Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator involve in inflammatory signaling/s associated with the development of respiratory disorders, including inflammatory disease and cancer, although many doubts about the precise mechanism are still to be clarified. In this study we aim to investigate the role of S1P, highly released from epithelial lung cancer cells, in circulating cellsmediated inflammatory processes. We used peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers and lung cancer patients to discriminate between the physiological and pathological role of S1P. We found that S1P exacerbates the pro-inflammatory milieu by inducing the release of TNF-α and IL-6 from lung cancer-, but not healthy-derived PBMCs in a S1P receptor 3 (S1PR3)-dependent manner. The pharmacological blockade of ceramidase and sphingosine kinases (SPHKs), key enzymes of S1P metabolism, in lung cancer-derived PBMCs completely reduced the release of both TNF-α and IL-6 after exogenous S1P stimulation. Furthermore, S1P-induced IL-6 release from PBMCs of lung cancer patients was mTOR- and K-Ras-, but not NF-κB-dependent. Interesting male adenocarcinoma and female squamous patients were more susceptible to S1P that induced IL-6-dependent inflammation. These data exalt S1P as one of the main orchestrators of lung cancer-associated inflammatory pathways, shedding light on a new pro-inflammatory mechanism mediated by immune circulating cells which sees S1P/IL-6 axis as a keystone in a complex landscape such as lung cancer.

Background. SARS-CoV-2 has caused a world-wide pandemic inducing a disease known as coronavirus disease 19 COVID-19, which may be associated to pulmonary fibrosis. A significant number of COVID-19 patients, although negative to the oral-pharyngeal swab, experience prolonged symptoms, herein called post COVID-19 (PC).
Aims and objectives. Based on the fact that the mechanism/s underlying SARS-CoV-2-derived pulmonary fibrosis are still not well defined, the aim of this study was to identify blood biomarkers to predict lung fibrosis-like changes in PC patients
Methods. We used blood samples collected from healthy subjects, anti-SARS-CoV-2 vaccinated (VAX) subjects, and PC patients who were stratified according to the severity of the disease and chest computed tomography (CT) scan data.
Results. We found that C reactive protein (CRP), complement complex C5b-9 and LDH, but not IL-6, were still higher in PC patients, independent of the severity of the disease and lung fibrotic areas. Interestingly, fibrotic PC were characterized by higher plasma levels of IL-1α, CXCL-10, TGF-β, but not of IFN-β, compared to healthy and VAX groups. In particular, 19 out of 23 (82.6%) severe PC and 8 out of 29 (27.6%) moderate PC patients presented signs of lung fibrosis, associated to lower levels of IFN-β, but higher IL-1α and TGF-β.
Conclusions. Our data suggest that higher IL-1α and TGF-β, and lower plasma levels of IFN-β could predict an increased relative risk (RR = 2.8) of lung fibrosis-like changes in PC patients.

In this topic we will discuss the  use of new antibiotics and new suggestions from these in term on patient’s outcomes in hospital-acquired pneumonia(HAP).
HAP is simply a pneumonia that occurs 48 hours or greater after hospital admission and the symptoms of pneumonia are not present at the time of admission or within those first 48 hours of hospital admission. The next most common category is ventilator-associated pneumonia or VAP and this is a pneumonia arises 48 hours after implementation of mechanical ventilation. There is  also a category of ventilated HAP or VHAP,which  is a pneumonia that occurs 48 hours  after admission.Again,the patient does not have symptoms of pneumonia within those first 48 hours and is not associated with mechanical ventilation.However,this type of pneumonia is fulminant and after patients develop symptoms ,they often require emergent intubation and mechanical ventilation.
Hospital-acquired bacterial pneumonia (HABP) is one of most common nosocomial infections in critically ill patients and is a major cause of mortality. Up to about 25%of all ICU infections and more than half of antibiotics prescribed in critical care units, are associated with pneumonia. Mortality rates are actually quite high as well, ranging  from about  20% to 50%.Often the most fulminant serious type of pneumonia in the ICU is this ventilated HABP, followed by ventilator –associated bacterial pneumonia, and finally our lowest mortality rates in non-ventilated hospital HABP.
