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Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

Takotsubo syndrome (TSS) is a reversible, acute cardiomyopathy with transient heart failure, often secondary to other disorders. A 64-year-old woman, with no history of ischemic heart disease, was admitted to the emergency department after developing sudden-onset dyspnea after a planned acupuncture treatment for back pain. Acute echocardiography showed decreased left ventricular function with basal hypercontraction and apical akinesia and was interpreted, and treated, as acute heart failure. When the attending cardiologist arrived, the patient still had dyspnea with a declining blood pressure (97/65 mmHg) and tachycardia (111/minute). The cardiologist suspected a tension pneumothorax induced by the penetration of an acupuncture needle to the apex of the lung, as well as secondary TSS cardiomyopathy. An acute chest X-ray was performed, which showed a large left-sided rim pneumothorax. The attending surgeon placed a chest tube in the left 6th intercostal space in the midaxillary line, and the patient reported immediate pain relief and improvement in her dyspnea. The patient’s clinical condition improved, and a control X-ray showed that the lung was fully expanded. The chest tube was removed, but after a few minutes, the patient developed a massive subcutaneous emphysema in the upper chest and in the face and her clinical condition deteriorated rapidly. A new chest tube was inserted, and the patient’s tachycardia diminished, with her clinical condition improving immediately. The patient remained hospitalized for the next seven days. After three continuous days without any escaped air in the chest tube, the tube was removed, and the patient was observed for another 48 hours. This time, the removal was without any complications and within two days, the patient was ready for discharge. The follow-up echocardiography showed complete recovery of left ventricular function.

Objectives: To report the spectrum of spinal dysraphism presenting in pediatric patients admitted to the Department of Neurosurgery Lady reading hospital Peshawar. Material & Methods: A descriptive case series was conducted and total of 89 patients (age between 2 months to 12 years) were included who underwent the surgical treatment. All patients were examined for clinical and radiological diagnosis of spinal dysraphism. Results: The average age at treatment was 23 ± 39.77 months. The most recurring (52.8%) presenting symptom was the swelling on the back followed by lower limb weakness. Meningocele was reported in 11.2%, myelomeningocele in 47.2%, myelomeningocele & hydrocephalus in 12.4%, tethered cord syndrome in 25.8%, and diastematomyelia 3.4% of patients. Excision combined with the repair was done in 58.4%, release & repair done in 29.2% and endoscopic third ventriculostomy/ventriculoperitoneal shunts with the repair were done in 12.4% patients. Cerebrospinal fluid leak was reported in 3.7%, wound infection in 4.5% and mortality was reported in 3.4% patients. Conclusion: Overall, a good outcome was reported in the majority of our patients. Surgical procedures like myelomeningocele’s excision & repair, tethered cord’s release & repair, and ETV/VP shunt in patients with hydrocephalus can lead to satisfactory clinical outcomes.

Objectives: The study aimed to ascertain the clinical outcome and complications of endoscopic endonasal transsphenoidal surgery (ETSS) for pituitary adenomas. Material & Methods: A retrospective study conducted at the Department of Neurosurgery Prime Teaching Hospital Peshawar, Pakistan. Pituitary adenoma was diagnosed in 89 patients on MRI Brain with contrast and post-surgical biopsy. Post-surgical outcomes and complications were documented. Results: Out of 89 patients, 54% were male, and 46% female patients. The mean age was 42 ± 5 years. Headache was reported in 92% as a most common presentation, followed by decreased visual acuity in 62 %, amenorrhea in 22%, and acromegaly in 29% of patients. Overall, the symptoms related to surgical improvement were observed in 72% of patients. A good surgical outcome was observed in 80% of patients with microadenomas, as compared to the patients with macroadenomas. The most common complication was the transient diabetes insipidus followed by Cerebrospinal fluid (CSF) leak and post-operative hematoma. Conclusion: Endoscopic endonasal transsphenoidal surgery (ETSS) is a safe, less invasive, cosmetically effective technological advancement for pituitary adenomas.

Background Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. Methods This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival. Results Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. Conclusions AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.

