but not testosterone, at linear (p < 0.001) and stepwise (p < 0.05) multiple regression. Lumbar BMD significantly increases across the estradiol quartiles but not among testosterone quartiles. Femoral and lumbar BMD are significantly higher in men with estradiol ≥ 27 pg/mL than in those with estradiol <27 pg/mL. Apart from estradiol, only age, calcium, and BMI predict BMD at stepwise linear multiple regression, but the strength of this association is weak. CONCLUSIONS: Estradiol, but not testosterone, is associated with BMD in HIV-infected men and exerts a protective role on bone especially when it is above 27 pg/mL. Relative estrogen deficiency is a potential mechanism involved in bone loss in hypogonadal HIV-infected men, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. Finally, reduced BMD in young-to-middle-aged HIV-infected men might be considered a peculiar hallmark of HIV infection due to its relevant prevalence, representing one of the several pieces composing the complicated puzzle of premature aging related to HIV infection.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice.

BACKGROUND: The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme. METHODS: Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English-language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature. RESULTS: This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations. CONCLUSIONS: Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS®) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi-institutional prospective and adequately powered randomized trials.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 1: pathophysiological considerations.

BACKGROUND: The present article has been written to convey concepts of anaesthetic care within the context of an Enhanced Recovery After Surgery (ERAS) programme, thus aligning the practice of anaesthesia with the care delivered by the surgical team before, during and after surgery. METHODS: The physiological principles supporting the implementation of the ERAS programmes in patients undergoing major abdominal procedures are reviewed using an updated literature search and discussed by a multidisciplinary group composed of anaesthesiologists and surgeons with the aim to improve perioperative care. RESULTS: The pathophysiology of some key perioperative elements disturbing the homoeostatic mechanisms such as insulin resistance, ileus and pain is here discussed. CONCLUSIONS: Evidence-based strategies aimed at controlling the disruption of homoeostasis need to be evaluated in the context of ERAS programmes. Anaesthesiologists could, therefore, play a crucial role in facilitating the recovery process.

A normative study of the Italian printed word version of the free and cued selective reminding test.

According to the new research criteria for the diagnosis of Alzheimer's disease, episodic memory impairment, not significantly improved by cueing, is the core neuropsychological marker, even at a pre-dementia stage. The FCSRT assesses verbal learning and memory using semantic cues and is widely used in Europe. Standardization values for the Italian population are available for the colored picture version, but not for the 16-item printed word version. In this study, we present age- and education-adjusted normative data for FCSRT-16 obtained using linear regression techniques and generalized linear model, and critical values for classifying sub-test performance into equivalent scores. Six scores were derived from the performance of 194 normal subjects (MMSE score, range 27-30, mean 29.5 ± 0.5) divided per decade (from 20 to 90), per gender and per level of education (4 levels: 3-5, 6-8, 9-13, >13 years): immediate free recall (IFR), immediate total recall (ITR), recognition phase (RP), delayed free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. This study confirms the effect of age and education, but not of gender on immediate and delayed free and cued recall. The Italian version of the FCSRT-16 can be useful for both clinical and research purposes.