The clinical features, treatment and prognosis of neutropenic fever and Coronavirus disease 2019 results of the multicentre teos study.

This multicentre (22 centres in Turkey) retrospective cohort study aimed to assess the clinical outcomes of patients with neutropenic fever and SARS-CoV-2 positivity. Study period was 15 March 2020-15 August 2021. A total of 170 cases (58 female, aged 59 ± 15.5 years) that fulfilled the inclusion criteria were included in the study. One-month mortality rate (OMM) was 44.8%. The logistic regression analysis showed the following significant variables for the mentioned dependent variables: (i) achieving PCR negativity: receiving a maximum of 5 days of favipiravir (p = 0.005, OR 5.166, 95% CI 1.639-16.280); (ii) need for ICU: receiving glycopeptide therapy at any time during the COVID-19/FEN episode (p = 0.001, OR 6.566, 95% CI 2.137-20.172), the need for mechanical ventilation (p < 0.001, OR 62.042, 95% CI 9.528-404.011); (iii) need for mechanical ventilation: failure to recover from neutropenia (p < 0.001, OR 17.869, 95% CI 3.592-88.907), receiving tocilizumab therapy (p = 0.028, OR 32.227, 95% CI 1.469-707.053), septic shock (p = 0.001, OR 15.4 96% CI 3.164-75.897), and the need for ICU (p < 0.001, OR 91.818, 95% CI 15.360-548.873), (iv) OMM: [mechanical ventilation (p = 0.001, OR 19.041, 95% CI 3.229-112.286) and septic shock (p = 0.010, OR 5.589,95% CI 1.509-20.700)]. Although it includes a relatively limited number of patients, our findings suggest that COVID-19 and FEN are associated with significant mortality and morbidity.

Evaluation of the effect of the COVID-19 pandemic on mucormycosis studies with bibliometric analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is a relatively new concept in the literature that emerged during the pandemic. Bibliometric analysis is a type of analysis that uses mathematical and statistical methods to study the formal properties of knowledge areas. This study aimed to reveal the main themes, conceptual structures, and trends of bibliometric studies on mucormycosis in 2 different periods, pre-and during the pandemic. METHODS: This study consisted of 2 periods: pre-COVID-19 and COVID-19. Articles were collected from the Web of Science (WOS) Core Collection database. We provided AND and OR connectors for the keyword query and selected studies based on relevant keywords. Collected data were classified based on their publication date and examined using the R programming language (Version 4.0.3) package Bibliometrix and SciMAT Software. RESULTS: A total of 1261 articles were investigated, and performance and information structure analyses were conducted. Based on Bradford's law, the Journal of Fungi was the top-ranked journal in both periods. Cureus and mycoses were placed 2nd and 3rd in the second period. India is the largest contributor. In performance analysis, conceptual structures such as Rhizopus oryzae, epidemiology, diagnosis, management, treatment, and outcomes were at the forefront of mucormycosis publications during the COVID-19 period. CONCLUSIONS: Research trends have shifted to the clinical treatment and management of COVID-19. Therefore, pathogenesis, diagnosis, follow-up, and treatment strategies for CAM should be developed in the future.

Surveillance of hemodialysis related infections: a prospective multicenter study.

As in many countries, there is neither a surveillance system nor a study to reveal the hemodialysis (HD) related infection rates in Turkey. We aimed to investigate the infection rate among HD outpatients and implement CDC's surveillance system. A multicenter prospective surveillance study is performed to investigate the infection rate among HD patients. CDC National Healthcare Safety Network (NHSN) dialysis event (DE) protocol is adopted for definitions and reporting. During April 2016-April 2018, 9 centers reported data. A total of 199 DEs reported in 10,035 patient-months, and the overall DE rate was 1.98 per 100 patient-months. Risk of blood culture positivity is found to be 17.6 times higher when hemodialysis was through a tunneled catheter than through an arteriovenous fistula. DE rate was significantly lower in patients educated about the care of their vascular access site. Staphylococcus aureus was the most causative microorganism among mortal patients. Outcomes of DEs were hospitalization (73%), loss of vascular access (18.2%), and death (7.7%). This first surveillance study revealed the baseline status of HD related infections in Turkey and showed that CDC National Healthcare Safety Network (NHSN) DE surveillance system can be easily implemented even in a high workload dialysis unit and be adopted as a nationwide DE surveillance program.