Background Coronavirus disease 2019 (COVID-19) causes an atypical acute respiratory distress syndrome associated with thromboembolism and high shunt fraction. Shunt may be intrapulmonary, or extrapulmonary. Handheld devices are increasingly being used for point-of-care ultrasound, but their use to characterize shunt has not been reported. Objectives Determine the feasibility of using handheld ultrasound to detect and characterize anatomical substrates of hypoxia and deep vein thrombosis (DVT) in patients with COVID-19 suspected to have severe shunt. Methods A handheld ultrasound device (iQ, Butterfly, USA) was used to perform lung ultrasound, vascular assessment for DVT, and limited transthoracic echocardiography (TTE) with color Doppler and saline microbubble contrast in patients with COVID-19 suspected to have severe shunt. Images were reassessed by an independent reviewer. Results After screening 40 patients, six patients who fulfilled the inclusion criteria were identified. Two were excluded because palliation had been initiated. So, four patients were studied. Interpretable images were obtained in all cases. Interobserver agreement was good. All patients had abnormal lung ultrasound (lung ultrasound score range 17–22). Identified lung pathology included interstitial syndrome with light beams and small peripheral consolidation (4), lobar consolidation (1), and pleural effusion (1). Abnormal echocardiographic findings included interatrial shunt (2), intrapulmonary shunt (1), and dilated right ventricle with tricuspid valve regurgitation (1). Significant DVT was not detected. Conclusion Use of handheld ultrasound to perform combined lung ultrasound, DVT ultrasound, and limited TTE with color Doppler and saline microbubble contrast is feasible, and may be able to characterize shunt in critically hypoxic patients. Serial studies could be used to monitor changes in shunt. Further studies are required to determine whether this can guide treatment to improve the outcomes of patients with refractory hypoxia.

The Aedes albopictus mosquito is a vector of several deadly diseases of humans and domesticated animals. Usually, synthetic insecticides are used for mosquito control. The excessive use of synthetic insecticides is hazardous for humans and the environment. Therefore, there is a need to develop environment-friendly and novel mosquito larvicides. In the current study, we evaluated larvicidal and bite protection properties of Seriphidium brevifolium essential oil (SBEO) and its active constituents against this mosquito. SBEO and its active constituents, α, β-thujone, and limonene, were toxic to A. albopictus, with LC50 values of 21.43, 45.99, 47.38, and 49.46 μg/mL. The cream formulation of EO at 5 % (w/v) provided complete protection against mosquito bites until 70 min after application. Among the EO constituents tested, α and β-thujone showed considerable protections against mosquito bites but lower as compared with the whole oil. Furthermore, 1:1 combinations of active constituent α-thujone and β-thujone and 1:1:1 combinations of α-thujone, β-thujone, and limonene displayed a synergistic effect against the larvae. Particularly, the EO and its active constituents were safer to Poecilia reticulata a mosquito predator, with LC50 ranging from 3934.33 to 14,432.11 μg/mL. Our current study indicated that SBEO and some of its constituents can be used for the control of A. albopictus mosquito, as a novel alternative to hazardous synthetic insecticides and to overcome the problem of increasing insecticides resistance.

Purpose African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T. Patients and methods OS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan–Meier and Cox proportional hazard methodologies. Results Median follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68–0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57–0.86, P PSA-matched set. Median OS was longer in African Americans than in Caucasian men for both analysis sets, e.g., 35.3 and 25.8 months, respectively, in the PSA-matched set. Similar results were observed in the all patient set. Differences were larger when treatment began at lower baseline PSA; curves were more similar among patients with higher baseline PSA. In patients with baseline PSA below the median, the HR was 0.52 (95% CI: 0.37–0.72, P P Conclusion In this exploratory analysis of a registry including nearly 12% African American men with mCRPC, OS was significantly different between African Americans and Caucasians, indicating further research is warranted.

Background: Refractive errors and eye diseases are the main core issues in the jail inmates in Pakistan and especially in Punjab province but with best efforts the ophthalmic disorders can be controlled with the help of better screening process for refractive errors, presbyopia, low vision and the general ophthalmic disorders that are found among the jail inmates. The over burden of these ailments can be minimized following a comprehensive screening methods time to time using slandered guidelines approved by WHO. Methodology: A plan was executed for basic necessary screening process to find out the ophthalmic diseases and vision problems. A team of ophthalmologist, optometrists and ophthalmic technicians visited inmates in the jail who presented with any eye problem in this 1-day screening. Auto refraction and manual retinoscopy was done. Visual cut off point was 6/12. Ophthalmic eye medication and glasses (spectacles) was provided free of cost. Results: a total of 270 inmates were examined in the eye camp. The study showed prevalence of refractive errors 4% with a significant high ratio of presbyopia 34% as 79%of inmates were more than 40 year of age. Prevalence of other main eye disease was: conjunctivitis 3%, glaucoma 1% and cataract 2%. Conclusions: There is an urgent need to look into matter of presence the eye diseases and refractive errors found among jail inmates as they fall in the category of marginalized community and the health care provided with ease has no provision the general eye health care. So it is an important issue to lodge a comprehensive effective initiative for the provision of that need mentioned above and a training program for the medical staff of jail hospitals to screen out this community for effective screening knowledge in Primary Eye care.

