Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.

Eco-friendly degradation of reactive red 195, reactive blue 214, and reactive yellow 145 by Klebsiella pneumoniae MW815592 isolated from textile waste.

The water is used in many textile manufacturing steps beyond cleaning. The quantity and the significant chemical load of the effluents generated constitute the primary challenge of the textile industry. In order to discover new sustainable methods to overcome this problem, the aim of this research was to study the potential for degradation of Reactive Blue 214, Reactive Red 195, and Reactive Yellow 145 using a dye degrading bacterium. Sequencing analysis reveals it to be Klebsiella pneumoniae MW815592. This strain completely decolorized artificial effluent (200 mg/L) after 42 h at pH 9 and 46 °C. The decolorization rate increased in the presence of glucose and yeast extract (2 g). In addition, our finding revealed that the decolorization is due to biodegradation rather than adsorption on the bacterial surface.

The pattern of iron deficiency with and without anemia among medical college girl students in high altitude southern Saudi Arabia.

INTRODUCTION: The prevalence of iron deficiency, latent and symptomatic, is heterogeneous worldwide. In this study, we aim to explore the prevalence of iron deficiency, with and without anemia, among medical college females at the high Altitude Aseer region of Southwestern Saudi Arabia. METHODOLOGY: 200 female medical students were randomly sampled, between the ages of 19 and 27 years. Blood samples were collected for complete blood count (CBC) values and serum ferritin determination. Questionnaires were completed in order to collect demographics, medical history, and socioeconomic information of the participants. RESULTS: Prevalence of overall iron deficiency was high (63%, serum ferritin <20 µg/L, 52.5%, ferritin <15 µg/L). Anemia, adjusted for high altitude (defined as less than 13 g/dL was present in 41 participants (20.5%) and 12 (6.5%) have Hb <12 g/dL. Iron-deficiency anemia (Hb <13 g/dL and serum ferritin <15 µg/L) was present in 35 (17.5%). Personal and family history of anemia and poor animal product containing meals were positively correlated with the presence of iron deficiency state. Neither symptoms of anemia, nor the presence of menorrhagia correlate with the presence of iron deficiency anemia. CONCLUSION: Iron deficiency with and without anemia is a very common and condition in young females' population at high altitude. Implementing a lab method to screen for anemia on vulnerable populations is needed. Frequently asymptomatic, the primary care providers should maintain a high degree of suspicion in order to initiate screening for iron status.

Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs.

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

Mycobacterium tuberculosis Complex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan1.

Pathogen-based factors associated with tuberculosis (TB) in eastern Sudan are not well defined. We investigated genetic diversity, drug resistance, and possible transmission clusters of Mycobacterium tuberculosis complex (MTBC) strains by using a genomic epidemiology approach. We collected 383 sputum specimens at 3 hospitals in 2014 and 2016 from patients with symptoms suggestive of TB; of these, 171 grew MTBC strains. Whole-genome sequencing could be performed on 166 MTBC strains; phylogenetic classification revealed that most (73.4%; n = 122) belonged to lineage 3 (L3). Genome-based cluster analysis showed that 76 strains (45.9%) were grouped into 29 molecular clusters, comprising 2-8 strains/patients. Of the strains investigated, 9.0% (15/166) were multidrug resistant (MDR); 10 MDR MTBC strains were linked to 1 large MDR transmission network. Our findings indicate that L3 strains are the main causative agent of TB in eastern Sudan; MDR TB is caused mainly by transmission of MDR L3 strains.

[Urinary incontinence after HOLEP: Incidence, evolution and predictive factors]. / Incontinence urinaire après énucléation endoscopique de la prostate au laser Holmium : fréquence, évolution, et facteurs prédictifs de survenue.

OBJECTIVE: Assess the early morbidity after HOLEP, the urinary incontinence in particular, and specify its different types, evolution, and predictive factors. PATIENTS AND METHODS: We conducted an observational, analytical, retrospective, monocentric study including all patients undergoing surgery for benign prostatic hypertrophy (HBP) by HoLEP between November 2015 and January 2017. The data were collected pre-, per- and postoperatively. The follow-up was for 6 months. RESULTS: One hundred and seventy one patients were included. 23 patients (14.6%) had a complication according to Clavien-Dindo classification [4]: 19 (83%) Clavien 2, 1 (4%) Clavien 3b et 3 (13%) Clavien 4. At one month of the surgery, 64 (42.7%) patients had urinary incontinence of which 55 (86.1%) presented pure stress urinary incontinence. 18 (32.7%) were still incontinent at 6 months of the surgery. The delivered amount of energy during the surgery and the preoperative IIEF5 score were statistically significantly associated with the occurrence rate of stress urinary incontinence. There was no correlation between the surgeon's learning curve and the occurrence of incontinence. CONCLUSION: The occurrence rate of urinary incontinence post HoLEP might be related to the adopted surgical technique ; It is crucial to keep the patient well informed of the risk of this complication postoperatively. LEVEL OF EVIDENCE: 4.