[Treatment with Intravenous Acyclovir Desensitization for Severe Acyclovir Allergy: A Case of Herpes Encephalitis]. / Ciddi Asiklovir Alerjisinde Intravenöz Asiklovir Desensitizasyon Tedavisi: Herpes Ensefaliti Olgusu.

Herpes simplex virus (HSV) is a sporadic viral encephalitis agent that causes high mortality and morbidity, accompanied by neurological dysfunction findings. Acyclovir is the only antiviral treatment option that should be initiated in all patients with suspected encephalitis as soon as possible. Acyclovir is rarely possible to cause allergic reactions. It may occur in a wide range from generalized cutaneous rash to Stevens-Johnson syndrome. A case of HSV-1 encephalitis who had no treatment option other than intravenous acyclovir and was successfully treated with intravenous desensitization was presented in this report. A 59-year-old male patient was admitted to the emergency department with complaints of high fever and altered consciousness. Diagnostic lumbar puncture was performed and intravenous acyclovir treatment was initiated empirically with the preliminary diagnosis of encephalitis. On the third day of the treatment, HSV type 1 polymerase chain reaction (PCR) was detected as positive. Acyclovir treatment was discontinued due to the development of a severe allergic reaction on the fifth day of acyclovir treatment. Allergic symptoms of the patient regressed with discontinuation of acyclovir treatment and application of concomitant methylprednisolone treatment. The intravenous acyclovir desensitization protocol was applied to the patient, and the patient was successfully treated. In this case, it has been shown that intravenous acyclovir desensitization can be applied in the treatment of life-threatening infections with no treatment options other than intravenous acyclovir. Our case is the first adult case in the literature to be treated with intravenous acyclovir desensitization.

Is the course of COVID-19 associated with tuberculin skin test diameter? A retrospective study.

The pathogenesis of coronavirus disease 2019 (COVID-19) is still not fully understood. As severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has a similar pathogenetic pathway to Mycobacterium tuberculosis, it has been reported that there may be a relationship between Bacille Calmette-Guérin (BCG) vaccination rate and COVID-19 severity. This study investigated the relationship between tuberculin skin test (TST) induration diameter and the clinical course of COVID-19. Of 1963 adult patients who underwent TST, 76 patients with SARS-COV-2 infection confirmed by RT-PCR analysis of respiratory tract samples were included in the study. Relationships between COVID-19 clinical severity and TST positivity, induration size, and other clinical parameters were analyzed. Of the 76 patients, TST results were negative for 53 patients (69.7%) and positive for 23 patients (30.3%). COVID-19 severity was mild in 47 patients (61.8%), moderate in 22 patients (28.9%), and severe in seven patients (9.3%). All TST-positive patients had mild disease. Patients with mild disease had a significantly higher TST positivity rate (p < 0.001) and larger induration diameter (p < 0.001). The area under the receiver operating characteristic (ROC) curve of TST induration size for the differentiation of mild with moderate and severe disease was 0.768 (p < 0.001). The maximum Youden J index value was 0.522 at an induration diameter of 6.5 mm, which had a sensitivity of 66.0% and specificity of 86.2%. COVID-19 patients with positive TST showed a significantly higher rate of mild disease than those with negative TST. TST positivity is favorably associated with the course of COVID-19.

Effects of short-term oral administration of dietary marine oils in patients with inflammatory bowel disease and joint pain: a pilot study comparing seal oil and cod liver oil.

