Baseline TGF-ß correlates with protection after immunization with Plasmodium falciparum sporozoites in the controlled human malaria infection model.

BACKGROUND: Here we assessed a possible relationship between baseline TGF-ß concentrations and acquisition of sterile immunity after Plasmodium falciparum sporozoite immunization. METHODS: TGF-ß concentrations were determined in samples of 65 malaria-naive volunteers in 4 studies either prior to and after challenge infection, or prior to and after first immunizing infection under chemoprophylaxis with P. falciparum sporozoites. RESULTS: High baseline TGF-ß concentrations were associated with rapid acquisition of sterile protection (p = 0.028). CONCLUSION: Baseline TGF-ß concentrations predict the efficiency of acquisition of sterile immunity following sporozoite immunization and may represent a steady-state regulatory mechanism to keep in check immune systems with a low threshold for activation.

Morbidity and costs of diverting ileostomy in transanal total mesorectal excision with primary anastomosis for rectal cancer.

BACKGROUND: The role of diverting ileostomy is debated in rectal cancer surgery with primary anastomosis. The aim of this study was to evaluate the associated morbidity and hospital costs of diversion after sphincter saving TaTME surgery. METHODS: All patients undergoing TaTME with primary anastomosis for rectal cancer between January 2012 and December 2019 in a single centre in the Netherlands were included. Patients with diverting ileostomy creation during primary surgery were compared with those without ileostomy. Outcomes included length of hospital stay, anastomotic leakage rates and total hospital costs at 1 year. RESULTS: One hundred and one patients were included in the ileostomy group, and 46 patients were in the non-ileostomy group. The number of female patients was 31 (30.7%) in the ileostomy group and 21 (45.7%) in the non-ileostomy group Mean age was 64.5 ± 11.1 years in the ileostomy group and 62.6 ± 10.7 years in the non-ileostomy group The anastomotic leakage rate was 21.7% in the non-ileostomy group and 15.8% in the ileostomy group (p = 0.385). The grade of leakage and number of anastomotic takedowns did not differ between groups. Mean costs at 1 year after surgery was €26,500.13 in the ileostomy group and €16,852.61 in the non-ileostomy group. The main cost driver was longer total length of hospital stay at 1 year (mean 12.4 ± 13.3 days vs 20.6 ± 12.6 days, p = 0.000). CONCLUSIONS: Morbidity and associated costs after diverting ileostomy are high. The incidence and morbidity of anastomotic leakage was not reduced by creation of an ileostomy. Omission of a diverting ileostomy after TaTME could possibly result in a reduction in treatment associated morbidity and costs.

[Guideline 'Ingrown toenails']. / Richtlijn 'Ingegroeide teennagel'.

Ingrown toenails (also called unguis incarnatus) are a common problem in the general population. In early 2020, the medical specialists' guideline "Ingrown toenail" was published in which the various treatment options are compared. Conservative treatment can be considered for stage I ingrown toenails. In stage II-III ingrown toenails and failing conservative treatment, operative treatment is recommended consisting of partial nail extraction from the ingrown nail edge in combination with destruction of the corresponding part of the matrix. There doesn't seem to be any reason to deviate from the advice in the case of a recurring ingrown toenail or an ingrown toenail in a patient with expected wound healing problems. A detailed elaboration of the guideline, which also contains a step-by-step operative approach, can be found on the Guidelines database (https://richtlijnendatabase.nl/).

Minimally invasive transanal surgery is safe after incomplete polypectomy of low risk T1 rectal cancer: a systematic review.

