Neutrophil-Lymphocyte Ratio and Absolute Lymphocyte Count as Prognostic Markers in Patients Treated with Curative-intent Radiotherapy for Non-small Cell Lung Cancer.

AIMS: The neutrophil-lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival. MATERIALS AND METHODS: A retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 2014 to 1 October 2016. A multivariate analysis was carried out to assess the ability of pre-treatment NLR/ALC, post-treatment NLR/ALC and change in NLR/ALC, adjusted for confounding factors using the Cox proportional hazards model, to predict disease recurrence and overall survival within 2 years of treatment. RESULTS: In total, 425 patients were identified with complete blood parameter values. None of the NLR/ALC parameters were independent predictors of disease recurrence. Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. Receiver operator curve analysis found a pre-NLR > 2.5 (odds ratio 1.71, 95% confidence interval 1.06-2.79, P < 0.05), a post-NLR > 5.5 (odds ratio 2.36, 95% confidence interval 1.49-3.76, P < 0.001), a change in NLR >3.6 (odds ratio 2.41, 95% confidence interval 1.5-3.91, P < 0.001) and a post-ALC < 0.8 (odds ratio 2.86, 95% confidence interval 1.76-4.69, P < 0.001) optimally predicted poor overall survival on both univariate and multivariate analysis when adjusted for confounding factors. Median overall survival for the high-versus low-risk groups were: pre-NLR 770 versus 1009 days (P = 0.34), post-NLR 596 versus 1287 days (P ≤ 0.001), change in NLR 553 versus 1214 days (P ≤ 0.001) and post-ALC 594 versus 1287 days (P ≤ 0.001). CONCLUSION: NLR and ALC, surrogate markers for systemic inflammation, have prognostic value in NSCLC patients treated with curative-intent radiotherapy. These simple and readily available parameters may have a future role in risk stratification post-treatment to inform the intensity of surveillance protocols.

Predicting the Risk of Disease Recurrence and Death Following Curative-intent Radiotherapy for Non-small Cell Lung Cancer: The Development and Validation of Two Scoring Systems From a Large Multicentre UK Cohort.

AIMS: There is a paucity of evidence on which to produce recommendations on neither the clinical nor the imaging follow-up of lung cancer patients after curative-intent radiotherapy. In the 2019 National Institute for Health and Care Excellence lung cancer guidelines, further research into risk-stratification models to inform follow-up protocols was recommended. MATERIALS AND METHODS: A retrospective study of consecutive patients undergoing curative-intent radiotherapy for non-small cell lung cancer from 1 October 2014 to 1 October 2016 across nine UK trusts was carried out. Twenty-two demographic, clinical and treatment-related variables were collected and multivariable logistic regression was used to develop and validate two risk-stratification models to determine the risk of disease recurrence and death. RESULTS: In total, 898 patients were included in the study. The mean age was 72 years, 63% (562/898) had a good performance status (0-1) and 43% (388/898), 15% (134/898) and 42% (376/898) were clinical stage I, II and III, respectively. Thirty-six per cent (322/898) suffered disease recurrence and 41% (369/898) died in the first 2 years after radiotherapy. The ASSENT score (age, performance status, smoking status, staging endobronchial ultrasound, N-stage, T-stage) was developed, which stratifies the risk for disease recurrence within 2 years, with an area under the receiver operating characteristic curve (AUROC) for the total score of 0.712 (0.671-0.753) and 0.72 (0.65-0.789) in the derivation and validation sets, respectively. The STEPS score (sex, performance status, staging endobronchial ultrasound, T-stage, N-stage) was developed, which stratifies the risk of death within 2 years, with an AUROC for the total score of 0.625 (0.581-0.669) and 0.607 (0.53-0.684) in the derivation and validation sets, respectively. CONCLUSIONS: These validated risk-stratification models could be used to inform follow-up protocols after curative-intent radiotherapy for lung cancer. The modest performance highlights the need for more advanced risk prediction tools.

Validation of an Arabic version of an instrument to measure waterpipe smoking behavior.