Smear Microscopy for Diagnosis of Pulmonary Tuberculosis in Eastern Sudan.

BACKGROUND: In Sudan, tuberculosis diagnosis largely relies on clinical symptoms and smear microscopy as in many other low- and middle-income countries. The aim of this study was to investigate the positive predictive value of a positive sputum smear in patients investigated for pulmonary tuberculosis in Eastern Sudan. METHODS: Two sputum samples from patients presenting with symptoms suggestive of tuberculosis were investigated using direct Ziehl-Neelsen (ZN) staining and light microscopy between June to October 2014 and January to July 2016. If one of the samples was smear positive, both samples were pooled, stored at -20°C, and sent to the National Reference Laboratory (NRL), Germany. Following decontamination, samples underwent repeat microscopy and culture. Culture negative/contaminated samples were investigated using polymerase chain reaction (PCR). RESULTS: A total of 383 samples were investigated. Repeat microscopy categorized 123 (32.1%) as negative, among which 31 were culture positive. This increased to 80 when PCR and culture results were considered together. A total of 196 samples were culture positive, of which 171 (87.3%), 14 (7.1%), and 11 (5.6%) were M. tuberculosis, M. intracellulare, and mixed species. Overall, 15.6% (57/365) of the samples had no evidence of M. tuberculosis, resulting in a positive predictive value of 84.4%. CONCLUSIONS: There was a discordance between the results of smear microscopy performed at local laboratories in the Sudan and at the NRL, Germany; besides, a considerable number of samples had no evidence of M. tuberculosis. Improved quality control for smear microscopy and more specific diagnostics are crucial to avoid possible overtreatment.

Utilization of nano-cryptomelane for the removal of cobalt, cesium and lead ions from multicomponent system: Kinetic and equilibrium studies.

Nano-cryptomelane was prepared and characterized using SEM with mapping, HRTEM, FT-IR spectra, thermal analysis and surface area. The diameter distribution of nano-cryptomelane was found to be 4-6 nm. Sorption performance of the prepared material was studied for the removal of Co2+, Cs+ and Pb2+ from a multi-system solution of equal molar ratio, 1:1:1. The sorption capacity of nano-cryptomelane was found to be 179.6, 442.6 and 716.9 mg/g for Co2+, Cs+ and Pb2+, respectively. The kinetic studies revealed that the sorption process obeys non-linear pseudo-second-order model and is controlled by an intra-particle diffusion mechanism. The equilibrium isotherm investigations outlined that the extended Langmuir isotherm model fits the data reasonably well and it is more applicable than Freundlich multicomponent sorption isotherm. The value of diffusion coefficient for the three metal ions is in the order 10-17 m2/s which indicates the chemisorption nature of the process. The desorption percentage attains the maximum value (98.13%, 97.29 and 97.04 for lead, cesium and cobalt ions, respectively) using 0.7 mol/L of HNO3. This revealed that nano-cryptomelane can be regenerated and reused for farther sorption of Pb2+, Cs+ and Co2+ from wastewater.

Immunohistochemical Validation of Spontaneously Arising Canine Osteosarcoma as a Model for Human Osteosarcoma.

Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents one of the primary bone tumours. It is the most common primary bone tumour in dogs and man. The characterization of an appropriate natural disease animal model to study human OS is essential to elucidate the pathogenesis of the disease. This study aimed to validate canine OS as a model for the human disease by evaluating immunohistochemically the expression of markers known to be important in human OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP), desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by all tumours, while desmin, S100 and NSE were expressed variably. The findings were similar to those described previously for human OS and suggest that canine OS may represent a useful model for the study of the human disease.

Canine Mixed Mammary Tumour as a Model for Human Breast Cancer with Osseous Metaplasia.