Purpose: Previous phases of trachoma mapping in Pakistan completed baseline surveys in 38 districts. To help guide national trachoma elimination planning, we set out to estimate trachoma prevalence in 43 suspected-endemic evaluation units (EUs) of 15 further districts. Methods: We planned a population-based trachoma prevalence survey in each EU. Two-stage cluster sampling was employed, using the systems and approaches of the Global Trachoma Mapping Project. In each EU, residents aged ≥1 year living in 30 households in each of 26 villages were invited to be examined by trained, certified trachoma graders. Questionnaires and direct observation were used to evaluate household-level access to water and sanitation. Results: One EU was not completed due to insecurity. Of the remaining 42, three EUs had trichiasis prevalence estimates in ≥15-year-olds ≥0.2%, and six (different) EUs had prevalence estimates of trachomatous inflammation—follicular (TF) in 1–9-year-olds ≥5%; each EU requires trichiasis and TF prevalence estimates below these thresholds to achieve elimination of trachoma as a public health problem. All six EUs with TF prevalences ≥5% were in Khyber Pakhtunkhwa Province. Household-level access to improved sanitation ranged by EU from 6% to 100%. Household-level access to an improved source of water for face and hand washing ranged by EU from 37% to 100%. Conclusion: Trachoma was a public health problem in 21% (9/42) of the EUs. Because the current outbreak of extremely drug-resistant typhoid in Pakistan limits domestic use of azithromycin mass drug administration, other interventions against active trachoma should be considered here.

Weaning failure from mechanical ventilation may be due to lung de-recruitment or weaning-induced pulmonary oedema (WIPO). Both can be diagnosed by lung ultrasound (LUS) and transthoracic echocardiography (TTE), respectively. We conducted a prospective observational study, combining TTE and LUS, to determine if LUS alone may identify elderly patients at high risk of weaning or extubation failure. Before and at the end of spontaneous breathing trials (SBT) in 40 elderly patients, we prospectively performed LUS and TTE. Extubation was decided by an independent operator. LUS included global and anterolateral LUS score. TTE included measurement of E/A and E/Ea ratios to determine LV filling pressures. SBT LUS scores for prediction of weaning outcome and for the diagnosis of WIPO were studied. Weaning or extubation failure was observed in 45% (95% CI 28–61) of patients. ROC analysis for ability of global SBT LUS to predict weaning/extubation failure and extubation failure found AUC of 0.80 and 0.81, respectively. AUC for anterolateral SBT LUS to predict weaning/extubation failure and extubation failure was 0.79 and 0.81, respectively. Increased LV filling pressure during SBT was observed without increase of anterolateral LUS score. Inversely, increase of anterolateral LUS was observed without increased filling pressure and was associated with extubation failure. Global and anterolateral SBT LUS were not correlated to E/Ea. In elderly patients, global and anterolateral LUS scores were associated with weaning and extubation failures while echocardiographic indices of filling pressures were not. ClinicalTrials.gov No. NCT03261440.

Aims: To describe the incidence and identify prognostic factors of central nervous system (CNS) adverse events (AEs) and any AEs (CNS, skin rash, or fracture) and evaluate the healthcare resource u...

Zinc is an essential trace element which is involved in controlling oxidative stress, growth and immune system by regulating inflammatory cytokines. Gouty arthritis is the inflammation of joints and tissues caused by the accumulation of monosodium urate crystals.This study involved the oral administration of zinc oxide nanoparticles at a various concentration (5 ppm, 10 ppm, and 20 ppm) and study their antioxidant and anti-gout effects on Balb/C mice. Various parameters such as ROS, superoxide, peroxide, catalase, TBARS, RFTs, LFTs, lipid profile and blood count were studied.ZnO nanoparticles at the concentrations of 10 and 20 ppm were significant (P 0.001) in reducing serum uric acid concentration thus treating gouty arthritis. Reactive oxygen species and thiobarbituric acid reactive substances were significantly increased in comparison to zinc oxide nanoparticles treated groups. Furthermore, blood count and LFTs also showed the effectiveness of zinc oxide in the reduction of hyperuricemia. Histopathological analysis showed no apparent changes in liver, kidney and muscles tissues.Zinc oxide nanoparticles can be effective in reducing oxidative stress and the treatment of gouty arthritis.