OBJECTIVES: Reliable and valid measures of waterpipe smoking are essential to study its health effects. The purpose of this study was to examine the reliability and validity of an Arabic translation of Maziak questionnaire that assesses various aspects of waterpipe smoking in epidemiological studies. STUDY DESIGN: A cross-sectional study. METHODS: This questionnaire was translated, back translated, and culturally adapted to the local Arabic dialect. Construct and convergent validity were assessed in a sample of 119 daily waterpipe smokers (WPS) and 30 occasional WPS, defined as smoking at least one waterpipe per week but less than daily from Beirut and Doha (mean age = 52.4 years, males = 61.7%). Construct validity was assessed by comparing the smoking behavior of daily and occasional WPS. Convergent validity was assessed by correlating daily smoking intensity ('number of waterpipe smoked per day') with 'number of waterpipe smoked yesterday' and by correlating lifetime smoking exposure (waterpipe-year) calculated by multiplying number of waterpipe smoked per day × duration of waterpipe smoking with alternate measures obtained graphically (graphical waterpipe-year) or adjusted (adjusted waterpipe-year). Criterion validity was assessed by correlating daily smoking intensity and lifetime smoking exposure with serum cotinine level. Test-retest reliability was analyzed by re-administering the questionnaire to 30 daily and 30 occasional WPS after 2 weeks. RESULTS: Smoking intensity, patterns of use, and willingness to quit differed significantly between daily and occasional WPS. Daily smoking intensity correlated strongly with the number of waterpipe smoked yesterday (rs = 0.68, P < 0.001), but not in the occasional WPS (rs = 0.13, P = 0.70). Waterpipe-year correlated very strongly with adjusted waterpipe-year and graphical waterpipe-year (rs = 0.98, P < 0.001 and rs = 0.92, P < 0.001, respectively). Waterpipe-year, daily smoking intensity, and number of waterpipe smoked yesterday, correlated weakly but significantly with serum cotinine levels (rs = 0.243, P = 0.01; rs = 0.359, P < 0.01 and rs = 0.387, P < 0.01, respectively). The type and pattern of waterpipe use items showed high test-retest reliability with near perfect agreement (k > 0.9), the sharing and intention to quit waterpipe items had substantial agreement (k > 0.6), and the intent to quit item showed moderate agreement (k > 0.4). CONCLUSION: The questionnaire showed strong reliability, face validity, construct and convergent validity, and a weak but statistically significant criterion validity. Maziak questionnaire is valid and reliable for assessing waterpipe smoking patterns, intensity, and willingness to quit.

Conversional surgery: single-step conversion of laparoscopic adjustable gastric band to laparoscopic sleeve gastrectomy.

BACKGROUND: Although some patients attain good outcomes after adjustable gastric band (LAGB), a certain quantity have experienced complications and insufficient weight loss. The objective of this study is to assess the safety and outcome of laparoscopic sleeve gastrectomy (LSG) as a conversion surgery after a failed LAGB. METHODS: This is a retrospective analysis of 40 patients who received LSG as conversional surgery from 2009 to 2012 in Al Amiri Hospital, Kuwait. Data analyzed included percentage of excessive weight loss (EWL%), body mass index (BMI), and postoperative complications. Paired t test was utilized to evaluate total weight loss after both procedures. RESULTS: Among the 40 patients that underwent conversion surgery, the mean age was 36 years old, 34 (85 %) of which were females. Follow-up for LAGB was 1 to 11 years (median, 4.5 years) and 6 months to 3 years (median, 1 year) for LSG. Mean BMI before LAGB was 44 kg/m(2) (SD = 7.2) and mean weight was 117.2 kg (SD = 25.1). A percentage of 20 % achieved good outcomes and 7.5 % experienced complications and 60 % insufficient weight loss. Median EWL% achieved with LAGB was 11.5 %, and after LSG, a median EWL% of 56.9 % was recorded. After conversional surgery, a significant drop in BMI was noted with p value < 0.002. CONCLUSIONS: Laparoscopic conversion from LAGB to LSG may be considered as an alternative for patients with a failed LAGB procedure. However, a longer follow-up study is required to validate the results.

Does hospitalization for asthma and allergic diseases occur more frequently in Ramadan fasting: a population based study (2000-2004).