A major risk factor for pneumonia in the ICU is mechanical ventilation; about 10% in patients who are intubated may develop ventilator-associated bacterial pneumonia. Ventilator-associated bacterial pneumonia is associated with significant bad outcomes in not only increased mortality ,but also increased duration of ICU stay and overall hospital stay .Late onset pneumonia, particularly in the ICU, is associated with an increased risk for multidrug –resistant organisms. The top pathogens implicated in hospital-acquired pneumonia are represented generally by Staphylococcus aureus ,especially MRSA,but also by gram-negatives:Pseudomonas ,Acinotebacter,Eschericia coli,and Klebsiella ,particularly ESBL-producing and extensively drug-resistent Enterobacteriaceae.The incidence of hospital-acquired pneumonia caused by multi-drug-resistant pathogens id increasing worldwide. So, we are in front of problem-related to ESBL Enterobacterales and very important problems sustained by carbapenem-resistant Pseudomonas,Acinotebacte,Enerobacterales  as causative agents of HABP and VABP.
Cefiderocol is a novel siderophore cephalosporin, which means that it crosses the bacterial membrane using active ion transport channels, almost like a Trojan horse. It is very stable against all Ambler classes of beta-lactamases. including Metallo-beta-lactamases. And most importantly, it has very broad Gram-negative activity to Acinetobacter, Pseudomonas, CRE, even to Streptrophomonas. The CREDIBLE-CR study has been shown non-inferiority of cefiderocol compared to BAT(best available therapy) for nosocomial pneumonia. There was higher mortality, with cefiderocol primarily found in a subset of patients infected by Acinotebacter species, particularly during the early and the late period of study.
Another new antibiotic is imipenem –relebactam which has been compared to piperacillin-tazobactam and has shown a similar effect against Pseudomonas aeruginosa.
The REPROVE study demonstrated the effect of ceftazidime-tazobactam to endpoints of patients with VABP compared to meropenem and the ceftadizime at the end was non-inferior to meropenem across all the ednpoints.
Another trial is the ASPECT nosocomial one, nosocomial pneumonia, in which ceftolozane –tazobactam has been compared with meropenem and there were no differences in all-cause mortality at day 28  in patients with ventilated HAP.
Another question is related to the use of clinical scores and biomarkers in order to decrease the duration of the treatment, because for the majority of the infections and particularly for pneumonia,8, maximum  10 days is probably enough for managing these difficult-to-treat infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a life-threatening pneumonia caused by an enveloped, single-stranded RNA betacoronavirus belonging to the coronaviridae 2B lineage [1]. The SARS-CoV-2 genome is enclosed in the nucleocapsid protein, and is surrounded by three protective structural proteins, including membrane protein, envelop protein, and spike protein [5]. The structural proteins are potential targets for the development of antivirals, and vaccines for early treatment and prevention of the progression of Covid-19. Entry of SARS-CoV-2 into host cells is mediated by the spike glycoprotein [7,8], which is composed of two functional subunits, including the S1 and S2 subunits. The standard of care of severe Covid-19 include high-flow nasal oxygen, corticosteroids, remdesivir, and anti-interleukin-6, such as tocilizumab, or Janus kinase inhibitors, including baricitinib. However, mortality due to Covid-19 is prohibitively very high. Monoclonal antibodies which binds to epitopes on the receptor binding domain (RBD) of the spike protein of SARS-CoV-2, have the potential for early treatment of Covid-19, and in preventing progression of the disease. Bamlanivimab plus etesevimab [1-3], casirivimab plus imdevimab [4-6], and sotrovimab [7] are recombined human monoclonal antibodies that bind to different epitopes in the RBD of the spike protein. They have been shown to reduce the risk of hospitalization and death in about 70-85% of nonhospitalized patients who had mild to moderate Covid-19 symptoms [12,19-21]. Bamlanivimab-etesevimab, and casarivimab-imdevimab are still effective against Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants, but they have reduced susceptibility against the Omicron (B.1.1.529) variant of concern. Therefore, these spike protein entry inhibitors should not be recommended in countries where the Omicron variant of concern prevalence exceeds 80% [17]. Sotrovimab has been demonstrated to retain vitro and in vivo activity against all currently tested variants of concern and interest of the SARS-CoV-2 virus, including Delta (B.1.617), Delta Plus (AY.1 or AY.2), and Omicron (B.1.1.529) [13-15]. Sotrovimab is recommended for the treatment of nonhospitalized patients with mild to moderate Covid-19, and for post-exposure prophylaxis in countries severely affected by the Omicron variant [16].  Other recommended antivirals include remdesivir [22], nirmatrelvir plus ritonavir [23], and molnupiravir [24], which are active against the Omicron variant.
