High-Temporal-Resolution Kinetic Modeling of Lung Tumors with Dual-Blood Input Function Using Total-Body Dynamic PET.

The lungs are supplied by both the pulmonary arteries carrying deoxygenated blood originating from the right ventricle and the bronchial arteries carrying oxygenated blood downstream from the left ventricle. However, this effect of dual blood supply has never been investigated using PET, partially because the temporal resolution of conventional dynamic PET scans is limited. The advent of PET scanners with a long axial field of view, such as the uEXPLORER total-body PET/CT system, permits dynamic imaging with high temporal resolution (HTR). In this work, we modeled the dual-blood input function (DBIF) and studied its impact on the kinetic quantification of normal lung tissue and lung tumors using HTR dynamic PET imaging. Methods: Thirteen healthy subjects and 6 cancer subjects with lung tumors underwent a dynamic 18F-FDG scan with the uEXPLORER for 1 h. Data were reconstructed into dynamic frames of 1 s in the early phase. Regional time-activity curves of lung tissue and tumors were analyzed using a 2-tissue compartmental model with 3 different input functions: the right ventricle input function, left ventricle input function, and proposed DBIF, all with time delay and dispersion corrections. These models were compared for time-activity curve fitting quality using the corrected Akaike information criterion and for differentiating lung tumors from lung tissue using the Mann-Whitney U test. Voxelwise multiparametric images by the DBIF model were further generated to verify the regional kinetic analysis. Results: The effect of dual blood supply was pronounced in the high-temporal-resolution time-activity curves of lung tumors. The DBIF model achieved better time-activity curve fitting than the other 2 single-input models according to the corrected Akaike information criterion. The estimated fraction of left ventricle input was low in normal lung tissue of healthy subjects but much higher in lung tumors (∼0.04 vs. ∼0.3, P < 0.0003). The DBIF model also showed better robustness in the difference in 18F-FDG net influx rate [Formula: see text] and delivery rate [Formula: see text] between lung tumors and normal lung tissue. Multiparametric imaging with the DBIF model further confirmed the differences in tracer kinetics between normal lung tissue and lung tumors. Conclusion: The effect of dual blood supply in the lungs was demonstrated using HTR dynamic imaging and compartmental modeling with the proposed DBIF model. The effect was small in lung tissue but nonnegligible in lung tumors. HTR dynamic imaging with total-body PET can offer a sensitive tool for investigating lung diseases.

Optic Chiasm Glioma in an Older Adult Patient.

We present a case of an adult patient experiencing progressive visual loss. An initial presentation was concerning for neuromyelitis optica with optic chiasm involvement. However, persistent contrast enhancement observed in follow-up brain and orbit images raised suspicion for optic tract malignant neoplasm. Histopathological evolution of optic nerve biopsy confirmed the diagnosis of an optic chiasm glioma. The patient was then referred to oncology for chemotherapy.

Single monoclonal spike characterized as double monoclonal gammopathy in a patient with multiple myeloma: A rare finding.

Multiple myeloma (MM) is associated with the secretion of a unique monoclonal protein (M-protein) due to overproduction of immunoglobulin (Ig) by a clone of abnormally proliferating plasma cells. However, in 4% of the cases more than one M-protein can be found. This category of gammopathies is called "double monoclonal gammopathies." Here, we present a rare case of MM with double monoclonal gammopathy, where the presence of both M-proteins was observed in the single sharp peak on capillary zone electrophoresis (CZE). Further the interference of Hook effect is also discussed. Double monoclonal gammopathies need to be identified to increase diagnostic accuracy and reliability, and to get a better understanding of the disease pathogenesis and progression.

Anterior and posterior ischemic optic neuropathy in a child with focal segmental glomerulosclerosis on hemodialysis.

BACKGROUND: Ischemic optic neuropathy (ION) is exceedingly rare in children on dialysis, resulting from poor perfusion of the optic nerve, and presents as sudden acute painless vision loss. CASE-DIAGNOSIS/TREATMENT: We report the case of a 3-year-old male with stage 5 chronic kidney disease (CKD 5) due to focal segmental glomerulosclerosis (FSGS) status post-bilateral nephrectomy on chronic hemodialysis who had acute loss of vision several hours after a hemodialysis session. Earlier that day, he had a drop in blood pressure intra-dialysis to 89/67 mmHg, with at home blood pressures ranging 90/60 to 150/100 mmHg. The patient was treated with tight blood pressure control to maintain blood flow and prevent blood pressure lability, received high-dose corticosteroids with a corticosteroid taper, and placed on high-dose erythropoietin for neuroprotective effect. He regained partial vision beginning approximately 1 month after presentation. CONCLUSIONS: The exact cause of our patient's simultaneous bilateral anterior and posterior ION, confirmed via MRI and fundoscopic examination, is unclear; however, is likely secondary to a combination of fluctuating blood pressure, anemia, anephric status, and hemodialysis. This highlights the need for close blood pressure monitoring, management of anemia, and more diligent ophthalmologic screening in pediatric patients on chronic hemodialysis.