BACKGROUND: Very long chain n-3 polyunsaturated fatty acids have modulating effects on inflammatory mechanisms. Seal and fish oils are rich in n-3 polyunsaturated fatty acids, and possibly therefore high doses of nasoduodenally administered seal oil rapidly relieved inflammatory bowel disease (IBD)-associated joint pain in two recent studies. In the present study, we compared the effects of short-term oral administration of seal oil and cod liver oil on IBD-related joint pain, leucotriene B(4) level, serum fatty acid profile and IBD activity. METHODS: Thirty-eight patients with IBD-related joint pain were included in the study; 21 had Crohn's disease and 17 ulcerative colitis. Ten milliters of seal oil (n=18) or cod liver oil (n=20) was self-administered orally 3 times a day for 14 days before meals in a double-blind setting. RESULTS: There were no significant differences between the two intervention groups or between Crohn's disease and ulcerative colitis patients. There was a tendency toward improvement in several joint pain parameters after both seal oil and cod liver oil administration. Further, plasma leucotriene B(4) concentration, serum Sigma n-6 to Sigma n-3, and arachidonic acid (20:4n-6) to eicosapentaenoic acid (20:5n-3) ratios were similarly reduced after administration of seal oil and cod liver oil. CONCLUSION: No significant differences in the two treatment groups were seen; in both groups, the changes in several joint pain parameters, leucotriene B(4) level of plasma, and serum fatty acid profile were putatively favourable.

Food hypersensitivity reactions visualised by ultrasonography and magnetic resonance imaging in a patient lacking systemic food-specific IgE.

BACKGROUND: Abdominal complaints related to food intake might be due to hypersensitivity. A firm diagnosis of food allergy is often difficult to establish, particularly in the absence of systemic food-specific IgE. Using ultrasonography and magnetic resonance imaging (MRI) we were able to visualise the intestinal response in one such case. METHODS: A 24-year-old female presented with self-reported food hypersensitivity, particularly related to the intake of egg. Nausea and diarrhoea were predominant symptoms. Double-blind placebo-controlled food challenge with raw egg was positive, but all other conventional tests of food hypersensitivity, including skin prick test, total and food-specific IgE in serum, were negative. A thorough investigation programme could not reveal any organic disease of the gastrointestinal tract. We extended the evaluation to include two new provocation tests, where intestinal wall thickening and the amount of luminal liquid were monitored by external abdominal ultrasound and MRI. RESULTS: Both ultrasound and MRI investigations indicated intestinal wall thickening and influx of large amounts of fluid into the proximal small intestines within 10 min of duodenal challenge with egg. The response was associated with abdominal pain and bloating. CONCLUSIONS: The response to provocation was typical of an immediate allergic reaction. Our results indicate that local food-induced hypersensitivity reactions can occur in the gut in the absence of systemic indications of IgE-mediated allergy. Abdominal ultrasonography and MRI might become valuable tools for documenting such responses.

Short-term duodenal seal oil administration normalised n-6 to n-3 fatty acid ratio in rectal mucosa and ameliorated bodily pain in patients with inflammatory bowel disease.

BACKGROUND: A high dietary intake of n-6 compared to n-3 fatty acids (FAs) may promote the production of pro-inflammatory eicosanoids and cytokines. In two recent studies, short-term (10-day) duodenal administration of n-3 polyunsaturated fatty acid rich seal oil ameliorated joint pain in patients with inflammatory bowel disease (IBD). Using unpublished data from these two studies we here investigated whether normalisation of the n-6 to n-3 FA ratio in blood and tissues by seal oil administration was associated with improved health related quality of life (HRQOL) as assessed by the generic short-form 36 (SF-36) questionnaire. RESULTS: In the first pilot study, baseline n-6 to n-3 FA ratio in rectal mucosal biopsies from 10 patients with IBD (9 of those had joint pain) was significantly increased compared with that in 10 control patients without IBD or joint pain. Following seal oil administration, the n-6 to n-3 FA ratio of the IBD-patients was significantly lowered to the level seen in untreated controls. In the subsequent, randomized controlled study (n = 19), seal oil administration reduced the n-6 to n-3 FA ratio in blood similarly and also the SF-36 assessed bodily pain, while n-6 FA rich soy oil administration had no such effect. CONCLUSION: In these two separate studies, short-term duodenal administration of seal oil normalised the n-6 to n-3 FA ratio in rectal mucosa and improved the bodily pain dimension of HRQOL of patients with IBD-related joint pain. The possibility of a causal relationship between n-6 to n-3 FA ratio in rectal mucosa and bodily pain in IBD-patients warrants further investigations.