AIM: In patients who have undergone a polypectomy of a malignant rectal polyp without histopathological risk factors other than an involved or unclear resection margin, additional local excision is often performed. Evidence to support this approach is lacking. The aim of this systematic review and meta-analysis was to determine the outcome in terms of local recurrence, disease-free survival (DFS) and overall survival (OS) of additional local excision following incomplete polypectomy for low risk T1 rectal cancer. METHODS: A comprehensive search for published studies was performed. Only studies in which there was incomplete (or ≤ 1 mm) removal of pT1 rectal polyps or in which the resection plane could not be assessed were included. For each included study data on tumour stage, histological factors, surgical technique, local recurrence rate, 5-year DFS and 5-year OS were extracted. The PROSPERO registration number is CRD42017062702. RESULTS: A total of 580 studies were retrieved by the search in the MEDLINE database, Embase and the Cochrane Library. After careful appreciation, four studies were included in the analysis, comprising 102 patients of whom the majority had undeterminable (Rx) resection margins. Local excision via transanal endoscopic microsurgery was reported most frequently. Only 1% of patients developed a local recurrence. One study reported 5-year DFS and 5-year OS of 96% and 87% respectively. CONCLUSION: This study supports the use of additional local excision techniques for rectal cancer patients who underwent an incomplete polypectomy for a malignant rectal polyp in the absence of risk factors other than an uncertain resection margin.

Experimental study of radioimmunotherapy versus chemotherapy for colorectal cancer.

BACKGROUND: Radioimmunotherapy (RIT) has been shown to reduce the incidence of local recurrence of colorectal cancer in an experimental model. The aim of the present study was to investigate the survival benefit of RIT compared with chemotherapy. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of CC531 tumour cells. The therapeutic efficacy of (177) Lu-labelled MG1 (single intravenous dose of 300 MBq/kg, n = 20) was compared with that of 5-fluorouracil-based chemotherapy (6 weekly cycles administered intraperitoneally, n = 20) and no treatment (n = 20). The primary endpoint was survival. Toxicity was monitored by bodyweight measurement. RESULTS: Both chemotherapy and RIT affected bodyweight, but the weight of animals in the RIT group remained significantly higher than in the chemotherapy group (median slope of bodyweight plot 0·48 versus 0·30 g/day; P < 0·001). Kaplan-Meier analysis showed that overall survival in the RIT and chemotherapy groups was significantly better than that in the control group (50 and 46 per cent versus 25 per cent respectively after 170 days; P = 0·024 and P = 0·029). Survival after treatment with RIT did not differ from that after chemotherapy (P = 0·911). CONCLUSION: RIT is as effective as chemotherapy in experimental colorectal cancer.

Distensibility of forearm veins in haemodialysis patients on duplex ultrasound testing using three provocation methods.

OBJECTIVE: It is well-known that vasodilatator function is affected in patients with renal failure. We hypothesized impaired venous forearm distensibility in haemodialysis patients. The purpose of this study was to investigate which provocation method generated 'maximal' venous distensibility in the forearm of haemodialysis patients compared to healthy volunteers by using duplex ultrasound. DESIGN: The study group consisted of haemodialysis patients (n=30) and healthy volunteers (n=30). In each participant ultrasound measurements of the venous diameter were performed by using 3 different provocation methods. METHODS: The applied provocation methods were: 1) hydrostatic pressure, 2) venous congestion and 3) hydrostatic pressure and warmth. Significance of differences in mean diameter changes within the groups was assessed with the paired t-test. Significance of differences in mean diameter changes between the groups was compared by using multivariate regression analysis. RESULTS: In haemodialysis patients, the increase in mean diameter after the different methods was: 29% after methods 2 versus 1, 23% after methods 3 versus 2 and 59% after methods 3 versus 1. In healthy volunteers, the mean diameter increase was: 27% after methods 2 versus 1, 29% after methods 3 versus 2 and 64% after methods 3 versus 1. The greatest increase in the mean internal venous diameter among the haemodialysis patients and the healthy volunteers was after the provocation method which combined hydrostatic pressure with warmth (mean difference: 1mm, 95% CI: .57, 1.36; P<.001 and mean difference: 1.4mm, 95% CI: .88, 1.78; P<.001, respectively). After adjustment for the baseline variables, both groups demonstrated a non-significant mean diameter difference for each of the provocation methods. CONCLUSION: Hydrostatic pressure combined with warmth generates the greatest venous distensibility in the lower arm in haemodialysis patients in a sitting position and is not significantly different compared to healthy volunteers. Without the superior provocation method, venous diameters of haemodialysis patients can be assessed as false-negatives yielding that a primary radio cephalic arteriovenous fistula (RCAVF) at wrist level (the first choice) in these patients will be withheld.