Rectal Melanoma: Rare Cancer with Grave Prognosis.

Malignant melanoma of the rectum is an exceedingly rare type of cancer with an aggressive presentation, comprising up to 4% of all anorectal cancers. Presentation of this cancer tends to occur in individuals in their late 80s, with nonspecific symptoms such as anal pain or rectal bleeding. Diagnosing rectal melanoma, especially in early stages, is difficult due to its amelanotic presentation and lack of pigmentation, which results in poor remission rates and prognosis. Furthermore, surgical treatment is difficult as these types of malignant melanomas tend to spread along submucosal planes; thus, complete resections are impractical, especially if caught later. In this case report, we present the radiological and pathological features as seen in a 76-year-old man diagnosed with rectal melanoma. Based on his presentation of a heterogeneous bulky anorectal mass with extensive local invasion, initial impressions were colorectal carcinoma. However, surgical pathology found the mass to be a c-KIT+ melanoma, with positive SOX10, Melan-A, HMB-45, and CD117 biomarkers. While the patient was treated with imatinib, the melanoma was too widespread and aggressive, leading to progression and ultimately death.

Post-mastectomy radiotherapy for women with early breast cancer and one to three positive lymph nodes.

BACKGROUND: Continual improvement in adjuvant therapies has resulted in a better prognosis for women diagnosed with breast cancer. A surrogate marker used to detect the spread of disease after treatment of breast cancer is local and regional recurrence. The risk of local and regional recurrence after mastectomy increases with the number of axillary lymph nodes affected by cancer. There is a consensus to use radiotherapy as an adjuvant treatment after mastectomy (postmastectomy radiotherapy (PMRT)) in women diagnosed with breast cancer and found to have disease in four or more positive axillary lymph nodes. Despite data showing almost double the risk of local and regional recurrence in women treated with mastectomy and found to have one to three positive lymph nodes, there is a lack of international consensus on the use of PMRT in this group. OBJECTIVES: To assess the effects of PMRT in women diagnosed with early breast cancer and found to have one to three positive axillary lymph nodes. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov up to 24 September 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs). The inclusion criteria included women diagnosed with breast cancer treated with simple or modified radical mastectomy and axillary surgery (sentinel lymph node biopsy (SLNB) alone or those undergoing axillary lymph node clearance with or without prior SLNB). We included only women receiving PMRT using X-rays (electron and photon radiation), and we defined the radiotherapy dose to reflect what is currently being recommended (i.e. 40 Gray (Gy) to 50 Gy in 15 to 25/28 fractions in 3 to 5 weeks. The included studies did not administer any boost to the tumour bed. In this review, we excluded studies using neoadjuvant chemotherapy as a supportive treatment before surgery. DATA COLLECTION AND ANALYSIS: We used Covidence to screen records. We collected data on tumour characteristics, adjuvant treatments and the outcomes of local and regional recurrence, overall survival, disease-free survival, time to progression, short- and long-term adverse events and quality of life. We reported on time-to-event outcome measures using the hazard ratio (HR) and subdistribution HR. We used Cochrane's risk of bias tool (RoB 1), and we presented overall certainty of the evidence using the GRADE approach. MAIN RESULTS: The RCTs included in this review were subgroup analyses of original RCTs conducted in the 1980s to assess the effectiveness of PMRT. Hence, the type and duration of adjuvant systemic treatments used in the studies included in this review were suboptimal compared to the current standard of care. The review involved three RCTs with a total of 829 women diagnosed with breast cancer and low-volume axillary disease. Amongst the included studies, only a single study pertained to the modern-day radiotherapy practice. The results from this one study showed a reduction of local and regional recurrence (HR 0.20, 95% confidence interval (CI) 0.13 to 0.33, 1 study, 522 women; low-certainty evidence) and improvement in overall survival with PMRT (HR 0.76, 95% CI 0.60 to 0.97, 1 study, 522 women; moderate-certainty evidence). One of the other studies using radiotherapy techniques that do not reflect modern-day practice reported on disease-free survival in women with low-volume axillary disease (subdistribution HR 0.63, 95% CI 0.41 to 0.96, 1 study, 173 women). None of the included studies reported on PMRT side effects or quality-of-life outcome measures. AUTHORS' CONCLUSIONS: Based on one study, the use of PMRT in women diagnosed with breast cancer and low-volume axillary disease indicated a reduction in locoregional recurrence and an improvement in survival. There is a need for more research to be conducted using modern-day radiotherapy equipment and methods to support and supplement the review findings.