Subjective health complaints and modern health worries in patients with subjective food hypersensitivity.

Perceived food hypersensitivity is much more common than food allergy as medically verified. Unexplained symptoms and wrong attribution are typical in subjective health complaints. We hypothesize that subjective health complaints and worries are abnormally prevalent among patients with subjective food hypersensitivity. Forty-six patients with subjective food hypersensitivity and two control groups, one formed by 50 health care workers and one by 70 sex- and age-matched volunteers from the general population, were included in our study. All filled in two questionnaires: Subjective Health Complaints Inventory and Modern Health Worries Scale. None of the patients had IgE-mediated food allergy. The patients scored significantly higher than the controls on sum scores for four domains of subjective health complaints, including gastrointestinal complaints (P < 0.001), musculoskeletal complaints (P < 0.01), "pseudoneurology" (P < 0.001), and allergy (P < 0.001). Sum scores on modern health worries did not differ significantly between groups. The results support our hypothesis of an association between subjective food hypersensitivity and subjective health complaints, corroborating the view that, in the absence of food allergy, the conditions are sharing pathogenetic mechanisms.

Low-dose oral ferrous fumarate aggravated intestinal inflammation in rats with DSS-induced colitis.

BACKGROUND: Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low-dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)-induced colitis in rats. METHODS: Forty male Wistar rats were divided into 5 groups: no intervention, sham gavage (distilled water), ferrous fumarate, DSS, and ferrous fumarate + DSS. Ferrous fumarate was dissolved in distilled water (0.60 mg Fe/kg per day) and administered by gavage on days 1 to 14. All rats were fed a standard diet. Colitis was induced by 5% DSS in drinking water on days 8 to 14. Rats were killed on day 16. Histologic colitis scores, fecal granulocyte marker protein, plasma malondialdehyde, plasma antioxidant vitamins, and plasma aminothiols were measured. RESULTS: DSS significantly increased histologic colitis scores (P < 0.001) and fecal granulocyte marker protein (P < 0.01). Ferrous fumarate further increased histologic colitis scores (P < 0.01) in DSS-induced colitis. DSS + ferrous fumarate decreased plasma vitamin A compared with controls (P < 0.01). Otherwise, no changes were seen in plasma malondialdehyde, plasma antioxidant vitamins, or plasma aminothiols. CONCLUSION: Low-dose oral ferrous iron enhanced intestinal inflammation in DSS-induced colitis in rats.

Response to intestinal provocation monitored by transabdominal ultrasound in patients with food hypersensitivity.

OBJECTIVE: Owing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be recognized by ultrasound. MATERIAL AND METHODS: Thirty-two patients with chronic abdominal complaints, self-attributed to food hypersensitivity/allergy were included in the study. Via a nasoduodenal tube, the duodenal mucosa was challenged with the suspected food item dissolved in 10 ml water or saline. Using external ultrasound, the sonographic features (wall thickness and diameter of the duodenal bulb and jejunum, peristalsis activity and luminal fluid) were recorded before and during one hour after challenge. RESULTS: Sonographic changes were observed after challenge in 14 (44%) of the 32 patients. A positive sonographic response (increased wall thickness, diameter, peristalsis and/or luminal fluid) was significantly related to a positive skin prick test (p = 0.008) and a positive double-blind placebo-controlled food challenge (p = 0.03). A significant correlation was found between provocation-induced symptoms and wall thickness of the duodenal bulb (r = 0.50, p = 0.004) or the jejunum (r = 0.42, p = 0.02). Intra- and interobserver variation of the tracing procedure showed low values. CONCLUSIONS: Responses of the proximal small intestines to direct provocation (swelling of the wall and exudation of fluid into the lumen) could be visualized by transabdominal ultrasound. This new provocation test could be helpful in the evaluation of patients with food hypersensitivity.