Radioimmunotherapy prevents local recurrence of colonic cancer in an experimental model.

BACKGROUND: Radioimmunotherapy (RIT) is suitable for the treatment of microscopic residual disease and might therefore have an adjuvant role after colonic cancer surgery. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of 2 x 10(6) CC531 tumour cells. The biodistribution of (111)In-labelled MG1 monoclonal antibody was assessed after intraperitoneal administration. The therapeutic efficacy of (177)Lu-labelled MG1 (74 MBq per rat), administered on the day of surgery (D0, n = 13) or 5 days later (D5, n = 13), was compared with that of carrier only (n = 13). The primary endpoint was perianastomotic tumour growth 28 days after surgery. RESULTS: (111)In-labelled MG1 preferentially accumulated in perianastomotic CC531 tumours. RIT resulted in a transient reduction in bodyweight in both treatment groups compared with controls, but there were no other signs of clinical discomfort. No macroscopic or microscopic perianastomotic tumour growth was found in eight of 11 animals in the D0 group and 11 of 13 in the D5 group, whereas 11 of 13 controls had macroscopic tumour (P = 0.011 and P = 0.001 respectively). CONCLUSION: This study suggests that RIT may be an effective adjuvant treatment for preventing local recurrence after resection of colonic cancer.

Immunosuppression should be stopped in patients with renal allograft failure.

Patients returning to haemodialysis or peritoneal dialysis after a failed kidney transplantation sometimes have a renal allograft left in situ for some urine production. Low-dose immunosuppressive medication is often continued in such patients. To evaluate the morbidity and mortality between patients in time periods with (group A) or without (group B) low-dose maintenance immunosuppression, the present study was initiated. In a multi-centre cohort study we analysed data from patient files, which showed failure after at least 3 months graft function between 10 August 1972 and 4 April 1996, including 197 kidney transplantations. A total of 1.7 versus 0.51 infections per patient year was found in groups A and B, respectively (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 2.5-4.5). There was an increased mortality in group A compared to group B (OR 3.4, 95% CI: 1.8-6.3), both from infectious disease (OR 2.8, 95% CI: 1.1-7.0), and cardiovascular disease (OR 4.9, 95% CI: 1.8-13.5). Continuation of immunosuppressive medication did not lead to fewer rejections (defined as a painful, tender graft and/or haematuria and/or low-grade non-infectious fever). Transplantectomy-related morbidity and mortality were acceptable. The increase in morbidity and mortality associated with low-dose maintenance immunosuppression argues in favour of stopping these medicaments when failed renal allograft patients return to dialysis.

Implementing a stress management training: comparative trainer effectiveness.

Participants who were recruited from various organizations were randomly assigned to 1 of 2 stress management training (SMT) conditions or an assessment-only control group. The groups in the 1st SMT condition were led by external clinical psychologists. The groups in the 2nd SMT condition were led by individuals who held posts within the organizations involved, referred to as paraprofessionals. Results show favorable effects of the SMT program both in the short term as well as at 6-month follow-up. Results showed no serious differences in effectiveness between trainers. It is argued that, to be effective, the SMT program does not necessarily have to be given by clinical psychologists only but may instead be given by individuals from other professional orientations.

A comprehensive model of stress. the roles of experienced stress and neuroticism in explaining the stress-distress relationship.