Complete and Uneventful Recovery in a Case of Lymphocytic Hypophysitis Causing a Third Nerve Palsy.

Lymphocytic hypophysitis (LH) is a neuroendocrine disorder characterised by autoimmune inflammation of the pituitary gland with resultant pituitary dysfunction. Rarely, the presenting symptom can be diplopia due to irritation of the third, fourth, or sixth cranial nerves secondary to cavernous sinus involvement of the mass or increased intracranial pressure. We describe the case of a healthy, 20-year-old female with a pupillary sparing third nerve palsy, who was subsequently diagnosed with LH after an endoscopic transsphenoidal biopsy of the mass. She was treated with hormone replacement therapy and corticosteroids, resulting in full resolution of symptoms with no recurrence to date. To our knowledge, this is the first report of a third nerve palsy due to definitive biopsy proven LH. Despite its rarity, the unique presentation and favourable evolution of this case should aid clinicians in its timely recognition, appropriate workup, and treatment.

CENTRAL RETINAL VEIN OCCLUSION FOLLOWING BNT162B2 (PFIZER-BIONTECH) COVID-19 MESSENGER RNA VACCINE.

PURPOSE: Coronavirus disease 2019 has had a wide-ranging public health impact, contributing to at least five million deaths globally at the time of this report. Although thromboembolic events following coronavirus disease 2019 vaccination have been an ongoing concern, only a limited number of ophthalmic manifestations have been reported to date. METHODS: A detailed history, hypercoagulable workup, best-corrected visual acuity (BCVA), Humphrey visual field, dilated fundus examination, and multimodal imaging including optical coherence tomography, fundus fluorescein angiography, and fundus photography were obtained. RESULTS: A 27-year-old woman was diagnosed with central retinal vein occlusion a few days after her first dose of the BNT162b2 (Pfizer-BioNTech) coronavirus disease 2019 vaccine. Detailed elicitation of her history and a full hypercoagulable workup did not reveal any primary risk factors that could have explained her disease process. After the patient received the second dose, her symptoms deteriorated significantly and worsening peripapillary hemorrhage were seen on dilated fundus examination. The patient was treated with intravitreal injections of ranibizumab and followed closely, which showed improvement in her central retinal vein occlusion. CONCLUSION: Given the chronology of the patient's condition, it is believed that the central retinal vein occlusion that occurred as a result of the first dose was exacerbated by an intense immunological reaction after the second dose. The severity of this complication, despite its rarity, must be emphasized and weighed in but should not preclude the extensive benefits of vaccination.

Unraveling the Possibilities of Monoclonal Protein Migration, Identification, and Characterization in SPEP on Capillary Zone Electrophoresis.

Serum protein electrophoresis (SPEP) is a method by which proteins present in serum are separated into different fractions based on their molecular weight and electric charge. Presence of M spike, composed of monoclonal protein, on electrophoretogram is a characteristic finding that can be seen in monoclonal gammopathies like multiple myeloma. M spike is most commonly seen in the gamma region however, the M-spike can be observed in fraction other than the Y fraction as well i.e. in the beta region and rarely alpha region. Here we have enumerated few cases where M protein has been seen in fractions other than the gamma region. Thus one needs to be cautious about the variable appearance of M-spike during interpretation of SPEP as some physiological proteins if elevated can also give rise to similar spike sometimes referred as pseudo monoclonal pattern.

Recovery of Complete Blindness and Internal Ophthalmoplegia After Transsphenoidal Decompression of Pituitary Apoplexy.

We report the case of a 64-year-old male who developed sudden onset of bilateral no light perception vision and bilateral total internal ophthalmoplegia after pituitary apoplexy. He underwent transsphenoidal pituitary decompression. Four months after the surgery, the patient recovered excellent functional vision (20/25) in one eye, though with significant residual visual field loss. He regained full extraocular motility bilaterally.