Conclusion & Significance: Treatment of nonhospitalized patients with Covid-19 is challenging because of the emergence of SARS-CoV-2 variants which become less susceptible to novel spike entry inhibitors.

Problem: Continuous personal monitoring is a benchmark for assessing exposure to air pollution. European air quality standards for particulate matter (PM) use the mass concentration of PM (PM with aerodynamic diameters ≤ 10 μm (PM10) or ≤2.5 μm (PM2.5)) as the metric. It would be desirable to understand if black carbon (BC) can be a better indicator than PM10 and PM2.5. To achieve this goal, it is necessary to implement social, environmental and clinical data by developing real-time laboratories on an urban scale. This research discusses an integrated approach on three pilot studies developed in the city of Turin (Italy). The activities involved the resident population and some volunteers with chronic obstructive pulmonary disease (COPD).
Methodology and Theoretical Orientation: The Living Lab developed in Turin was organized in three pilot studies (LLs). LL#1 involved 15 volunteer citizens residing in Turin who were observed and monitored for a week (November 2021). The BC concentrations detected with AE51 portable sensors were superimposed on the information collected by the urban monitoring network. LL#2 observed (October 2020-October 2021) the respiratory parameters of 50 male volunteers with mild COPD and residing in Turin in areas with different traffic densities. More precisely, 25 volunteers resided in high-traffic areas and 25 in low-traffic areas. LL#2 allowed us to investigate the associations between PM, BC and forced expiratory volume in the 1st second (FEV1). Finally, LL#3 developed a social survey on over 300 Turin citizens who participated in a semi-structured questionnaire on urban air quality and their behaviors adopted in favor of urban air quality. Each apparently different LLs is interconnected by a common denominator: the data collected by users, such as active human- sensors, provide information to be integrated in the management of air quality regulation policies at the local level. Results: A total of 8640 eBC measurements were obtained during LL#1 with an average daily personal exposure of 3.1 µg/m 3 (± SD 1.3). The change in movement patterns and the variability of microenvironments were determinants of exposure. LL#2 showed that high traffic density is significantly associated with lower forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC). LL #2 results highlight that people with persistent respiratory symptoms and residing in busier areas appear to be more vulnerable to BC exposure and have greater sleep wheezing.
Conclusion and Meaning: Preliminary results highlight the potential utility of Living Labs for innovative approaches to designing an urban-scale air quality management plan that also includes BC as a new indicator for protecting human health.

Introduction The purpose of this study was to compare the demographic profile, clinical characteristics and outcomes of patients during the first (W1) and Second wave (W2) of corona virus disease (COVID-19) hospitalized in high altitude rural region of Nepal. There has been limited information among high altitude patients requiring hospitalization for COVID-19 during first and second wave. Methods: This was a retrospective cross-sectional study done in high altitude rural area of Nepal (Chandannath, Jumla). All patients of age 15years and above who got admitted in our centre, Karnali Academy of Health Sciences (KAHS) were included in this study. All patients either polymerase chain reaction (PCR) positive or Rapid Detection Antigen Test (RDT antigen) positive were enrolled in the study after taking their informed consent. Data entry and analysis was done in Microsoft Excel 2010. The two waves of demographic profile, clinical characteristics and hospital outcome were correlated using the statistical analysis. Results During the W1 202 patients versus 558 patients in W2 were admitted in KAHS isolation ward over 7months period (June2020-Jan2021) and 9months period (May 2021-Feb2022) respectively. The mean age in W1 was 32.55 SD 10.2 with 69.3% male (n=140) and 30.7% being female. Whereas in W2 mean age was 46.7 SD 17.89 with male being 53% (n=296) and female 46.9%. The average hospital stay during first storm was 11days (Range 2-34days) with most patients having mild symptoms and 7.9% had moderate symptoms requiring oxygen (2-5l/min). In W2 average hospital stay was 8.14 days (Range 1-50) with most patients having moderate to severe symptoms requiring oxygen therapy with mortality of (24) 4.3%. The average patients having mild, moderate and severe symptoms requiring ICU admission in W2 were 3.12, 4.18 and 0.77 respectively. In first wave 30.7% health workers were infected and there was no mortality. Conclusion COVID-19 has affected millions worldwide resulting in Severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) with a high mortality rate due to a lack of definitive treatment. In our study, we found that males were more affected then females in both waves with ICU admission and mortality rates being higher among W2 with 4.3% mortality. Key Words: Corona Virus Disease 2019, Polymerase chain reaction, Severe Acute Respiratory Syndrome.