BACKGROUND: In this study, a complex theoretical model regarding the stress-distress relationship was evaluated. The various components in the model included experienced stress (daily hassles), psychological distress, neuroticism, problem-focused coping, avoidant coping, satisfaction with received social support and unassertiveness. On the basis of various previous findings, experienced stress was assumed to have a direct effect on psychological distress. In addition, neuroticism was assumed to have a direct effect on psychological distress as well as an indirect effect through its association with experienced stress, problem-focused coping, avoidant coping, satisfaction with social support and unassertiveness. Further, both problem-focused and avoidant coping were assumed to affect the level of psychological distress directly as well as indirectly through their influence on experienced stress. Similarly, satisfaction with social support was assumed to have a direct beneficial effect on psychological distress in addition to an indirect effect through its association with coping and experienced stress. Finally, unassertiveness was assumed to have a direct effect on psychological distress as well as an indirect effect through its influence on experienced stress and coping. METHODS: A covariance path analysis technique (LISREL) was used. RESULTS: A considerable predictive power of the model could be demonstrated. Experienced stress and neuroticism turned out to be most predictive of psychological distress. The effects of social support, coping and unassertiveness on psychological distress were seriously attenuated by their common association with neuroticism. CONCLUSION: Above all, the present findings underscore the need to investigate all variables that are expected to play a role simultaneously so as to be able to take their interdependency into account. It is argued that although such comprehensive models may be more difficult to interpret as of yet, they are likely to more closely resemble reality.

Improved bacteriological surveillance of haemodialysis fluids: a comparison between Tryptic soy agar and Reasoner's 2A media.

BACKGROUND: Accurate microbiological surveillance in haemodialysis centres is important as end-stage renal patients can suffer from pyrogenic reactions due to bacterial contamination of dialysis fluids. To evaluate the microbiological quality of haemodialysis fluids, special nutrient-poor culture techniques are necessary. Although the Association for the Advancement of Medical Instrumentation (AAMI) recommends Tryptic soy agar (TSA) as the standard agar, several studies have resulted in a general preference for Reasoner's 2A (R2A) agar, as it appeared to be more sensitive in demonstrating contamination of typical haemodialysis associated bacteria. In the Netherlands TSA is still used for culturing dialysate, while dialysis water is cultured on R2A. Therefore, the aims of our study were to evaluate bacterial yields of dialysis fluids on both media, and to qualify their use in routine microbiological monitoring within our haemodialysis centre. METHODS: Between April 1995 and March 1996, 229 samples of pre-treated and final purified dialysis water, and samples of dialysates were collected. The specimens were aseptically taken from the tap, various points of the reverse osmosis (RO) water-treatment system, and the effluent tubes of 32 bicarbonate haemodialysis machines. Samples of 0.1 ml were inoculated in duplicate on spread plates with TSA and R2A agars. After 10 days of incubation at 25+/-2 degrees C, the numbers of colonies were quantified. The ranges of spread were taken 0-100 and 0-200 colony-forming units per milliliter (c.f.u./ml). RESULTS: The R2A agar had significantly higher colony counts than TSA agar for both dialysis water and dialysates. Considering 100 c.f.u./ml as the upper allowable bacterial limit for all dialysis fluids, microbiological non-compliance (bacterial growth) would be missed in 16% when using only TSA media (TSA < or =100 c.f.u./ml and R2A >100 c.f.u./ml), while this was 3% when using only R2A (TSA >100 c.f.u./ml and R2A < or =100 c.f.u./ml, P<0.0001). Considering 200 c.f.u./ml as the upper limit, non-compliance would have been missed in 10% when using only TSA (TSA < or =200 c.f.u./ml and R2A >200 c.f.u./ml), and 2% when using R2A (TSA > 200 c.f.u./ml and R2A < or =200 c.f.u./ml, P = 0.0011). CONCLUSIONS: Microbiological surveillance of haemodialysis fluids, including pre-treated dialysis water samples collected from RO treatment systems, can be performed more precisely with R2A media than TSA, when incubated at 25+/-2 degrees C for 10 days.

Mannitol-induced acute renal failure.