Exploring the therapeutic potential of Neem (Azadirachta Indica) for the treatment of prostate cancer: a literature review.

Background and Objective: Multiple studies have demonstrated the medical potency of plant extracts and specific phytochemicals as therapeutics for prostate cancer (PCa) patients. Of note, the Neem plant known for its role as an antibiotic and anti-inflammatory is underexplored with an untapped potential for further development. This review focuses on extracts and phytochemicals derived from the Neem tree (Latin name; Azadirachta indica), commonly used throughout Southeast Asia for the prevention and treatment of a wide array of diseases including cancer. To date, there are more than 130 biologically active compounds that have been isolated from the Neem tree including azadirachtin, nimbolinin, nimbin, nimbidin, nimbidol, which have demonstrated a wide range of biological activities including anti-microbial, anti-fertility, anti-inflammatory, anti-arthritic, hepatoprotective, anti-diabetic, anti-ulcer, and anti-cancer effects. Very few scientific reports focus on the benefits of Neem in PCa, even though this herb has been used to prevent the disease and its progression for years in complementary and alternative medicine. Methods: We used the search engines like PubMed, InCommon and Google using the key words: "Neem", "Cancer", "Prostate Cancer" and related words to find the information and data within the time frame from 1980-2022 for our article study. Key Content and Findings: Here, we provide an overview of Neem extracts and phytochemical derivatives with a focus on their known potential and ability to inhibit specific cellular signaling pathways and processes which drive PCa incidence and progression. Conclusions: The information presented here indicate that Neem and its derivatives have a therapeutic potential for the treatment of PCa when used as a single agent or in combination with conventional chemotherapeutics.

Chest wall perforator flap to partially reconstruct central mound of breast tissue - evolution of the technique.

We describe the use of chest wall perforator flap (CWPF) to reconstruct the central mound of breast tissue in women presenting with central/retro areolar breast cancer. We describe the results of seven patients (median age, 59 years) with a median follow-up of 9 months. We were able to conserve the breast in all except one woman who was found to have extensive DCIS. Two patients were taken back to theatre, one for a washout of infected seroma and second for a wound debridement. There was no flap loss or donor site complications in our series. We were able to conserve the breast, maintain aesthetic contour of the central mound along with projection and achieve excellent cosmetic outcome for our patients. Partial breast reconstruction using CWPF provides an oncologically safe and cosmetically superior alternative in selected women with breast cancer needing central wide local excision.

Phycoremediation of milk processing wastewater and lipid-rich biomass production using Chlorella vulgaris under continuous batch system.

This study compiles the results of phycoremediation of milk processing wastewater (MPWW) and production of lipid-rich Chlorella vulgaris biomass using a continuous batch system operated for 12-wks. After a 4-wks interval, a new MPWW was loaded photobioreactor to provide appropriate nutrient supply to algae. Results indicated that MPWW supported the algal growth efficiently and the maximum algal growth was recorded in the ranges of 400.36 to 421.58 mg L-1 during 4-wk's of the cultivation cycle. Average reduction in total nitrogen, TN (45.82-69.18%); nitrate, NO3 (93.32-94.54%); total ammonium nitrogen, TAN (92.94-94.54%); sulphate, SO4-2 (85.13-87.34%); total phosphorus (75.09-78.78%); and biochemical oxygen demands, BOD (89.53-92.40%) was recorded during 12-wks phycoremediation of MPWW. Harvested algal biomass (dry weight basis, DW) exhibited a significant content of total sugar (45.5%) and total lipid (39.7%). The lipid profiling results indicated the presence of palmitic acid (39.9%), oleic acid (21.08%), linoleic acid (13.13%), and other C18 compounds in algal biomass, suggesting the suitability of MPWW for Chlorella vulgaris cultivations. Algal biomass exhibited a high heating value (MJ/Kg of DW) in the range of 17.3 to 25.1, comparable to other lignocellulose biomass to be used for bioenergy purposes. Results of this study indicate that MPWW could be utilized as a valuable medium for Chlorella vulgaris cultivation under a circular economy approach: wastewater treatment and bioenergy feedstock production. The effect of controlled environmental conditions on algal growth behavior and lipid composition in biomass, while using MPWW as a medium, could be investigated in future studies.

Optic neuritis secondary to the Pfizer-BioNTech-162b2 COVID-19 vaccine managed with plasmapheresis: A case report and review.

