Expression of PD1 and PDL1 as immune-checkpoint inhibitors in mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) has remained incurable in most patients. The expression of PD-L1 as a prognostic and predictive marker has not been fully evaluated in MCL. The current study aimed to determine PD-1/PD-L1 expression in MCL specimens and its significance as an immune check point inhibitor. METHODS: This retrospective study was conducted on the formalin-fixed paraffin-embedded blocks of 79 confirmed MCL patients based on immunohistochemistry (IHC). The IHC method was used to stain patient samples for PD1 and PDL1. Positive PD-1/PD-L1 expression was defined as moderate to strong or memberanous or memberanous/cytoplasmic staining in at least 5% of tumor and/or 20% of associated immune cells. Tumor aggressiveness was determined based on Ki67 and variant. RESULTS: The mean age of the patients was 60.08 ± 10.78 years old. Majority of the patients were male. The prevalence of aggressive tumor was 25%. Positive PD1 and PDL1 expression were identified in 12 (15.0%) and 3 (3.8%) of tumor cells, respectively. PD1 and PDL1 were positive in zero (0%) and 7 (8.9%) of background cells, respectively. There was no significant difference in terms of study parameters between positive and negative groups for both PD1 and PDL1 proteins. PD1 tumor cell percentage was negatively correlated with age (r = -0.254, p = 0.046). CONCLUSION: Our results suggest that neither PD-1 nor its ligands represent relevant targets for MCL treatment. Age may impact the efficiency of immune checkpoint inhibitors and could be related to the increased incidence of MCL with age.

Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients. METHODS: A total of 11 patients diagnosed with COVID-19-induced ARDS who were admitted to the intensive care units (ICUs) of two hospitals enrolled in this study. The patients were critically ill with severe hypoxemia and required mechanical ventilation. The patients received three intravenous infusions (200 × 106 cells) every other day for a total of 600 × 106 human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases). FINDINGS: There were eight men and three women who were 42 to 66 years of age. Of these, six (55%) patients had comorbidities of diabetes, hypertension, chronic lymphocytic leukemia (CLL), and cardiomyopathy (CMP). There were no serious adverse events reported 24-48 h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48-96 h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2-7 days (average: 4 days), one patient who had signs of acute renal and hepatic failure was discharged from the ICU on day 18, and the last patient suddenly developed cardiac arrest on day 7 of the cell infusion. Significant reductions in serum levels of tumor necrosis factor-alpha (TNF-α; P < 0.01), IL-8 (P < 0.05), and C-reactive protein (CRP) (P < 0.01) were seen in all six survivors. IL-6 levels decreased in five (P = 0.06) patients and interferon gamma (IFN-γ) levels decreased in four (P = 0.14) patients. Four patients who had signs of multi-organ failure or sepsis died in 5-19 days (average: 10 days) after the first MSC infusion. A low percentage of lymphocytes (< 10%) and leukocytosis were associated with poor outcome (P = 0.02). All six survivors were well with no complaints of dyspnea on day 60 post-infusion. Radiological parameters of the lung computed tomography (CT) scans showed remarkable signs of recovery. INTERPRETATION: We suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. Patients that develop sepsis or multi-organ failure may not be good candidates for stem cell therapy. Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS.

Intravenous Immunoglobin Utilization Study in a Teaching Hospital.

BACKGROUND: Intravenous immunoglobulin (IVIG) is an immunomodulating agent that has several actions. The aim of this study was to investigate the indications of IVIG according to available evidence and the cost in our center. METHODS: This retrospective study was conducted between September 2017 and June 2018 at a teaching hospital affiliated with Iran University of Medical Sciences, Tehran, Iran. Patients' demographic data and disease, indication for IVIG use, its dosage and treatment regimen and previous and concurrent treatments were assessed. The collected data were compared with the present criteria for the pattern of IVIG usage. The last version of Lexicomp® was used as the reference for indications of the administrated drug and its dosage. RESULTS: A total of 119 patients received IVIG during the study period. The wards with the most frequent IVIG prescription were the neurology (46.2%) and neonatal intensive care unit (21%). The most common reasons of IVIG therapy were various inflammatory neurological disorders. IVIG was used in 22, 43 and 54 cases according to on-label, off- label and other indications, respectively. The total price was higher for off-label indications for IVIG ($254343.75) than on-label indications ($152625). As well, $107250 was exhausted for cases in which there was not sufficient evidence. CONCLUSION: One important aspects of this study was the use of IVIG in cases other than on-label indications. Although a number of studies support IVIG therapy in some diseases, further trials are needed to establish efficacy and safety in these fields.

