The Association Between Hidradenitis Suppurativa and Diet: An Update.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful inflammatory lesions, predominantly affecting areas of the skin rich in apocrine glands, such as inguinal, axillary, submammary, and anogenital regions, with an estimated global prevalence between 1%-4%. The treatment of HS is challenging with various treatment modalities employed to control the disease. Since the condition is chronic and life-impairing, many patients have looked for ways to complement their conventional treatment procedures with non-medical interventions, among which dietary interventions have been of particular interest. Researchers have looked for ways to connect the gastrointestinal system with the skin through the ˝skin-gut axis concept˝ introducing a strong association between the microbiome of the gastrointestinal system and the skin. In addition, diet stimulation of insulin and IGF-1 (insulin-like growth factor 1) may impact signaling pathways playing a role in HS pathogenesis. Patients have tried various dietary interventions to alleviate their symptoms of inflammation and suppuration. Among the different dietary approaches that have been described are paleo, autoimmune, Mediterranean, and elimination diet regimes. Dietary supplements have become the mainstay of lifestyle factors aimed at improving the clinical signs and symptoms of HS. This review aims to synthesize and present the current findings on diet as a modifiable factor in HS, helping the patients to navigate through the data and helping them make informed choices on their healthy lifestyles.

Rituximab - Progress but Still Not a Final Resolution for Pemphigus Patients: Clinical Report From a Single Center Study.

Pemphigus is a rare autoimmune disease characterized by the production of pathogenic autoantibodies against desmosomal adhesion proteins, desmoglein 1 and 3. The pathophysiological process leads to the development of blisters and erosions on mucosal and/or skin surfaces as the main clinical manifestation of the disease. Rituximab emerged as the first-line therapeutic option for pemphigus due to its ability to induce remission by depleting peripheral B lymphocytes. Our aim was to assess the efficacy of rituximab in the treatment of patients in Croatia. A single-center, retrospective study was conducted on 19 patients treated with rituximab following a rheumatoid arthritis dosing protocol between October 2015 and March 2021, with a mean follow-up of 24.1 months. After the first rituximab cycle, two patients achieved complete remission off therapy (10.5%), and six patients achieved complete remission on minimal therapy (31.6%). Partial remission was observed among ten patients (52.6%). Eight patients (44.4%) relapsed after the first rituximab cycle. The mean relapse time was 21 months. Seven patients received two rituximab cycles, and three patients received three cycles. Overall, 13 out of 19 patients experienced complete remission at some point during the study, while there were no non-responders after the rituximab treatment. No statistically significant associations were observed between age, sex, type of disease involvement and clinical remission, either on or off therapy. A steady decrease in anti-desmoglein 1 and anti-desmoglein 3 levels was measured among all patients following rituximab treatment. One patient experienced a treatment-related adverse event of infectious etiology (cellulitis). One patient died following the first rituximab cycle, with the cause of death likely not to be associated with the treatment. Rituximab is an effective disease-modifying agent in the treatment of pemphigus with the main benefit of reducing corticosteroid exposure and steroid-related side effects among pemphigus patients. However, a feature of rituximab therapy is high relapse rates and the need for repeated treatment cycles to achieve complete remission. Developing an optimal protocol for rituximab treatment and finding suitable markers for predicting relapse will improve the management of pemphigus patients.

Pemphigus-The Crux of Clinics, Research, and Treatment during the COVID-19 Pandemic.

Pemphigus is a rare autoimmune disease characterised by the production of pathogenic autoantibodies in response to different desmosome proteins. The pathophysiological process leads to the development of blisters and erosions on mucosal and/or skin surfaces. The classical clinical variants of pemphigus are pemphigus vulgaris and pemphigus foliaceus. A diagnostic delay is very common in pemphigus, especially among patients with mucosal involvement. However, in recent years we have witnessed considerably fewer patients with extensive mucocutaneous manifestations, since patients with oral lesions are referred to dermatologists to start the treatment much sooner than they had been previously. Among non-classical variants of pemphigus, unusual cases with discrepancies between autoantibody profiles and clinics challenge the "desmoglein compensation theory". The identification of several other autoantigens that perform a role in the pathogenesis of different variants of pemphigus will progress immunodermatology towards an approach that will determine personalized pemphigus subtypes for each patient. Comorbidities among patients are primarily associated with the prolonged use of corticosteroids and other immunosuppressive agents. The SARS-CoV-2 pandemic raised concerns regarding the immunosuppressive effects of treatment and the risk of a more complicated COVID-19 infection, as well as on the ability to develop an adequate vaccine response.