The COVID­19 pandemic has had a significant public health impact globally, with inoculation now paramount in limiting the spread of the disease. Although the safety and efficacy profiles of COVID­19 vaccines are well documented, it is upon the medical community to be aware of adverse effects to appropriately advise and treat patients. We report the case of a 39­year­old female who was hospitalized with optic neuritis (ON) 1 week after her second dose of the Pfizer­BioNTech (BNT162b2) COVID­19 vaccine. The patient did not have any significant medical history, including personal or familial history of multiple sclerosis or any other demyelinating disease, other than prior COVID­19 infection. She had since made a full recovery and tested negative at the time of hospitalization for ON. Over the course of her admission, the patient's visual acuity (VA) deteriorated from 20/400 to no light perception. After methylprednisolone was ineffective, she was started on plasmapheresis (PLEX) therapy which resulted in mild improvement of VA. To our knowledge and after a thorough PubMed literature search, this is the first reported case of isolated ON associated with COVID­19 vaccination.

Impact of Preinfection Left Ventricular Ejection Fraction on Outcomes in COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) has high infectivity and causes extensive morbidity and mortality. Cardiovascular disease is a risk factor for adverse outcomes in COVID-19, but baseline left ventricular ejection fraction (LVEF) in particular has not been evaluated thoroughly in this context. We analyzed patients in our state's largest health system who were diagnosed with COVID-19 between March 20 and May 15, 2020. Inclusion required an available echocardiogram within 1 year prior to diagnosis. The primary outcome was all-cause mortality. LVEF was analyzed both as a continuous variable and using a cutoff of 40%. Among 396 patients (67 ± 16 years, 191 [48%] male, 235 [59%] Black, 59 [15%] LVEF ≤40%), 289 (73%) required hospital admission, and 116 (29%) died during 85 ± 63 days of follow-up. Echocardiograms, performed a median of 57 (IQR 11-122) days prior to COVID-19 diagnosis, showed a similar distribution of LVEF between survivors and decedents (P = 0.84). Receiver operator characteristic analysis revealed no predictive ability of LVEF for mortality, and there was no difference in survival among those with LVEF ≤40% versus >40% (P = 0.49). Multivariable analysis did not change these relationships. Similarly, there was no difference in LVEF based on whether the patient required hospital admission (56 ± 13 vs 55 ± 13, P = 0.38), and patients with a depressed LVEF did not require admission more frequently than their preserved-LVEF peers (P = 0.87). A premorbid history of dyspnea consistent with symptomatic heart failure was not associated with mortality (P = 0.74). Among patients diagnosed with COVID-19, pre-COVID-19 LVEF was not a risk factor for death or hospitalization.

Expression of barley oxalate oxidase confers resistance against Sclerotinia sclerotiorum in transgenic Brassica juncea cv Varuna.

Sclerotinia Stem Rot (SSR) caused by the oxalic acid (OA)-secreting necrotrophic fungal pathogen Sclerotinia sclerotiorum, causes significant yields losses in the crop Brassica sps. Oxalate oxidase (OxO) can metabolize OA to CO2 and H2O2. Degradation of OA during the early phase of fungal-host interaction can interfere with the fungal infection and establishment processes. The present study demonstrates the potential of barley oxalate oxidase (BOxO) gene in conferring stable resistance against stem rot in a productive and highly susceptible Brassica juncea cv Varuna under field conditions. Four stable, independent, single-copy transgenic lines (B16, B17, B18, and B53) exhibited a significant reduction in the rate of lesion expansion i.e. 11-26%, 39-47%, and 24-35% reproducibly over the three-generation i.e. T2, T3, and T4 respectively. The enhanced resistance in the transgenic lines correlated with high OxO activity, accumulation of higher levels of H2O2, and robust activation of defense responsive genes upon infection by S. sclerotiorum.

Ocular myasthenia gravis - How effective is low dose prednisone long term?