Food hypersensitivity-immunologic (peripheral) or cognitive (central) sensitisation?

Patients with food hypersensitivity suffer poor quality of life and several unexplained health complaints, both abdominal and extra-abdominal. Part of the suffering is due to healthcare providers' neglect and poor insight, allowing a strong position for alternative medicine. Distinguishing food allergy from functional and organic disorders can be extremely difficult. We have found examination of faecal calprotectin and gut permeability to be useful for excluding organic disease, whilst conventional provocation tests for positive diagnosis of food hypersensitivity are cumbersome. Our new ultrasound provocation test has been promising, but we acknowledge that much work remains to be done before its sensitivity and specificity can be finally established. The majority of patients with self-reported food hypersensitivity have a non-allergic hypersensitivity disorder. We suggest that cognitive-emotional sensitisation at the brain level, and not peripheral (immunological) sensitisation, is a major pathogenetic mechanism by which the patients' various abdominal and extra-abdominal health complaints are generated. Extensive activation of cognitive networks might be triggered by peripheral sensory mechanisms, often misinterpreted as 'food allergy'. Clearly, the approach to patients with food hypersensitivity should be interdisciplinary.

An acute stressor enhances sensitivity to a chemical irritant and increases 51CrEDTA permeability of the colon in adult rats.

We investigated the effect of prior acute stress on colonic permeability induced by a chemical irritant known to induce symptoms similar to inflammatory bowel disease in rodents. Adult male rats (n = 12) were stressed by a single session of ten unpredictable, uncontrollable foot shocks, and half were home cage controls (n = 12). Twenty-nine days later, half of each treatment group was exposed to 4% DSS (dextran sulphate sodium) solution in their drinking water for 48 hours while half received pure water over two periods separated by 17 days. After food deprivation overnight and light isoflurane anaesthesia the following morning, the animals were given a colonic infusion of 2000 nCi (nanocurie) 51CrEDTA (51Cr-labelled ethylenediaminetetraacetic acid) and then placed individually in metabolic cages for a six hours continuous urine collection. Radioactivity in urine was measured by a gamma counter and percentage recovery of 51CrEDTA calculated as an indicator of colonic mucosal permeability. Results concluded that pre-shocked animals exposed to DSS showed significantly higher mucosal permeability than the pre-shocked animals given water, and the non-shocked animals given either DSS or water. Pre-shock in combination with two exposures to a chemical irritant separated by 17 days had a pronounced effect on colonic permeability, indicating that stress should be considered a possible initiating or contributory factor to increased intestinal permeability related to a mucosal challenge.

Patients with subjective food hypersensitivity: the value of analyzing intestinal permeability and inflammation markers in gut lavage fluid.

BACKGROUND/AIM: Subjective food hypersensitivity is prevalent in the general population. The aim of this study was to seek objective evidence of food hypersensitivity by analyzing intestinal permeability and inflammation markers in gut lavage fluid. METHODS: Fifty-two patients with abdominal complaints self-attributed to food hypersensitivity were examined by skin prick test, serum IgE analysis, double-blind, placebo-controlled food challenge (DBPCFC), and intestinal lavage. The results were compared with those of 44 patients without food hypersensitivity. Neither the patients nor the controls had organic diseases that could explain their symptoms. Intestinal lavage was performed by administering 2 liters of isotonic polyethylene glycol (molecular weight 3,350 daltons) solution containing 50 microCi of [51Cr]EDTA through a nasoduodenal tube. The first clear fluid passed per rectum was collected and analyzed for histamine, eosinophilic cationic protein (ECP), tryptase, and calprotectin. The intestinal permeability was assessed by determining the 5-hour urinary excretion of [51Cr]EDTA. Calprotectin was also analyzed in native faecal samples. RESULTS: The ECP concentration in gut lavage fluid was significantly higher in the patients than in the controls (p = 0.007), but the overlap between groups was large. Food hypersensitivity was confirmed by positive DBPCFC in only 4 patients. On average, histamine and ECP concentrations were high in these patients. Tryptase, intestinal permeability, and faecal and lavage calprotectin levels were normal. CONCLUSIONS: Very few patients had objective evidence of food hypersensitivity. Analyzing intestinal permeability and inflammation markers in gut lavage fluid did not contribute to the diagnosis, but further studies on histamine and ECP are warranted.

