Halogen, Chalcogen, Pnictogen, and Tetrel Bonding in Non-Covalent Organocatalysis: An Update.

The use of noncovalent interactions based on electrophilic halogen, chalcogen, pnictogen, or tetrel centers in organocatalysis has gained noticeable attention. Herein, we provide an overview on the most important developments in the last years with a clear focus on experimental studies and on catalysts which act via such non-transient interactions.

European Respiratory Society guideline on various aspects of quality in lung cancer care.

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.

Experiences from integrating water and sanitation safety planning in small systems in rural Serbia.

The WHO recommends a risk management approach to ensure safe drinking-water and sanitation, so-called Water Safety Planning and Sanitation Safety Planning. However, applying these risk management approaches separately in small-scale drinking-water supply and sanitation systems might be challenging for rural communities with limited human, financial, and administrative resources. An integrated approach seems a better option. In this study, an integrated water and sanitation safety planning (iWSSP) approach was developed together with guidance and training material for the practical application of this novel approach. The integrated approach was piloted in three small systems in rural Serbia to identify benefits and suggestions for improvement which can be used for potential future scaling-up. Implementing iWSSP at the pilot sites contributed to a better understanding of both drinking-water supply and sanitation systems. It also resulted in increased awareness, knowledge, and understanding among staff of drinking-water supply and sanitation services. Key experts, including external facilitators, played a crucial role in the implementation of iWSSP. Future scaling-up of the integrated approach could be enabled if more guidance, easy-to-use training materials and templates become available which can be adapted and updated as needed.

Correlation of Short Leukocyte Telomeres and Oxidative Stress with the Presence and Severity of Lung Cancer Explored by Principal Component Analysis.

Lung cancer (LC) is the second most common malignancy and leading cause of cancer death. The potential "culprit" for local and systemic telomere shortening in LC patients is oxidative stress. We investigated the correlation between the peripheral blood leukocyte (PBL) telomere length (TL) and the presence/severity of LC and oxidative stress, and its usefulness as LC diagnostic marker. PBL TL was measured in 89 LC patients and 83 healthy subjects using the modified Cawthon RTq-PCR method. The relative PBL TL, found to be a potential diagnostic marker for LC with very good accuracy (P < 0.001), was significantly shorter in patients compared to the control group (CG) (P < 0.001). Significantly shorter telomeres were found in patients with LC TNM stage IV than in patients with stages I-III (P = 0.014), in patients without therapy compared to those on therapy (P = 0.008), and in patients with partial response and stable/progressive disease compared to those with complete response (P = 0.039). The total oxidant status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB) and C-reactive protein (CRP) were significantly higher in patients compared to CG (P < 0.001) and correlated negatively with TL in both patients and CG (P < 0.001). PCA showed a relation between PAB and TL, and between the EGFR status and TL. Oxidative stress and PBL telomere shortening are probably associated with LC development and progression.

Comorbidity burden and survival in patients with idiopathic pulmonary fibrosis: the EMPIRE registry study.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry. METHODS: For this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient's past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan-Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment. RESULTS: A population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths. CONCLUSIONS: The majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.

Water, sanitation, and hygiene services in health care facilities in the Autonomous Province of Vojvodina, Serbia.

Provision of safe water, sanitation, and hygiene (WASH) services in health care facilities is a priority at the global, national, and local levels. To inform improvements planning, conditions of WASH, waste management, and environmental cleaning were assessed in 81 facilities in the Autonomous Province of Vojvodina, Serbia, as part of a nationally representative survey in 2019. The survey included on-site checks, structured interviews, and drinking-water quality analysis. WHO/UNICEF indicators for WASH service levels and an advanced service level defined at the national level were applied. The results showed that all investigated facilities provided basic water services; 94% of facilities provided basic hygiene and waste management services; 58 and 2%, respectively, provided basic cleaning and sanitation services. Only 1% of investigated facilities met the basic level for all five WASH dimensions. Advanced service levels were only met for hygiene, waste management, and/or cleaning in 15-38% of facilities. In 33% of health care facilities, drinking-water quality was not in compliance with the national standards. The results revealed that there is a need for increased awareness and efforts to ensure basic provisions for sanitation, environmental cleaning, and drinking-water safety.