INTRODUCTION: Controversy persists on the best treatment to control ocular myasthenia gravis (OMG) and reduce conversion to generalized myasthenia gravis (GMG). We hypothesized that low dose prednisone could accomplish both in a cohort of OMG patients followed after three years. METHODS: We reviewed the records of 168 patients who presented with OMG. Our study included 103 of the OMG patients who met inclusion criteria, requiring follow up for a minimum of 3 years without disease generalization. Low dose prednisone was defined as ≤7.5 mg per day. The main outcome was having single vision without ptosis blocking vision, measured by binocular single vision (BSV) and upper lid position. We also analyzed late progression to GMG. RESULTS: Of 87 patients treated with prednisone, chronic low dose prednisone alone restored BSV in 47 patients (46% of all patients) without GMG. Pyridostigmine monotherapy restored BSV in 11/14 patients (11% of all patients). Other immunomodulatory therapy (OIT) was needed in 38 patients (37%). Medical therapy maintained BSV at last evaluation (mean follow up 8.2 ± 5.0 years) in 93 patients (90%). GMG developed in 10 patients (10%) during the follow-up period. CONCLUSION: In OMG patients who do not generalize before 3 years, chronic long term prednisone at lower doses is moderately effective in maintaining optimum BSV. However, OIT are commonly required in these patients. In these OMG patients receiving prednisone and/or OIT, conversion to GMG after three years of disease is uncommon.

Neoadjuvant Cabozantinib in Renal-Cell Carcinoma: A Brief Review.

Nephrectomy is the reference-standard treatment for renal-cell carcinoma (RCC). For patients with unresectable disease, tumor may be shrunk by using chemotherapy, thereby permitting surgical resection, which can be curative. We provided neoadjuvant cabozantinib, the preferred tyrosine kinase inhibitor for advanced RCC of poor and intermediate risk, to two patients with initially unresectable RCCs. In both patients, this led to tumor shrinkage of > 50% after 4 months of therapy, which permitted surgical resection. Both tumor specimens also showed strong pathologic tumor response. The robust responses observed with cabozantinib, even at reduced doses, suggest it to be an effective neoadjuvant option in RCC. Our novel experience with neoadjuvant cabozantinib, combined with our review of the use of cabozantinib in RCC, indicates that providing preoperative cabozantinib to facilitate potentially curative surgical resection has good results and should be further explored.

Levels of different subtypes of tumour-infiltrating lymphocytes correlate with each other, with matched circulating lymphocytes, and with survival in breast cancer.

PURPOSE: Breast cancer tumour-infiltrating lymphocytes associate with clinico-pathological factors, including survival, although the literature includes many conflicting findings. Our aim was to assess these associations for key lymphocyte subtypes and in different tumour compartments, to determine whether these provide differential correlations and could, therefore, explain published inconsistencies. Uniquely, we also examine whether infiltrating levels merely reflect systemic lymphocyte levels or whether local factors are predominant in recruitment. METHODS: Immunohistochemistry was used to detect tumour-infiltrating CD20+ (B), CD4+ (helper T), CD8+ (cytotoxic T) and FoxP3+ (regulatory T) cells in breast cancers from 62 patients, with quantification in tumour stroma, tumour cell nests, and tumour margins. Levels were analysed with respect to clinico-pathological characteristics and matched circulating levels (determined by flow-cytometry). RESULTS: CD4+ lymphocytes were the most prevalent subtype in tumour stroma and at tumour edge and CD8+ lymphocytes were most prevalent in tumour nests; FoxP3+ lymphocytes were rarest in all compartments. High grade or hormone receptor negative tumours generally had significantly increased lymphocytes, especially in tumour stroma. Only intra-tumoural levels of CD8+ lymphocytes correlated significantly with matched circulating levels (p < 0.03), suggesting that recruitment is mainly unrelated to systemic activity. High levels of stromal CD4+ and CD20+ cells associated with improved survival in hormone receptor negative cases (p < 0.04), while tumour nest CD8+ and FoxP3+ cells associated with poor survival in hormone receptor positives (p < 0.005). CONCLUSIONS: Lymphocyte subtype and location define differential impacts on tumour biology, therefore, roles of tumour-infiltrating lymphocytes will only be unravelled through thorough analyses that take this into account.

Cell free DNA: revolution in molecular diagnostics - the journey so far.

Cell free DNA (cf-DNA) refers to all non -ncapsulated DNA present in the blood stream which may originate from apoptotic cells as a part of the physiological cell turnover, or from cancer cells or fetal cells. Recent studies have highlighted the utility of cfDNA analysis for genetic profiling of cancer, non-invasive prenatal testing besides many other clinical applications. In our review we discuss the sources of cfDNA in the body, the techniques most commonly being used for its isolation and analysis, the applications of cfDNA testing and the associated pros-cons. We conclude that for prenatal testing, cfDNA analysis provides an effective, non-invasive and safer alternative to traditional amniocentesis and chorionic villus sampling tests. Also, in cancer patients, cfDNA analysis is useful for genetic profiling and follow-up during treatment. However, standardization of methods of isolation and analysis has become crucial for the success of widespread use of cfDNA analysis.