Alterations in lymphocyte subsets and monocytes in patients diagnosed with SARS-CoV-2 pneumonia: a mini review of the literature.

OBJECTIVE: Complete blood count parameters are frequently altered in COVID-19 patients. Leucopenia and lymphopenia are the most common findings. This is not specific to COVID-19 as similar alterations are found in various other viral infections. This work is intended to summarize the evidence regarding white blood cell and lymphocyte subset alterations in COVID-19 and their clinical implications. MATERIALS AND METHODS: A PubMed search was conducted to identify relevant original studies. Articles not available in English or referring exclusively to pediatric patients were excluded. The study was designed as a narrative review from its inception. RESULTS: Complete white blood cell number and lymphocytes may be reduced in COVID-19 patients. Circulating CD4+ cells (helper T lymphocytes), CD8+ cells (cytotoxic T lymphocytes), regulatory T cells and natural killer (NK) cells may be reduced, with a greater reduction observed in critically ill patients. CD4+ and regulatory cell deficiencies may contribute to the cytokine storm and subsequent tissue damage observed in severe COVID-19 infection. NK and CD8+ cell deficiency might delay infection clearance. These aberrations of cellular immunity may contribute significantly to the pathogenesis of the disease. Alterations observed in monocyte function can also be implicated as they are effector cells responsible for tissue damage and remodeling. B cell dysfunction and maturation abnormalities have also been reported, suggesting that the virus also impairs humoral immunity. CONCLUSIONS: Lymphocyte subset abnormalities may be useful prognostic biomarkers for COVID-19, with circulating CD8+ cell count being the most promising as a predictor of severe disease requiring mechanical ventilation and mortality.

Prevalence and significance of mediastinal lymphadenopathy in patients with Severe Acute Respiratory Syndrome Corona Virus-2 infection.

Severe Acute Respiratory Syndrome Corona Virus-2 is the causative factor of Coronavirus Disease 2019. Early in the pandemic, mediastinal lymphadenopathy was not considered to be a significant radiologic finding of the SARS-COV-2 disease. Nevertheless, most recent studies associate mediastinal lymphadenopathy with more severe COVID-19 disease and poorer patient outcomes.

Poly (ADP-ribose) polymerase 1 mRNA levels strongly correlate with the prognosis of myelodysplastic syndromes.

Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0.011) and the cytogenetic risk (P=0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a significant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus 'not reached' for low PARP1 levels, P=0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.

The role of obesity in the immune response during sepsis.

BACKGROUND/OBJECTIVES: Sepsis is one of the most important causes of mortality in the developed world, where almost two-thirds of the population suffer from obesity. Therefore, the coexistence of both conditions has become frequent in clinical practice and a growing number of clinical studies attempts to examine the potential effect of obesity on sepsis with controversial results up to now. The present study investigates how obesity influences the immune response of septic patients, by assessing the number and activation state of adipose tissue macrophages, serum and adipose tissue tumor necrosis factor-alpha (TNFα) levels and plasma oxidative stress markers. SUBJECTS/METHODS: The study included 106 patients, divided into four groups (control n=26, obesity n=27, sepsis n=27 and sepsis and obesity n=26). The number of macrophages in subcutaneous and visceral adipose tissue (SAT and VAT) and their subtypes (M1 and M2) were defined with immunohistochemical staining techniques under light microscopy. TNFα mRNA levels were determined in SAT and VAT using real-time reverse transcription-PCR. Serum levels of TNFα were determined with sandwich enzyme-linked immunosorbent assay. Plasma oxidative stress was evaluated using selective biomarkers (thiobarbituric acid-reactive substances (TBARS), protein carbonyls and total antioxidant capacity (TAC)). RESULTS: Sepsis increased the total number of macrophages and their M2 subtype in (VAT), whereas obesity did not seem to affect the concentration of macrophages in fat. Obesity increased TNFα mRNA levels (P<0.05) in VAT as well as the plasma TBARS (P<0.001) and protein carbonyls (P<0.001) in septic patients. The plasma TAC levels were decreased and the serum TNFα levels were increased in sepsis although they were not influenced by obesity. CONCLUSIONS: Obesity is associated with elevated TNFα adipose tissue production and increased oxidative stress biomarkers, promoting the proinflammatory response in septic patients.

Good's syndrome and pure white cell aplasia complicated by cryptococcus infection: A case report and review of the literature.