TENS Improves Cisplatin-Induced Neuropathy in Lung Cancer Patients.

Background: Cisplatin-induced peripheral neuropathy is a common complication of cisplatin therapy, which develops in most patients with lung cancer. There are no effective preventive measures and once it occurs there is no effective therapy, except symptomatic. In this study, we aimed to assess the effect of transcutaneous electrical nerve stimulation (TENS) therapy on the pain intensity and the quality of life of patients with cisplatin-induced neuropathy. Material and Methods: A prospective cohort study was performed from 2013 to 2018, at the Clinical Center of Serbia. After the initial evaluation of 106 newly diagnosed patients with lung cancer, 68 patients did not have peripheral neuropathy. These 68 patients continued in the study and started the cisplatin chemotherapy. Forty of these patients developed cisplatin-induced neuropathy, which was manifested by neuropathic symptoms and proven by ENG examination. All patients with cisplatin-induced neuropathy were treated with TENS therapy. Their neuropathic pain and quality of life were evaluated using the following questionnaires at diagnosis, after cisplatin therapy and after four weeks of TENS use: DN4, VAS scale, EORTC QLQ-C30 and FACT-L. Results: Two thirds (68%) of the patients with cisplatin-induced neuropathy were male and the majority were smokers (70%). Adenocarcinoma was the most common (38%), followed by squamous (33%) and small-cell carcinoma (28%). The application of TENS therapy had a positive effect on reducing the neuropathic pain and increasing the quality of life for patients with painful cisplatin-induced neuropathy. The VAS and DN4 scores significantly decreased after TENS therapy, in comparison to its values after cisplatin therapy (p < 0.001). After TENS therapy, patients had significantly higher values in most of the domains of EORTC QLQ-C30 and FACT- L, in comparison with the values after cisplatin therapy (p < 0.001). Conclusion: The application of TENS therapy has a positive effect on reducing neuropathic pain and increasing the quality of life for patients with lung cancer and cisplatin-induced neuropathy.

UNUSUAL CLINICAL COURSE OF NEUROSARCOIDOSIS MANIFESTED WITH ACUTE HYDROCEPHALUS.

Approximately 5% to 15% of patients with systemic sarcoidosis develop neurological complications. However, the actual prevalence of subclinical disease may be higher. Symptoms are not specific, and may resemble those of other neurological diseases. Hydrocephalus occurs in 6% of patients with neurosarcoidosis. Acute hydrocephalus is extremely rare and when it occurs, it is usually difficult to diagnose, thus leading to possible complications. We present a patient who developed acute hydrocephalus due to neurosarcoidosis, for which he had to be operated on; soon after the operation, cranial infection developed that required definitive drainage system and ventriculoperitoneal shunt had to be implanted. In further complicated clinical course, after four years on corticosteroid therapy (corticosteroid dependent sarcoidosis), he had to be urgently operated on because of significant ventricular catheter adhesions, but several days after the operation he died in coma because of progressive brain edema not responding to treatment. As hydrocephalus due to neurosarcoidosis has high morbidity and mortality, early diagnosis and proper treatment are of utmost importance.

Access to Novel Drugs for Non-Small Cell Lung Cancer in Central and Southeastern Europe: A Central European Cooperative Oncology Group Analysis.

BACKGROUND: Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries. MATERIAL AND METHODS: The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries. RESULTS: Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies-even for ALK inhibitors and checkpoint inhibitors in first-line-there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries. CONCLUSION: The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making.

The European MultiPartner IPF registry (EMPIRE): validating long-term prognostic factors in idiopathic pulmonary fibrosis.

BACKGROUND: Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF. METHODS: The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors. RESULTS: The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9). CONCLUSIONS: EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.