Understanding the Relationship Between Smoking and Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disease affecting hair follicles in intertriginous areas, characterized by deep, recurrent, painful nodules and abscesses, fistulae, sinus tracts, and scarring. With a prevalence of 1-4%, HS is not an uncommon disease. Several risk factors have been linked with the development of HS, such as genetic predisposition, smoking, and obesity, leading to the hypothesis that HS develops as a result of environmental triggers in a genetically susceptible individual. Smoking has been recognized as one of the environmental factors with the most impact on HS. This review aims to provide a comprehensive and holistic view on how smoking habits affect the incidence, severity, treatment, and pathophysiology of HS. A growing body of published literature has reported the association between smoking and HS, despite limitations in proving the causal relationship due to the retrospective design of the available studies. There is a consensus that patients with HS who are active smokers have a higher number of affected body areas than patients with HS who do not smoke or have stopped smoking. Similarly, it is recommended for patients with HS to discontinue tobacco use because of its association with weaker treatment response. Studies on the pathophysiological mechanism of smoking on the skin show that tobacco smoke with many of its chemicals as well as nicotine promote the proinflammatory cytokines found in HS lesions, activate the nicotinic acetylcholine (nAChRs) and aryl hydrocarbon receptors (AHRs), and further suppress Notch signaling pathway.

Impatience of health professions students for health equity--can a new definition help?

The International Federation of Medical Students' Associations (IFMSA) is concerned that students are not graduating feeling energized by their social purpose. IFMSA raises a question about the role of the definition of health in limiting the comprehensiveness of the current approach to health and health care in medical and health professions education. IFMSA surveyed medical students about medical curricula. We found that a minority of surveyed students have experienced interdisciplinary teaching, with the lowest exposure in low- and middle-income countries. Medical students are clearly stating their dissatisfaction with the lack of holistic and comprehensive approach to health and health care. Our impatience for contributing to health equity is a virtue in seeking change in curricula and broader collaboration for health.

Do medical students want to learn about global health?

BACKGROUND: One objective of the United Nations Global Strategy for Women's and Children's Health relates to ensuring a sufficiently skilled workforce. To prepare future healthcare professionals for their role in the 21st century as members of this workforce, awareness of global health is essential, but few studies have explored student perspectives on such education. The main objectives of this study were to establish the views of medical students on learning about women's and children's health in low-income countries, to identify the nature and extent of learning already experienced, and to assess the demand for such learning. DESIGN: A questionnaire survey was conducted at three meetings of the International Federation of Medical Students Associations (IFMSA). Questionnaires were distributed to 500 participants from 75 countries and 336 medical schools, and 492 usable questionnaires were returned. Data were analysed using SPSS Version 20 and statistical analysis was undertaken using Fisher's exact test. RESULTS: There were 492 questionnaires included in the analysis. Forty-eight per cent of participants were from low-middle income countries and 52% were from high-income countries. Less than half (43%) of the respondents had received some teaching on women's and children's health in low-income countries. Teaching received was primarily (96%) through lectures in the second year of study. Ninety-one per cent of respondents thought such teaching would be important and stated that group work (66%) would be the preferred method. In total, only 14% thought they had received sufficient teaching on global health and on women's and children's health in low-income countries. CONCLUSIONS: This study has revealed a high demand among medical students for global health teaching, particularly on women's and children's health in low-income countries. The timing and methods of existing teaching on these topics does not match that desired by medical students. To help address this gap, a collaborative approach is proposed which includes students' views in the processes for revitalising medical curricula to meet the needs of the 21st century.

Bronchoalveolar pH and inflammatory biomarkers in newly diagnosed IPF and GERD patients: a case-control study.

BACKGROUND: Several studies have suggested that idiopathic pulmonary fibrosis (IPF) may be related to repeated aspiration of gastric contents over long periods of time. We aimed to investigate differences between pH measured directly in the lung, and biomarkers of acute inflammation in patients with newly diagnosed IPF and in patients with newly diagnosed GERD. MATERIAL AND METHODS: All subjects (N=61) underwent collection of medical history, physical examination, pulmonary function testing, bronchoscopy, endoscopy, arterial blood gas analyses, and biochemical testing. RESULTS: Previously diagnosed GERD was found in 56.7%, typical symptoms of reflux in 80%, and Helicobacter pylori in gastric biopsy specimens in 76.6% of the cases. pH in peripheral branches of bronchi in the cases was 5.32 ± 0.44 and was 6.27 ± 0.31 (p<0.001) in the control group. The average values of LDH, ALP, and CRP in bronchoalveolar aspirate and in serum, as well as TNF-alpha in bronchoalveolar aspirate, were significantly higher in IPF patients. CONCLUSIONS: The more acidic environment in the bronchoalveolar aspirate of the IPF subjects could contribute to the development or progression of IPF, possibly via changes in local metabolism or by damaging local cells and tissue. However, further studies with larger numbers of patients are required to clarify the role of gastric fluid aspiration in IPF pathogenesis. Our preliminary work has identified inflammatory biomarkers LDH, ALP, and TNF-alpha as potentially important in the pathologic processes in IPF. Further research is needed to determine their importance in clinical intervention and patient care.