Thymomas can present with a variety of paraneoplastic manifestations, mostly of autoimmune origin, including Good's syndrome when there is associated hypogammaglobulinemia. Although pure red cell aplasia is a recognised complication of thymoma, selective white cell aplasia is very rare, particularly in Good's syndrome. Lethal opportunistic infections are a feature of Good's syndrome, usually occurring in those patients with associated severe T lymphocyte defects. Although the cryptococcus is a recognised fungal pathogen in patients with other causes of CD4+ T cell lymphopenia, surprisingly this complication has not been reported in patients with Good's syndrome. We now describe a 70 year old man with Good's syndrome and pure white cell aplasia who presented with disseminated cryptococcosis, and provide an up-to-date review of the relevant literature. Despite meningeal involvement our patient recovered after combined treatment with intravenous globulin, granulocyte stimulating growth, corticosteroids and antifungal therapy.

Magnetic resonance imaging and image analysis of post - radiation changes of bone marrow in patients with skeletal metastases.

PURPOSE: To evaluate the post-radiation lesions of the bone marrow with magnetic resonance imaging (MRI) and image analysis in patients with bone metastases undergoing radiation therapy (RT). METHODS: Thirty-five patients with bone metastases were studied from June 2008 to December 2010. All patients had osseous metastases from various primary malignancies and underwent palliative RT. MRI was performed in a Philips Gyroscan Intera 1T scanner at the beginning of RT and 12-18 days later. T1-TSE, T2-TSE and short tau inversion recovery (STIR) sequences were used. All images obtained were evaluated for early post-radiation lesions. Additionally, 1st and 2nd order textural features were extracted from these images and were introduced into a probabilistic neural network (PNN) classifier in order to create an automated classification system for those lesions. RESULTS: Changes of signal intensity in T1-TSE, T2-TSE and STIR sequences were evaluated for the presence of edema, fatty conversion of the bone marrow or areas of hemorrhage within the limits of the irradiated area. The automated classification system showed positive results in correctly discriminating the post-radiation lesions that MRI revealed. The overall classification accuracy for discriminating between pre-radiation and post-radiation lesions was 93.2%. Furthermore, the overall classification accuracy for discriminating between post-radiation lesions was 86.67%. CONCLUSION: It seems that MRI can evaluate the degree of early therapy-induced bone marrow lesions observed during the first 18 days from the beginning of RT. The proposed neural network-based classification system might be used as an assisting tool for the characterization of these lesions.

Skeletal metastases: an update of the literature with pictorial review.

The skeleton is one of the common places were many tumors metastasize. Skeletal metastases may profoundly affect the patients' quality of life by making them unable to move freely and help themselves, while in some cases impingement upon the CNS structures can cause neurologic symptoms. Early diagnosis of bone metastases is therefore very important in order to prevent severe debilitating conditions. We review the role of different diagnostic methods available for the detection of bone metastases, as well as their response to treatment: bone scintigraphy, plain films, computed tomography (CT) and magnetic resonance imaging (MRI). The role of positron emission tomography (PET) and PET/CT is also discussed.

Impact of European legislation on marketed pesticides--a view from the standpoint of health impact assessment studies.

The very significant impact of European legislation (Directive 91/414/EEC) on the authorization of plant protection products is reviewed herein, which has resulted in withdrawal of 704 active substances (AS) out of 889 assessed so far. The list of currently approved 276 AS includes 194 AS "existing" in the market before 1993 and 82 "new" AS introduced during the last 15 years. Results of toxicity characterization of the approved AS are also summarized, utilizing several well-known databases. Although significant data gaps exist for a rather large part of the approved AS, it is found that 84 AS are positive for at least one health effect (after chronic and/or acute exposure) including carcinogenicity, reproductive and neuro-developmental disorders, as well as endocrine disruption. The toxicity characterization results of this study are compared to those of recent assessments by other organizations (KemI, the Swedish Chemicals Agency, and the Pesticide Safety Directorate of the UK), where interpretation and use is made of AS "cut-off" criteria foreseen in new EU legislation. These studies report a comparatively smaller AS number with positive toxicity characterization. The possibility of some additional AS withdrawal in the near future, combined with the rather small rate of new AS introduction (approx. 5 per year) suggest that the list of approved AS over the next 10-15 years may not change very drastically. Consideration of the above trends is necessary and instructive in evaluating results of existing health impact assessment (HIA) studies, as well as in planning new ones. Due to the very drastic change in the number and type of marketed AS, that took place within the past 8-9years, it is suggested that new HIA studies (based on epidemiological data after year 2000) should focus on a rather short time frame and, therefore, on appropriate cohort groups, e.g. young children. For the same reason, results of epidemiological studies of the past (involving banned AS) should be carefully interpreted and used with caution.