Canine mixed mammary tumours (CMMTs) and human metaplastic breast carcinomas (HMBCs) share several histopathological features and risk factors. In both species, these tumours display epithelial and stromal components. HMBCs are rare malignant tumours, but CMMTs are one of the most common mammary tumours in dogs and are more often benign than malignant. In this study, benign (n = 88) and malignant (n = 13) CMMTs were characterized using specific antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, cytokeratin AE1/AE3, vimentin, Ki67, E-cadherin and p63. Cartilage and bone matrices associated with benign and malignant CMMTs were characterized using specific antibodies against BMP4, Runx2, Sox9 and osteopontin. The current study suggested that CMMTs are of epithelial origin, but display a myoepithelial-like differentiation. The findings suggest key roles for Sox9, Runx2 and BMP4 in chondrogenesis and bone formation in CMMTs. The high expression of osteopontin in CMMTs appears to be unrelated to tumour malignancy.

Nerve stimulator-guided pudendal nerve block vs general anesthesia for postoperative pain management after anterior and posterior vaginal wall repair: a prospective randomized trial.

STUDY OBJECTIVE: Compare the effectiveness of nerve stimulator-guided pudendal nerve block (PNB) vs general anesthesia (GA) for anterior and posterior (AP) colporrhaphy in terms of pain relief and analgesic consumption within 24 and 48 hours postoperatively. DESIGN: Prospective randomized trial. PATIENTS: Fifty-seven patients whose ages ranged between 20 and 53 years scheduled to undergo AP colporrhaphy due to the presence of cystorectocele. INTERVENTIONS: Patients were randomly assigned into 2 groups receiving either nerve stimulator-guided PNB (n = 28) or GA (n = 29). A total volume of 0.7 mL/kg of the local anesthetic mixture was injected at 4 sites. MAIN RESULTS: Both groups were similar with respect to age, weight, height, and surgery duration. There was a significant difference in average pain scores within the first and second postoperative days (P values = .005 and .004, respectively). Total analgesic consumption (ketoprofen and tramadol) was significantly lower in the PNB within the first (P values = .018 and .010) and second postoperative days (P values = .041 and .011), respectively. Return to normal daily activity was significantly (P< .0001) shorter in the PNB group compared with the GA group (3.6 days vs 12.2 days). A total of 71.4% of the patients in the PNB group were satisfied compared with 27.8% in the GA group (P< .0001). Surgeon satisfaction was significantly higher in the PNB group (82.1% vs 34.5%, P< .0001). CONCLUSION: This randomized controlled trial demonstrated that nerve stimulator-guided PNB could be used as an alternative to GA for AP repair of stages I and II prolapse because it is associated with less postoperative pain and analgesic consumption, in addition to shorter duration of recovery.

Early Results of Brachial Arterio-Arterial Prosthetic Loop (AAPL) for Hemodialysis.

BACKGROUND: Vascular access has always been the Achilles heel of hemodialysis. Advances in health care have brought forward patients requiring treatment who have no veins suitable for creation of arteriovenous fistula (AVF) or insertion of central venous catheters. Use of an artery as permanent vascular access has been reported by many authors. This study reports brachial AAPL as an efficient and safe access for hemodialysis patients with central venous occlusion. METHODS: Between January 2011 and December 2014, 35 brachial arterio-arterial prosthetic loops (AAPL) were created. The age of patients ranged between 27 and 72 years, with a mean age of 52.8 years. RESULTS: The primary patency rates were 87.9%, 70.4%, and 38.8% at 12, 24, and 36 months, respectively. The secondary patency was 90.7%, 80.3%, and 67.6% at 12, 24, and 36 months, respectively, after successful thrombectomy in seven cases. CONCLUSION: Mid-term follow-up results demonstrate patency rates comparable with those of the synthetic AVF. The rate of complications, although slightly higher than that with traditional synthetic AVF, is still acceptable in this population with no option for access.

Statistical controversies in clinical research: end points other than overall survival are vital for regulatory approval of anticancer agents.

There is an ongoing debate about the relative merits of overall survival (OS) and other metrics that can be used as primary end points in cancer clinical trials. Although survival time is arguably the most objective metric for assessing the efficacy of anticancer treatment, OS as a clinical-trial end point needs to be conceptually distinguished from increased survival time as a goal desired by patients, clinicians and public-health policy makers. OS presents several drawbacks as a primary end point that threatens to hamper further drug development, including the increase in the number of patients and the much longer follow-up required in a clinical trial. In many settings of first-line therapy for metastatic disease, median OS is currently two to four times longer than median progression-free survival. As a result, the analysis of OS may be increasingly confounded by the effect of salvage therapies used after disease progression. In this review, we use straightforward statistical reasoning and examples from the oncology literature to argue that OS should no longer be the primary end point of most future phase III cancer clinical trials that aim at assessing the efficacy of novel therapies in the setting of metastatic disease.