Undiagnosed AIDS in patients with progressive dyspnoea: an occupational risk for healthcare workers in Croatia.

Pulmonary diseases are well documented and diverse in many patients with HIV in clinical stages 3 and 4. It is not unusual that these patients, most of whom do not know that they are already HIV-infected, are first examined and hospitalised by respiratory medicine specialists. While HIV-infection is relatively simple to diagnose if accompanied by advanced clinical manifestations and is regularly checked in patients with increased risk, this is not the case in low-risk patients, particularly in countries with low-level HIV epidemic and therefore low index of suspicion. Regular examination involves a series of tests, often including bronchoscopy with transbronchal lung biopsy in order to identify an interstitial lung disease and/or progressive dyspnoea. It is not uncommon that patients provide false or incomplete information about their lifestyle, which can mislead the clinician. At this point, HIV-infection is usually not suspected and healthcare workers may not strictly be following the safety principles which are otherwise applied when HIV-infection is known or suspect, although universal precautions are routine practice. At this point, the risk of exposure is the highest and HIV-transmission to healthcare workers is the most likely to occur. The cases presented here indicate that patients with progressive dyspnoea, which is typical of interstitial lung diseases, should undergo HIV-testing as a part of good clinical practice, even in a country with low-level HIV epidemic.

Combined inhibition of PI3K and mTOR exerts synergistic antiproliferative effect, but diminishes differentiative properties of rapamycin in acute myeloid leukemia cells.

A novel strategy has been suggested to enhance rapamycin-based cancer therapy through combining mammalian target of rapamycin (mTOR)-inhibitors with an inhibitor of the phosphatydilinositol 3-kinase PI3K/Akt or mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. However, recent study demonstrated the potentiating effect of rapamycin on all-trans-retinoic acid (ATRA)-mediated differentiation of acute myelogenous leukemia (AML) cells, prompting us to investigate the effects of longitudinal inhibition of PI3K/Akt/mTOR signaling pathway on both proliferation and differentiative capacity of AML. In NB4, HL-60, U937 and K562 cell lines, rapamycin exerted minimal antiproliferative effects, and combining PI3K inhibitor LY 294002 and rapamycin inhibited proliferation more than LY 294002 alone. Rapamycin potentiated differentiation of ATRA-treated NB4 cells, but the combination of rapamycin and LY 294002 inhibited the expression of CD11b in both ATRA- and phorbol myristate acetate (PMA)-stimulated cells more than PI3K inhibitor alone. These results demonstrate that, although the combination of PI3K inhibitor and rapamycin is more effective in inhibiting proliferation of AML, the concomitant inhibition of PI3K and mTOR by LY 294002 and rapamycin has more inhibitory effects on ATRA-mediated differentiation than the presence of PI3K-inhibitor alone, and diminishes positive effects of rapamycin on leukemia cell differentiation.

Increasing of malignant pleural mesothelioma: burning issue in Split-Dalmatian County, Croatia.

Asbestos-related diseases are one of the burning public health issues worldwide. The incidence and the epidemiological patterns of malignant pleural mesothelioma in Split-Dalmatian County, where a large part of Croatian industry related to asbestos processing and use have been situated were assessed in this study. The history of asbestos-related issues and development of current legislation in Croatia was also discussed briefly. Data on the incidence were collected retrospectively from the medical records of patients with malignant pleural mesothelioma treated at Department of Pulmonary Diseases University Hospital Split during the 2000-2007 period. A total of 137 new cases was recorded with the mean incidence of 3.55/100,000 and the trend was increasing over years compared with 1992-1995 period in the same county when the mean incidence was 1.7/100,000. Men accounted for 85.4% of all cases. The mean age of patients was 64.9 +/- 15.4 years. The majority of patients were occupationally exposed to asbestos (85.4%), 8.8% had environmental exposure, and 2.2% had domestic exposure. The type of household exposition was in 5.8% of patients. More than half of the cases were exposed to asbestos 31-40 years. The mean length of exposure was 28.87 +/- 15.63 years. The incidence of malignant pleural mesothelioma in Split-Dalmatian County has been obviously increasing due to the predominantly occupational exposure and it is reasonable to assume that it will remain high in the next two-three decades and to be a reason for concern and fear among the general population.