MRI investigation for neurofibromatosis type 1 lesions during pregnancy--a case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder of the nervous system that causes tumor growth on the nerves, skin changes and bone deformities, and it is reported to be associated with adverse perinatal outcome in pregnant women. CASE: We report a case of MRI investigation of a pregnant woman with a known NF1 disease who showed exacerbation of skin lesions during pregnancy. No dangerous lesions that could compromise pregnancy outcome were detected, thus allowing the pregnancy to continue to term uneventfully. CONCLUSION: MRI has strong indications for the follow-up of pregnant patients with neurofibromatosis as it can detect lesions that can serve as risk factors for pregnancy complications.

Quantitative evaluation of magnetic resonance imaging (MRI) abnormalities in subclinical hepatic encephalopathy.

BACKGROUND/AIMS: Cirrhotic patients often demonstrate high signal intensity on T1-weighted magnetic resonance (MRI) images in basal ganglia with accumulation of manganese being the predominant causing factor. In these patients, electrophysiological tests and especially electroencephalogram (EEG) are considered to be the most sensitive methods in detection of subclinical hepatic encephalopathy. The aim of this study is to correlate MRI findings with biochemical parameters and EEG alterations in cirrhotic patients without clinically overt encephalopathy. METHODOLOGY: Twenty-two cirrhotic patients (16 males and 6 females, mean age of 65.2 +/- 9.5 years), classified according to Child-Pugh score, were submitted to brain MRI, neurological assessment (including psychometric tests and EEG) and complete biochemical testing. None of them had any clinical signs of brain dysfunction. MRI findings were evaluated both qualitatively (normal, mild, moderate and severe) and quantitatively with the ROI method. EEG alterations were also classified as normal, mild, moderate and severe. RESULTS: Statistical analysis revealed a significant linear association between EEG grading and MRI signal intensity (r2=0.248, p=0.035). Among clinical and biochemical parameters, overall Child-Pugh score and albumin levels were identified as significant predictors of the MRI signal intensity (p=0.006 and p=0.021 respectively). CONCLUSIONS: Although further investigation must be performed to confirm the clinical impact of brain MRI in hepatic cirrhosis, our study strongly suggests that MRI alterations are good predictors of liver and brain dysfunction in cirrhotic patients.

Co-existence of Chiari malformation type I and Epstein-Barr virus meningoencephalitis in a 3-year-old child: case report and review of the literature.

In the present report we describe an unusual case of a 3-year-old girl who was admitted to our hospital with Epstein-Barr virus meningoencephalitis. Brain magnetic resonance imaging revealed diffuse abnormalities in white matter and Chiari I malformation with cervical and thoracic hydro-syringomyelia.

Multiple spinal epidural abscesses extending to the whole spinal canal.

Spinal epidural abscess (SEA) is a rare life-threatening disease mostly affecting patients with an altered immune system. It presents as a sequela of adjacent infection or hematogenous spread. MRI is the method of choice in evaluating patients with suspected SEAs and should always include the whole spinal canal, excluding the exceedingly rare possibility of multiple epidural collections. We present a rare case of a patient with no predisposing factors suffering from multiple SEAs, extending to the whole spinal canal.

Changing trends in the management of Klatskin tumor.

BACKGROUND/AIMS: To evaluate the long-term outcome of a multidisciplinary approach for advanced Klatskin tumor involving the hepatic hilus. METHODOLOGY: A retrospective analysis was undertaken in 110 patients between 1993 and 2003. The patients were divided into Group A (n=42) and Group B (n=58). Group A patients underwent local excision of the tumor and Group B patients underwent combined tumor and liver resection with or without resection of the regional vascular structures. On admission, all patients underwent percutaneous transhepatic biliary drainage. Where hepatectomy was planned, portal vein branch ligation and transection was done ipsilateral to the liver lobe where the tumor was present. An arterial catheter was introduced into the hepatic artery at the end of the surgery, for adjuvant locoregional immunochemotherapy, which was carried out in all patients. The second-stage resectional surgery was carried out 35 days later. RESULTS: The overall mean survival for Group A patients was 29 months (range 14 to 76). The mean disease-free survival was 28 months (range 10-52). Five-year survival rate was 5% and five-year disease-free survival was 0%. The overall mean survival for Group B patients was 39 months (range 28 to 79). The mean disease-free survival was 32 months (range 17-72). Five-year survival rate was 20% and five-year disease-free survival was 10%. CONCLUSIONS: The concept of a multidisciplinary approach has significantly improved survival in patients with a grave disease like Klatskin tumor.

Two-stage liver surgery for advanced liver metastasis synchronous with colorectal tumor.

