Risk of infection in patients with hidradenitis suppurativa on biologics or other immunomodulators: a systematic review and meta-analysis

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients’ quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86–1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.     

Participant experiences in a feasibility trial of supervised exercise training in adults with venous leg ulcers: A qualitative study

Exercise training can improve lower‐limb cutaneous microvascular reactivity in adults with venous leg ulceration; however, there is a lack of research on patients' views about the acceptability and feasibility of exercise interventions. The aim of this study was to explore participants' experiences of the trial “Exploring the Feasibility of Implementing a Supervised Exercise Training and Compression Hosiery Intervention in Patients with Venous Ulceration” (FISCU). Semi‐structured face‐to‐face and telephone interviews were used to investigate participants' experiences (n = 16) of taking part in the FISCU trial. Data were analysed using thematic analysis. Three overarching themes were identified, along with 11 sub‐themes: (a) sedentary cautious living (because of pain and reduced mobility, treatment and perceived control, and advice to rest and be careful), (b) key components of the exercise trial (including motivation, an individualised intervention supervised by a specialist exercise professional, and satisfaction with the intervention), and (c) benefits of exercise (physical benefits and healing, psychological well‐being, positive impact on comorbidities, and an improved self‐management strategy). This study found that an exercise intervention was viewed by participants as positive, acceptable, and feasible while living with a venous leg ulcer. An individualised and supervised exercise programme was key to build confidence to exercise.     

Risk factors and predictors of mortality of candidaemia among critically ill patients: role of antifungal prophylaxis in its development and in selection of non-<Emphasis Type="Italic">albicans</Emphasis> species

Purpose

The aim of the present study is to identify risk factors for development and predictors of mortality of candidaemia among critically ill patients.

Methods

A 1:7 case–control study was conducted during a 4-year period (2012–2015) in a Greek Intensive Care Unit (ICU). Candidaemia was confirmed by positive blood cultures. All yeasts were identified using API 20C AUX System or Vitek 2 Advanced Expert System. Epidemiologic data were collected from the ICU computerized database and patients’ chart reviews.

Results

Fifty-three patients developed candidaemia with non-albicans species being the predominant ones (33 patients, 62.3%). Multivariate analysis found that prior emergency surgery, malignancy, hospitalization during summer months, prior septic shock by KPC-producing Klebsiella pneumoniae and number of antibiotics administered were independently associated with candidaemia, while, prior administration of azole was a protective factor. Non-albicans candidaemia was associated with number of antibiotics administered and prior administration of echinocandin. Mortality of 14 days was 28.3% (15 patients) and was associated with SOFA score upon infection onset and septic shock, while, appropriate empirical antifungal treatment was associated with better survival.

Conclusions

Prophylactic azole administration prevents development of candidaemia, while, echinocandin administration predisposes to non-albicans candidaemia. Empirical administration of an appropriate antifungal agent is associated with better survival.

     

Patients with gastroesophageal reflux disease and respiratory manifestations do not present lung function disorders during cardiopulmonary exercise test

Gastroesophageal reflux disease (GERD) has been associated with a variety of pulmonary manifestations, but it is unclear if gastroesophageal reflux causes any abnormality in pulmonary function. Cardiopulmonary exercise test (CPET) is a specialized method that is used to evaluate respiratory function during exercise. The aim of this study was to reveal any abnormality of pulmonary function in patients with GERD and respiratory symptoms. We evaluated 34 patients with GERD (24 men and 10 women, aged 21–63) and extraesophageal respiratory symptoms (wheezing and/or cough) before therapy and after a 12‐week treatment with double dose of omeprazole. No patient presented abnormal spirometry. CPET was performed in all the patients at baseline and after completion of the 12‐week treatment. CPET parameters including VO₂rest, VO₂max, VCO₂rest, VCO₂max, O₂–puls rest, O₂–puls max, HR (heart rate) rest, HRmax, PETCO₂rest, PETCO₂max, and VE/VCO₂ slope were recorded pretreatment and posttreatment. Twenty‐four patients (70.6%) had esophagitis (grade A–D), 16 patients had hiatal hernia (47.1%), and 13 patients (38.2%) tested positive for Helicobacter pylori. All of the patients completed the CPET. No one presented shortness of breath or respiratory symptoms. CPET parameters were within normal limits in all of the patients. Twenty‐eight patients were reevaluated. No improvement in any CPET parameter posttreatment was observed despite remission of esophageal and extraesophageal respiratory symptoms in all patients. No statistically significant difference was observed pretreatment and posttreatment between the patients older and younger than 40 years, smokers and nonsmokers, Hp(+) and Hp(–) patients, and those with and without hiatal hernia and esophagitis. The patients with GERD and respiratory manifestations and normal spirometry present no pulmonary dysfunction during CPET. No alterations in CPET values posttreatment or differences in CPET values according to age, smoking, Hp status, presence of esophagitis, or hiatal hernia were observed.     