Mannitol is widely used because of its osmotic diuretic action and its presumed antioxidant properties. In pre-existent renal dysfunction, however, mannitol may accumulate leading to potentially deleterious effects. We describe a 71-year-old woman with moderate chronic renal failure due to diabetic nephropathy who developed acute anuric renal failure after mannitol administration for post-traumatic reflex sympathetic dystrophy. After haemodialysis symptoms of acute renal failure rapidly disappeared with recovery of pre-existent renal function. Daily measurement of the osmolal gap as a simple and accurate way of monitoring patients receiving mannitol infusion is emphasized. A rapid increase in the osmolar gap should prompt adjustment of the dose or even discontinuation of mannitol, especially in the case of pre-existent risk factors.

The Survey of Recent Life Experiences: a psychometric evaluation.

Hitherto, various critics have claimed that the most commonly used measure for daily hassles is confounded with psychological well-being in both content and format. In order to circumvent such contamination, the Survey of Recent Life Experiences (SRLE) was developed by Kohn and MacDonald (1992). In the present study, the SRLE was psychometrically evaluated within a general sample of the Dutch population. Confirmatory factor analysis showed that, with the exception of one item, the original six-factor structure was strongly replicated. For five of six factors, internal consistency reliabilities proved satisfactory. It is argued that the rather low internal consistency reliability of the sixth factor may be improved if additional items are subjoined. In addition, yielded relationships between the SRLE and other variables were in accordance with previous research. It is therefore argued that the results are in support of cross-cultural construct validity of the SRLE. Future use within other Western European societies is recommended.

'Oversaturation' of transferrin after intravenous ferric gluconate (Ferrlecit(R)) in haemodialysis patients.

BACKGROUND: Chronic haemodialysis causes blood loss and iron-deficiency. This can be corrected with intravenous preparations, e.g. sodium ferric-gluconate (FeGl). In two patents complaints of hypotension and malaise during FeGl infusion coincided with high levels of serum iron and a calculated transferrin iron saturation above 100%. Iron toxicity could be the cause of these complaints. Free iron is known to aggravate the toxicity of free radicals and other reactive oxygen products that are constantly formed in the body. We compared four rates of FeGl infusion with regard to iron parameters. METHODS: 20 dialysis patients received a total of 26 infusions of FeGl. A rapid infusion of 135 mg (Protocol A (n=10)) or 62.5 mg (Protocol B (n=7)) of FeGl was given during the last 30 min of dialysis. A slow infusion of 125 mg (Protocol C (n=9)) or 62.5 mg (Protocol D (n=10)) was given during 4 or 4.5 h of dialysis. Blood was taken at regular intervals, before, during, and after dialysis for determination of serum iron, transferrin, ferritin, haematocrit, total protein, albumin, and lactate dehydrogenase (LDH). Transferrin saturation was calculated from transferrin and serum iron. RESULTS: With rapid infusion A (125 mg) the highest levels of serum iron (median 120 (range 40-159) micromol/l) and transferrin saturation (207 (84-331)%) were seen at the end of the infusion. These were significantly higher than the peak levels with B, C, and D (P

Folic acid treatment of hyperhomocysteinemia in dialysis patients.

We measured fasting total plasma homocysteine (Hcy) in 10 chronic hemodialysis (HD) and 10 chronic peritoneal dialysis (PD) patients. Mean (+/- SEM) Hcy was 55.7 +/- 10.1 and 50.5 +/- 14.3 mumol/l, respectively (normal range 6-19 mumol/l). Hemodialysis treatment lowered Hcy by about 30%. Daytime Hcy concentrations were stable in the PD patients. Six weeks of treatment with folic acid (FA) significantly lowered Hcy in HD and PD patients to 24.0 +/- 1.8 and 21.0 +/- 3.6 mumol/l, respectively. After withdrawal, Hcy rose slowly, in parallel with the gradually decreasing plasma FA concentrations, which were greatly elevated during treatment. Chronic treatment with FA of another group of patients showed a similar effect on Hcy. Preliminary results of oral methionine loading in chronic dialysis patients were compatible with delayed homocysteine metabolism via the transsulfuration pathway. Further studies on the optimal treatment of hyperhomocysteinemia in chronic dialysis patients are needed.