BACKGROUND/AIMS: To evaluate the efficacy of two-stage surgery and multidisciplinary approach, in the treatment of primary colorectal cancer, synchronous with advanced liver metastases. METHODOLOGY: Sixty-two patients who underwent two-stage surgery for advanced metastatic liver disease synchronous with colorectal tumor were studied. In the first-stage surgery, the primary colorectal tumor was resected. Depending on the location of the main tumor mass, ligation and transection of the relevant (right or left) main portal vein branch was done. Subsequently, the metastatic nodules in the contralateral lobe were ablated by microwave therapy. An arterial jet port catheter was also introduced into the hepatic artery via the gastroduodenal artery for locoregional chemoimmunotherapy. Two days after the first-stage surgery locoregional transarterial targeting chemoimmunotherapy was given. The second-stage hemihepatectomy was carried out forty to forty-five days after the initial surgery. As an adjuvant treatment locoregional targeting chemoimmunotherapy was carried out in all patients via the arterial chemoport. RESULTS: Mean survival was 66+/-4 months. There were no operative deaths. CONCLUSIONS: Two-stage liver surgery including, portal vein branch ligation, microwave ablative therapy and transarterial targeting locoregional chemoimmunotherapy is the best treatment for advanced, synchronous metastatic liver disease of colorectal origin. It results in an increase in the overall survival of these patients with good postoperative quality of life, which encourages the hepato-biliary surgeon to venture upon this herculean task thus increasing the resectability rate of the tumor.

Mono-bloc total spleno-pancreaticoduodenectomy for pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study.

BACKGROUND/AIMS: To evaluate, the early and long-term results of mono-bloc spleno-pancreatic and vascular resection for advanced carcinoma of the head of the pancreas, with portal-mesenteric venous invasion. METHODOLOGY: In a prospective, randomized trial, fifty-six patients with advanced carcinoma of the head of the pancreas with vascular invasion were studied. Patients were randomly divided in two groups A and B. Group A patients underwent an en-bloc spleno-pancreatic and vascular resection. Group B patients underwent a palliative gastro-biliary bypass. Patients in both groups were subjected to adjuvant locoregional chemoimmunotherapy, through an arterial catheter introduced into the superior mesenteric artery via a jejunal arterial branch. RESULTS: The 2- and 5-year survival rates for Group A patients were 81.8% and 18.5%. The respective percentages for disease-free survival were 60.6% and 0%. Two-year survival for group B was nil. CONCLUSIONS: Mono-bloc spleno-pancreaticoduodenectomy and regional vascular resection and reconstruction, with adjuvant locoregional chemoimmunotherapy leads to substantial prolongation of survival and optimization of quality of life.

New frontiers in the management of advanced hepatocellular carcinoma. "A new look to an old problem".

BACKGROUND/AIMS: To evaluate the benefits of two-stage liver surgery with main portal branch ligation and transection combined with transarterial targeting locoregional neo and adjuvant immunochemotherapy in patients suffering from hepatocellular carcinoma. METHODOLOGY: 43 consecutive patients underwent two-stage liver surgery for advanced hepatocellular carcinoma. First we performed ligation and transection of the main portal vein branch corresponding to the liver lobe occupied by the tumor. Subsequently we introduced an arterial jet port catheter towards the hepatic artery via the gastroduodenal artery. After locoregional transarterial targeting immunochemotherapy regimen the patient underwent a second laparotomy for hemihepatectomy. Following surgery, locoregional transarterial targeting immunochemotherapy was given to all patients via the arterial port of the gastroduodenal artery as an adjuvant treatment. RESULTS: Mean survival was 41 months. There were no operative deaths. CONCLUSIONS: Two-stage liver surgery and transarterial targeting locoregional immunochemotherapy is the favorable option of treatment for advanced hepatocellular carcinoma. It not only results in an increase in the overall survival of these patients, but also increases the rate of resectability of these tumors by the hepatobiliary surgeon.

13q deletion in chronic lymphocytic leukemia: characterization of E4.5, a novel chromosome condensation regulator-like guanine nucleotide exchange factor.

We report the characterization of a new gene (E4.5) that maps at chromosome band 13q14.3, a chromosomal area frequently deleted in chronic lymphocytic leukemia (CLL) and in other lymphoid malignancies. E4.5 gene encodes for a 4 kb mRNA expressed in various tissues and has an open reading frame of 531 amino acids. The predicted E4.5 protein shows strong homology with the human regulator of chromosome condensation (RCC1) protein, the principal GTP exchange factor for Ran protein. The E4.5 protein contains a BTB domain in its N-terminus, a protein-protein interaction motif. Therefore, we propose that E4.5 is a new member of the RCC1-related guanine nucleotide exchange factor (GEF) family with potent interaction with other proteins and unknown function. Until now, no tumor suppressor genes have been mapped in the 13q14.3 minimal deleted region (MDR) in patients with CLL. It has been proposed that loss of the 13q14.3 MDR may contribute to lymphoid neoplasia by altering the expression/function of genes located on 13q14.3 outside the MDR. The E4.5 is one of these genes with a potential role in the pathogenesis of CLL.