OBJECTIVE: Over one billion Muslims fast worldwide during the month of Ramadan. Fasting during Ramadan is a radical change in life style for the period of a lunar month. Our objective in this study was to investigate whether Ramadan fasting has any effect on the incidence of asthma and to assess whether Ramadan Fasting affected normal lung function values. DESIGN: This is a hospital-based cohort study. SETTING: Hamad General Hospital, Hamad Medical Corporation, Doha, State of Qatar. PATIENTS: We prospectively reviewed 1590 asthmatic Muslim patients who were hospitalized with asthma over a four year period from January 2000 to December 2004. Patients were divided according to the time of presentation in relation to the month of Ramadan, one month before, during and one month after Ramadan. METHODS: Pulmonary function tests were performed on an electronic spirometer (Compact Vitalograph, Buckingham, U.K.). Performance of the spirometric test and data collection were according to as described by the American Thoracic Society. RESULTS: There were 1590 patients studied. Among them, 901 were males (56.7%) and 689 were females (43.3%). Their mean age was 30 years (15-60). All patients expressed clinical allergy, 454 patients (28.6%) had asthma and rhinitis, 513 patients (32.3%) had allergic rhinitis, 300 patients (18.9%) had asthma alone and 10.6% had other allergic conditions. The ventilatory capacity of lung function parameters mean did not show any statistically significant differences between a period of pre-Ramadan, during Ramadan and after Ramadan concerning FVC, FEV1, FEF(25-75) FEV1/FVC, and PEF values. CONCLUSION: This study demonstrated that no significant difference was found in number of hospitalization and the mean spirometric values for asthma while fasting during the month of Ramadan when compared to the non-fasting months.

Post-translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface.

Annexin A1 (ANXA1) has an important role in cell-cell communication in the host defense and neuroendocrine systems. In both systems, its actions are exerted extracellularly via membrane-bound receptors on adjacent sites after translocation of the protein from the cytoplasm to the cell surface of adjacent cells. This study used molecular, microscopic, and pharmacological approaches to explore the mechanisms underlying the cellular exportation of ANXA1 in TtT/GF (pituitary folliculo-stellate) cells. LPS caused serine-phosphorylation of ANXA1 (ANXA1-S27-PO4) and translocation of the phosphorylated protein to the cell membrane. The fundamental requirement of phosphorylation for membrane translocation was confirmed by immunofluorescence microscopy on cells transfected with wild-type or mutated (S27/A) ANXA1 constructs tagged with enhanced green fluorescence protein. The trafficking of ANXA1-S27-PO4 to the cell surface was dependent on PI3-kinase and MAP-kinase. It also required HMG-coenzyme A and myristoylation. The effects of HMG-coenzyme A blockade were overcome by mevalonic acid (the product of HMG-coenzyme A) and farnesyl-pyrophosphate but not by geranyl-geranylpyrophosphate or cholesterol. Together, these results suggest that serine-27 phosphorylation is essential for the translocation of ANXA1 across the cell membrane and also identify a role for isoprenyl lipids. Such lipids could target consensus sequences in ANXA1. Alternatively, they may target other proteins in the signal transduction cascade (e.g., transporters).

Postanaesthetic shivering--a new look at tramadol.

We studied whether tramadol administered at the time of wound closure can prevent postanaesthetic shivering. One hundred and fifty patients scheduled for general anaesthesia and surgery were randomly allocated and tramadol was administered intravenously at a dose of 2 mg.kg(-1) in the high-dose group, 1 mg.kg- in the low-dose group and 0.9% saline in the control group. In the high-dose group, 2% of patients had postanaesthetic shivering, compared to 4% in the low-dose group and 48% in the control group (p < 0.001 vs. tramadol groups). There was no delay in tracheal extubation after reversal of neuromuscular blockade. The incidence of adverse side-effects such as sedation and vomiting did not differ statistically and were clinically not significant. This study strongly supports the use of tramadol at wound closure for prevention of postanaesthetic shivering.

Fireworks injury: temporal bone penetration and a wooden intra-cranial foreign body.

We describe a case of a teenager sitting in a car, who was struck by a fireworks missile. The unusual presentation of a large wooden foreign body penetrating through the temporal bone and lodging in the brain is detailed. The management is discussed.

Myocardial infarction with normal coronary angiography compared with severe coronary artery disease without myocardial infarction: the crucial role of smoking.