Role of Telemedicine in Pace of Consultation and Physicians' Satisfaction in Thoracic Surgery ICU.

BACKGROUND: Despite various applications of tele-ICU, there are still many questions about its costs and advantages in ICU. Some of its advantages are accelerating consultations and bringing physicians' satisfaction from tele-consultation outcomes. The aim of this study is to discuss these advantages. MATERIALS AND METHODS: Initially a telemedicine network was implemented and in the case of having no related specialist, the physicians used telemedicine network to perform specialized tele-consultation to thoracic surgery ICU patients. ICU patient's documents during a year before tele-consultation were studied and delay time in consultation was recorded and compared between the two phases. Finally, the physicians' satisfaction with tele-consultation was evaluated. RESULTS: Fifty-eight tele-consultations in various medical fields were carried out, of which 27 were neurology cases. From the time of receiving a consultation request to its performance, the mean time was 1.3 days in tele-consultation. Tele-consultations were given 2.5 times faster than face to face method. In evaluation of physicians' satisfaction, 82.75% of them were fully satisfied from tele-consultation, 12.06% were partly satisfied and 5.17% were not satisfied. CONCLUSION: Since the length of hospitalization in ICU is crucial due to heavy costs of treatment, high risk of contamination and limited beds, performing timely consultation is a key factor in reducing hospitalization period. Tele-consultation in thoracic surgery ICU not only accelerates patient care, but also results in higher physician satisfaction.

Home spirometry: Assessment of patient compliance and satisfaction and its impact on early diagnosis of pulmonary symptoms in post-lung transplantation patients.

Telemedicine is useful in monitoring patients, and in particular those, such as lung transplant recipients, suffering from chronic illnesses. This prospective cohort study was conducted on 15 lung transplant recipients. The patients provided physicians with data from spirometry as well as their clinical respiratory symptoms via SMS messages. In cases where spirometry results or clinical symptoms required follow-up, the monitoring physician contacted the patient according to guidelines and gave appropriate instructions. Qualitative assessment of satisfaction showed that the sense of increased support from medical staff was rated highest (92.9%). Telespirometry is an efficient method of monitoring lung transplant recipients which leads to patient satisfaction, compliance, adherence to study and sense of security. Nevertheless, for optimal implementation of this method, thorough training of both medical staff and patients is required.

Use of Bispectral Index Score for Interventional Bronchoscopy Procedures.

BACKGROUND: Interventional bronchoscopic procedures are novel diagnostic and therapeutic methods in pulmonology, which may be unpleasant and dangerous to the patients; therefore, sedation and in some cases general anaesthesia are recommended. But adjusting the level of sedation is a challenge. In this study we intended to define a range of bispectral index (BIS) score suitable for these procedures. MATERIALS AND METHODS: All patients referred to our interventional bronchoscopy unit were enrolled in the study. Sedation was induced using midazolam, sufentanil, and propofol with the patient breathing spontaneously. The target level of sedation was to reach a Ramsay sedation score of 3 and patient tolerance in performing the procedure. The BIS score was recorded at baseline and every five minutes thereafter. Correlation between different BIS values, propofol dosage, duration of procedure, and awakening time was evaluated. RESULTS: A total of 70 patients were enrolled in this study with a mean age of 50± 16 years and 34 (48.6%) of them were males. The mean baseline BIS was 96±3.7, and the mean time to reach "stable BIS" ("stable time") was 7.9±6 minutes. The mean "stable BIS" was 52±13.5 and 70% of patients had stable BIS between 40 and 60. CONCLUSION: BIS is a useful objective tool for evaluation of sedation, which can guide us through bronchoscopy and related procedures. According to our observational study, reaching the mean BIS level of 52±13.5 is required to prevent complications and ensure feasibility of the procedure.