Chemotherapy with gemcitabine, cisplatin, and docetaxel in the treatment for patients with muscle-invasive bladder cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG)

Purpose

To assess the antitumor activity and toxicity of gemcitabine, cisplatin, and docetaxel (GCD) regimen in patients with locally advanced or metastatic urothelial cancer.

Patient and methods

Chemotherapy-na?ve patients, aged ??70?years with measurable or evaluable disease and a performance status (PS) of 0?C2 were treated with sequential cisplatin 80?mg/m² (d1), gemcitabine 1,100?mg/m² (d1 and d14), and docetaxel 80?mg/m² (d14) every 28?days.

Results

Sixty patients with an ECOG PS of 0?C2 were enroled. Most (71.7%) patients had stage IV disease. A median number of 4 chemotherapy cycles per patient (range, 1?C9) was administered. Eight (13.3%) patients achieved a CR and 16 (26.7%) a partial response (PR) (intention-to-treat: ORR 40%; 95% CI 27.6?C52.4%). Thirteen (21.7%) and 23 (38.3%) patients experienced stable and progressive disease, respectively. The median time to progression (TTP) was 7.7?months (range, 0.7?C43.4), and the median overall survival 21.4?months (range, 0.7?C68.6). Grade 3 and 4 neutropenia occurred in 27 (45%) patients and grade 3 and 4 thrombocytopenia in five (8.3%). Three (5%) patients developed febrile neutropenia. There were no treatment-related deaths. Severe non-haematological toxicity was infrequent.

Conclusions

The GCD combination is an active and well-tolerated regimen in patients with chemotherapy-naive locally advanced or metastatic TCC and merits to be further investigated.     

P. gingivalis and E. coli lipopolysaccharides exhibit different systemic but similar local induction of inflammatory markers

BACKGROUND: Porphyromonas gingivalis is a Gram-negative bacterium that is an important etiologic agent of human adult periodontitis. The goal of the study was to test the hypothesis that two isoforms of P. gingivalis lipopolysaccharide (PgLPS), PgLPS(1435)(/1449) and PgLPS(1690), exhibit differences in their capacity to stimulate systemic versus local responses compared to Escherichia coli lipopolysaccharide (LPS). METHODS: LPS was inoculated into the scalp of mice, and the response was measured locally at the site of inoculation and systemically in the heart/aorta. Vascular cell adhesion molecule (VCAM)-1 was assessed at the protein level by enzyme-linked immunosorbent assay, and VCAM-1, E-selectin, and intercellular adhesion molecule (ICAM)-1 were assessed at the RNA level of the RNase protection assay. Serum tumor necrosis factor-alpha (TNF-alpha) levels were also measured. RESULTS: E. coli LPS and both isoforms of P. gingivalis LPS were relatively potent in stimulating the expression of inflammatory markers, with E. coli LPS being more potent. In contrast, when the systemic response was measured in the heart/aorta, E. coli LPS, but not P. gingivalis LPS, significantly induced inflammatory markers. At moderate to low doses (1 and 10 microg per injection), serum TNF-alpha levels were minimally induced by P. gingivalis LPS compared to E. coli LPS. CONCLUSIONS: Both forms of P. gingivalis LPS stimulated an inflammatory response when injected into connective tissue but were minimally stimulatory when a systemic response was measured. In contrast, E. coli LPS was a potent stimulus at the systemic and local levels.     

Prevalence of chronic diseases and morbidity in primary health care in central Greece: An epidemiological study

Background  

In Greece there is lack of large epidemiological studies regarding morbidity and mortality in primary health care. The aim of the present study was to estimate the prevalence and morbidity of the most common diseases in a large population sample from primary health care.