BACKGROUND: Why do some patients suffer acute myocardial infarction (MI) despite angiographically normal coronary arteries (NL + MI) whereas others enjoy an acute MI-free life despite extensive three-vessel disease (3VD-MI)? The present study contrasts these two groups to identify some differences in the risk profile. METHODS: In 10,000 patients admitted to the cardiology service, a first MI was confirmed in 2356 patients, of whom 1609 underwent coronary angiography. In 77 patients with MI, coronary angiography was found to be entirely normal (NL + MI, 77/1609, 4.1%). These were contrasted to 123 patients with severe three-vessel coronary disease but no MI (3VD-MI). RESULTS: Patients with NL + MI were 13 years younger (42 +/- 8.3 vs 55 +/- 10.5, P < 0.05), with 33 patients (43%) under the age 40 years, in contrast to only 9 patients (7.3%) in the 3VD group being this age. Patients with NC + MI were more often current smokers (80.5% vs 29% in the 3VD group; P < 0.01). Patients with 3VD-MI were, on the other hand, more often diabetic (54% vs 9% in the NL + MI group; P < 0.01) and had a higher cholesterol level (5.6 +/- 1.1 vs 4.9 +/- 1.0 Mmol/l, P < 0.01) as well as a higher incidence of chronic stable angina (52% vs 22%; P < 0.01) and heart failure (6% compared with 0% in the NL + MI group). Sixty-one out of 77 (79%) NL + MI patients had a single risk factor, and in 87%, this was smoking alone. Diabetes mellitus was rare and never occurred alone in this group. CONCLUSION: In patients who suffer MI despite normal coronary angiography, smoking is a major risk factor: In contrast, in patients with extensive coronary artery disease on angiography but no MI, diabetes rather than smoking is the dominant risk factor. The findings of this study support the view that the risk factors for stable and unstable coronary artery disease are different, as reflected by the contrast of the above groups at the extremes of the spectrum. Smoking appears to be a major risk factor for acute MI (even with normal coronary angiography), whereas diabetes is a major risk factor for more severe but more stable coronary artery disease.

Acid-stimulated phosphate uptake by activated sludge microorganisms under aerobic laboratory conditions.

Activated sludge inocula taken from five different wastewater treatment plants were grown aerobically under laboratory conditions on mineral salts medium containing either glucose or skimmed milk powder as carbon source. Cultures showed increases of between 50% and 143% in levels of phosphate uptake from the medium when the growth pH was 5.5 rather than 7.5. Of 100 individual sludge microbial isolates studied, 34 demonstrated such acid-stimulated luxury phosphate uptake; the optimum pH for the process was shown to lie between 5.0 and 6.5. Enhanced phosphate removal by these isolates was accompanied by increases of between 2 and 10.5-fold in their polyphosphate content; this was visualised as intracellular inclusions. Acid-stimulated luxury phosphate uptake by environmental microorganisms is a previously-unrecognised phenomenon that may have application in novel technologies for nutrient removal from wastewaters.

Regulation of the hypothalamo-pituitary-adrenal axis by cytokines.

Many of the pro-inflammatory cytokines which are released in response to immune/inflammatory insults exert marked stimulatory influences on the hypothalamo-pituitary-adrenocortical (HPA) axis; they thus provoke the release of glucocorticoids which, in turn, temper the ensuing immune-inflammatory response and thereby complete a homeostatic neuroendocrine-immune regulatory loop. This article reviews the putative mechanisms by which cytokines, released acutely in response to such insults, activate the HPA axis, placing particular emphasis on the actions and interactions of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6) and on the counter-regulatory mechanisms that are in place.

Sex differences in circulating human leptin pulse amplitude: clinical implications.

Leptin, a product of fat cells, provides a signal of nutritional status to the central nervous system. Leptin concentrations have ultradian and diurnal fluctuations. We conducted this study to assess sex differences in the levels of organization of frequently sampled leptin concentrations in healthy, normal weight women and men. Leptin levels were sampled every 7 min for 24 h in 14 healthy, normal weight individuals (6 women and 8 men). The 14 leptin time series containing a total of 2898 leptin measurements were assessed by 1) algorithms that characterize statistically significant pulsatility, 2) Spectral (Fourier) analysis, 3) analysis of time intervals and variability, and 4) approximate entropy. We found that frequently sampled plasma leptin concentrations have a 24-h profile that is numerically more than twice as high in women as in men, and leptin pulse amplitude is likewise more than twice as high in women. However, healthy men and women have nearly identical concentration-independent and frequency-related 24-h and ultradian patterns. Leptin concentrations have nonrandom fluctuations over 24 h, independent of their absolute value and underlying 24-h periodicity, that are similar in men and women. Ultradian periodicities detected by Fourier time series have similar values in men and women. The strongest distinction between the sexes in the level of organization of leptin concentration is not at the level of pulse organization or oscillation frequency, but, rather, in the mass or amount of leptin released (or removed) per unit time, indicating that women might be more resistant to the effects of leptin than men. Because leptin is clinically relevant to the regulation of body weight, future studies should examine whether the relative leptin resistance exhibited by women might contribute to their increased susceptibility to disorders whose pathophysiology involves dysregulation of food intake and body weight.

Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women.