Severe peritonitis caused by Citrobacter freundii and successful treatment with double antibiotic coverage.

Serratia, Pseudomonas/Providencia, indole-positive Proteus/Acinetobacter/Morganella, Citrobacter, Enterobacter and Hafnia group of organisms cause peritoneal dialysis (PD)-related peritonitis with high morbidity and mortality. Peritonitis caused by Citrobacter freundii is uncommon, and it may lead to catheter removal despite antimicrobial treatment. We describe a case of PD-related peritonitis caused by C. freundii, which was successfully treated with double antibiotic coverage.

Pentavalent technetium-99m-dimercaptosuccinic acid [Tc-99m (V) DMSA] brain SPECT: does it have a place in predicting survival in patients with glioblastoma multiforme?

Pentavalent technetium-99m dimercaptosuccinic acid (Tc-99m (V) DMSA) is reported as a useful tool for detection of residual or recurrent gliomas. We aimed to investigate the prognostic value of Tc-99m (V) DMSA brain SPECT in patients with glioblastoma multiforme (GBM). 40 patients [21 males and 19 females; mean age 48.6 ± 12.2 years] with GBM were included. Tc-99m (V) DMSA brain SPECT was done after surgery and before onset of radiation therapy or chemotherapy (Baseline study), at 4-6 weeks and at 6 months as a follow-up after therapy. The end point of the study was clinical follow-up for 2 years and/or death. 4-6 weeks after therapy, 40 and 60 % had negative and positive Tc-99m (V) DMSA for viable tumor tissues respectively (P = 0.09). At 6 months follow-up, 62.5 % of (V) DMSA negative patients and 12.5 % of the positive subjects were responders (P = 0.001). The median over-all survival (OS) of all patients was 12.3 month [range 5-24 month]. Patients with positive (V) DMSA had worse survival (8.87 month) compared to the negative ones (16.67 month) (P = 0.0001). Multivariate Cox regression analysis showed that Tc-99m (V) DMSA brain SPECT studies at 4-6 weeks and 6-months follow-up were independent prognostic factors for survival [OR 1.069; 95 % CI 1.417-2.174; P = 0.03 and OR 1.055; 95 % CI 0.821-1.186; P = 0.01 respectively]. Stratification of tumors into risk groups based on prognostic parameters may improve outcome by altering or intensifying treatment methods. Technetium-99m dimercaptosuccinic acid brain SPECT may have an additional prognostic role in patients with GBM which needs further evaluation in larger future series.

Large granular lymphocytic leukemia presenting late after solid organ transplantation: a case series of four patients and review of the literature.

Post-transplantation lymphoproliferative disorder (PTLD) is a significant complication of solid organ transplantation. Most PTLD is of the B-cell subtype, although T-cell subtype PTLD uncommonly occurs. T-cell PTLDs are usually aggressive neoplasms and shorten patient and allograft survivals significantly. We present a single-center case series of 4 patients who developed T-cell large granular lymphocytic (LGL) leukemia, a rare T-cell PTLD characterized by large granular lymphocytes that have characteristic azurophilic granules and a highly variable clinical course.

Cardiac toxicity in breast cancer patients.

AIM: To asses cardiac toxicity post radiotherapy in left cancer breast patients with different fractionations. METHODS: This is a prospective randomized study conducted at Kasr El-Ainy Center of Clinical Oncology and Nuclear Medicine (NEMROCK). Cardiological assessment using RTOG toxicity criteria was done for left sided breast cancer patients after at least five years of conformal radiation therapy. There were two arms of radiation, conventional (50Gy/25sttt/5 Ws) and hypofractionation (42.5 Gy /16 fractions /3 1/5 weeks). RESULTS: Thirty patients were included in each arm. After a median follow up of 62 months (range 60 to 72), cardiac dysfunction developed more in the conventional arm but was insignificant (P value =0.36). Grade I & II toxicity was 83.3 vs 70% and grade III was 3.3% in the hypofractionated arm only. The rate of localregional tumor relapse at 5 years was similar (3.3%). CONCLUSION: Hypofractionated radiotherapy decreased cardiac toxicity though not statistically significant, however it is more cost effective and time consuming. KEYWORDS: breast cancer, cardiac toxicity, hypofractionation, Egypt.