With the sudden outbreak of COVID 19 pandemic globally , whole world suffered from this lethal disease but the health care professionals (HCP ) including doctors, nurses, technicians, paramedical, administrative, pharmacy staff remain the main professionals directly involved in management and treatment of COVID 19 . Although in all the countries HCP did a heroic job with full dedication and selflessly saving lives of millions but during this long 2 yrs of period they also suffered with disease emotional stress, physical stress due to overwhelmed number of cases and working round the clock for patients with mental and physical tiredness. HCP are also humans and they are not immune to the psychological consequences due to COVID-19. Among all the HCPs, front-line workers were at greater risk of acquiring this deadly and devastating disease . Many reasons could be narrated for the adverse psychological outcomes in HCP including but not limited to excessive workload/ long work hours, fear of catching infection themselves or transmission the infection to the family , remaining in quarantine for few months away from the family because the mode of transmission was not clear and inadequate personal protective equipment, over-enthusiastic media news, feeling inadequately supported 1 Another important reason for such psychological impact is the very high infection rate with consequent high risk of complications related to COVID and Non COVID factors in HCP, this might lead to frustration, helplessness, adjustment issues, stigma, fear of discrimination and death or long term comorbidity in the medical staff2 . Despite the low mortality rate of 2%, the COVID-19 virus has a high transmission rate and the mortality is higher. The literature published during the outbreak of SARS almost more than a decade ago suggested that HCW are at higher risk of developing anxiety, depression, stress during these periods3 . A similar school of thought exists about the effect of COVID-19 pandemic, some studies were carried out in the past 3 months to assess the psychological impact of this disease on healthcare workers. In India, some of doctors committed suicide when they were diagnosed as COVID positive, Thousand of HCP died due to COVID19 and no official support of help had been offered to them from government. Many of doctors either were terminated from the hospital because their speciality like Dental, ENT, ophthalmology and other superspecialists were no longer needed due to high number of COVID case and many doctors resigned and worked on low salary, some doctors faced violence also form the patients relatives . These all factors contributed to significant level of mental stress among HCP and still doctors are under mental stress or post traumatic stress disorders. HCP face many problems in their personal , social and marital life as well with resultant high numbers of marital conflicts, separation and divorce among the doctors and with consequent effects on their kids and parents Conclusion : COVID–MENTANDEMIC, COVID induced socio-psychological , physical and financial stress are being faced globally and with consequent another ongoing but hidden pandemic of stress, depression , anxiety and many more psychological disorders called as COVID Mentandemic would increase and continue in near future and all governments should take necessary steps for avoidance of this COVID-MENTANDEMIC by controlling coronavirus spread, developing and delivering effective vaccine with at least 80 % coverage target and to keep themselves ready for supporting HCP psychologically for better mental health being over coming few years . Positive motivational factors like supportive and proud family and colleagues, positive role models, validation and appreciation by peers/patients, positive caretaking experience, a sense of validation of existence, knowledge, and acceptance the possible inevitability of infection need to be strengthened to boost the morale of HP. As per this study, the negatives associated with patient care include multiple needs of the patients, stigma, need for clear management plans. One solution proposed by the HP interviewed to overcome the negatives include setting up of multidisciplinary teams and screening questionnaires4. Future Perspectives : The mental health issues associated with the COVID-19 pandemic can be short-term or long-term. All Governments should provide psychological and social support to the HCP and especially to them who had COVID 19 or who suffered psychosocially and financially during the COVID era. Existing literature addresses the immediate mental health concerns only. It is important to see the long-term mental health sequels of COVID-19 infection. Nothing is known about the after-effects of novel coronavirus infection; hence, there is a need for extensive research in terms of its long term impact on HCP populations.