Leptin, an adipocyte hormone, is a trophic factor for the reproductive system; however, it is still unknown whether there is a dynamic relation between fluctuations in circulating leptin and hypothalamic-pituitary-ovarian (HPO) axis hormones. To test the hypothesis that fluctuations in plasma leptin concentrations are related to the levels of luteinizing hormone (LH) and estradiol, we sampled plasma from six healthy women every 7 min for 24 h during days 8-11 of the menstrual cycle. Cross-correlation analysis throughout the 24-h cycle revealed a relation between release patterns of leptin and LH, with a lag of 42-84 min but no significant cross-correlation between LH and estradiol. The ultradian fluctuations in leptin levels showed pattern synchrony with those of both LH and estradiol as determined by cross-approximate entropy (cross-ApEn). At night, as leptin levels rose to their peak, the pulsatility profiles of LH changed significantly and became synchronous with those of leptin. LH pulses were fewer, of longer duration, higher amplitude, and larger area than during the day. Moreover, the synchronicity of LH and leptin occurred late at night, at which time estradiol and leptin also exhibited significantly stronger pattern coupling than during the day. We propose that leptin may regulate the minute-to-minute oscillations in the levels of LH and estradiol, and that the nocturnal rise in leptin may determine the change in nocturnal LH profile in the mid-to-late follicular phase that precedes ovulation. This may explain the disruption of hypothalamic-pituitary-ovarian function that is characteristic of states of low leptin release, such as anorexia nervosa and cachexia.

Qualitative hepatic venous Doppler sonography versus portal flowmetry in predicting the severity of esophageal varices in hepatitis C cirrhosis.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of simple recognition of hepatic vein waveform abnormalities using Doppler sonography with portal Doppler flowmetry for the noninvasive assessment of esophageal varices in patients with hepatitis C cirrhosis. SUBJECTS AND METHODS: Fifty patients with biopsy-proven liver cirrhosis caused by hepatitis C who were being examined for possible liver transplantation were studied prospectively with Doppler sonography by a single observer. Hepatic vein waveforms were classified as normal triphasic, abnormal biphasic, monophasic, and those with loss of the reverse-flow component. Portal flow indicators included the maximum values of portal flow velocity, portal vein flow volume, diameter of the portal vein, and congestion index. For the purposes of this study, we simplified the endoscopic grading of varices by classifying F1 and F2 varices as small and F3 as large. None of the patients had clinical or echocardiographic signs of failure of the right side of the heart. RESULTS: Sensitivity for the detection of large varices was 92% for monophasic waves, 76% for waves with loss of the reverse flow component, and 62% for biphasic waves. Overall specificity was 100%. Portal vein diameter and congestion index were higher (p < .02) and portal vein velocity was lower (p < .05) in patients with varices than in patients without varices, but these indicators were not useful in determining the size of varices. Portal vein flow volume did not differ in the presence of varices or ascites and was independent of the morphology of the hepatic vein wave. CONCLUSION: Simple recognition of patterns seen in hepatic vein waveform morphology in patients with liver cirrhosis caused by hepatitis C is superior to portal Doppler flowmetry for predicting the size of esophageal varices.

Evidence for widespread asymptomatic Trypanosoma rhodesiense human infection in the Luangwa Valley (Zambia).

The RoTat 1/2 CATT test developed for Trypanosoma evansi was used in comparison with other diagnostic tests for the detection of T. rhodesiense infection in the northern part of the Luangwa Valley. The human population, the domestic and a large number of game animals were positive with the RoTat 1/2 CATT, the Ag-ELISA, the IFAT and the radioimmunoprecipitation tests. Human sera from these areas precipitated the same trypanosome-antigen components 35S-methionine labelled whereas few differences in band patterns were found between individual game animals. Surprisingly, however, T. rhodesiense could not be isolated from the "Ag-ELISA and radioimmunoprecipitation" positive patients from the Musenga and Kasyasya localities. The fact that the CATT positive humans were positive in antigen detection tests, does indicate that in all probability they carry or had been carrying a subpatent infection. These results suggest that the reservoir for T. rhodesiense in that region is considerable, comprising the game animals and probably to an even greater extent, the human population.

How do African game animals control trypanosome infections?

African trypanosomiasis is endemic over much of sub-saharan Africa. But whereas domestic animals - especially cattle - often succumb to the infection, wild mammals generally show a high degree o f resistance. Many species o f wildlife living in tsetse-infested areas carry trypanosome infections, and so act as important reservoir hosts, but generally show no obvious ill-effects. How they survive the infection is an important question in understanding mechanisms o f trypanotolerance, yet relevant data are sparse and scattered. Here, Ayub Mulla and Roy Rickman review some of the previous studies to illustrate how complex the question is.