Quality of life in patients with subjective food hypersensitivity: applicability of the 10-item short form of the Nepean Dyspepsia Index.

The aim of this study was to investigate quality of life and applicability of the 10-item short form of the Nepean Dyspepsia Index (SF-NDI) in patients with subjective food hypersensitivity. Fifty-two adult patients and 120 controls were examined using three questionnaires: Quality of life Nepean Dyspepsia Index (NDI), Gastrointestinal Symptom Rating Scale (GSRS), and Ulcer Esophagitis Subjective Symptoms Scale (UESS). To document psychometric properties, 20 of the patients filled in the SF-NDI questionnaire once more 4 weeks later. Patients had poor quality of life compared with controls from health care workers or general population (P < 0.001). Scores on SF-NDI were significantly correlated with scores on the GSRS (r = 0.34, P = 0.02) and UESS (r = 0.41, P = 0.003). The SF-NDI performed very satisfactorily, with a high reliability, construct validity, and responsiveness. Patients with subjective food hypersensitivity have considerably reduced quality of life. The SF-NDI provides reliable, responsive, and clinically valid measures of quality of life in these patients.

Food allergy and intolerance: response to intestinal provocation monitored by endosonography.

OBJECTIVE: Objective assessment of adverse reactions to food is a long-felt want. We report our preliminary experience with a new endosonographic allergen provocation test. METHODS: Twenty patients were examined, seven patients having food allergy and 13 having food intolerance. The duodenal mucosa was challenged with allergen extracts via a nasoduodenal tube. The responses were recorded using a miniprobe for endosonography through the tube. Thereafter, intestinal lavage was performed by giving 2 l PEG solution containing micro Ci (51)CrEDTA. The gut lavage fluid and urine for 5 h were collected. RESULTS: Increased mucosal thickness in response to provocation was recorded in 11 patients, but not more often or pronounced in the allergic than in the intolerance group. Interestingly, increased mucosal thickness associated with a new echogenic layer was seen in two patients and a sustained duodenal contraction, lasting 15-20 min associated with pain, in another two. Intestinal permeability and inflammatory mediators were not significantly different in the two groups. CONCLUSION: In patients with self-reported adverse reactions to food abnormal responses to duodenal provocation may be recognised by endosonography. However, neither endosonography nor intestinal permeability or faecal calprotectin responses were able to distinguish between food allergy and intolerance. Sustained duodenal contractions in response to food might be a cause of abdominal pain.

Effects of duodenal seal oil administration in patients with inflammatory bowel disease.

Long-chain n-3 PUFA in fish oil have modulating effects on inflammatory responses. The aim of this open pilot study was to investigate whether duodenal seal oil administration would benefit patients with inflammatory bowel disease (IBD). Seal oil (10 mL) was administered three times a day directly into the distal part of the duodenum via a nasoduodenal feeding tube for 10 d in 10 patients, 5 of whom had Crohn's disease and 5 ulcerative colitis. Nine of the 10 patients suffered from IBD-associated joint pain. Various parameters of disease activity and FA incorporation in tissues were analyzed before and after treatment. Following seal oil therapy, joint pain index, disease activity, and serum cholesterol level were significantly decreased, whereas the n-3 to n-6 ratio both in intestinal biopsies and blood was significantly increased. Measures of calprotectin concentration in gut lavage fluid, intestinal permeability, and lipid peroxidation were not significantly changed. The results suggest positive effects of seal oil in patients with IBD, especially on IBD-associated joint pain. Further controlled studies are warranted.