Background: von Hippel-Lindau (VHL) syndrome is a multisystem neoplastic disorder involving eyes, central nervous system, kidneys, spine, and other tissues. A retinal capillary hemangioma (RCH) is the earliest manifestation of the VHL disease in most cases.Areas covered:This paper aims to provide an up-to-date review of the current literature about von Hippel-Lindau syndrome. Molecular background, systemic and ocular features of the diseases as well as the utility of newer imaging modalities in diagnosis and monitoring of ocular VHL disease have been described. Besides, we have discussed newer treatment modalities and therapeutic targets.Conclusion: Modern imaging technologies like optical coherence tomography and optical coherence tomography angiography are tools of the trade, in making an appropriate diagnosis and monitoring disease activity and response to treatment. Peripheral RCH may be treated using laser photocoagulation in tumors up to 3000 µm. Vascular endothelial growth factor suppression can help in reducing tumor activity and stabilize the tumor size; however, it does not regress the RCH.

Right-to-left (RTL) interatrial shunt (IAS) may complicate select cases of COVID-19 pneumonia. We describe the use of serial imaging to monitor shunt in critically ill patients. A 52-year-old man presented with COVID-19 pneumonia. Hypoxia worsened despite maximal medical therapy and non-invasive ventilation. On day 8, saline microbubble contrast-enhanced transthoracic echocardiography revealed a patent foramen ovale (PFO) with RTLIAS. Invasive ventilation was initiated the next day. The course was complicated by intermittent severe desaturation without worsening aeration or haemodynamic instability, so PFO closure was considered. However, on day 12, saline microbubble contrast-enhanced transoesophageal echocardiography excluded RTLIAS. The patient was extubated on day 27 and discharged home 12 days later. Thus, RTLIAS may be dynamic and changes can be detected and monitored by serial imaging. Bedside echocardiography with saline microbubble contrast, a simple, minimally invasive bedside test, may be useful in the management of patients with severe hypoxia.

Background: Endothelial nitric oxide synthase (eNOS) and potassium voltage-gated channel subfamily J member 11 (KCNJ11) could be the candidate genes for coronary artery disease (CAD). This study investigated the relationship of the eNOS (rs1799983) and KCNJ11 (rs5219) polymorphisms with the presence and severity of CAD in the North Indian pop- ulation. Methods: This study included 300 subjects, 150 CAD cases and 150 healthy controls. Single nucleotide polymorphism was evaluated by Polymerase chain reaction and Restriction fragment length polymorphism (PCR-RFLP). Analysis was performed by SPSS (version 21.0). Results: We observed that KK genotype of KCNJ11E23K (rs5219) polymorphism (P=0.0001) genotypes and K allele (P=0.0001) was found to be a positive risk factor and strongly associated with CAD. In the case of eNOSG894T (rs1799983) there was no association found with CAD. Conclusion: These results illustrate the probability of associations between SNPs and CAD although specific genetic pol- ymorphisms affecting ion channel function and expression have still to be clarified by further investigations involving larger cohorts. Keywords: Coronary Artery Disease (CAD); endothelial nitric oxide synthase (eNOS); potassium voltage-gated channel subfamily J member 11 (KCNJ11); gene polymorphism.

Objectives: To determine ocular pathologies that appear in pregnant women with no history of ocular or systemic disease prior to conception. Study Design: Cross-sectional study. Setting: Department of Ophthalmology in association with Department of Gynecology, Pak Red Crescent Medical and Dental College Dina Nath District Kasur. Period: January 2018 to April 2018. Materials and Methods: One hundred and twenty pregnant females with no history of previous ocular or systemic co morbidity were included in study. After obtaining informed consent detailed ocular and medical history was taken and complete ocular examination was done. Results: Mean age of the participant female was 24.7 years (Range 19- 40 years). Four of them (3.33%) had bilateral optic disc edema, 2 of them had central serous chorioretinopathy (CSCR) and one female had unilateral macular hole. Conclusions: Ocular pathologies emerging in pregnancy are not uncommon and should not be overlooked. Pregnant women with ocular complaints should undergo a thorough ocular and systemic examination along with necessary investigations so that the pathological eye changes and associated systemic diseases could be managed timely and properly.

Background: Medical therapy is often prescribed to reduce the rate of aortic dilatation and prevent aortic dissection in patients with bicuspid aortic valve (BAV) despite a lack of evidence. We conducted an anonymous survey to gain insight into Canadian clinical practice regarding medical therapy used to slow the progression of aortic dilatation in patients with BAV. Methods: A questionnaire was sent to 115 paediatric cardiologists and 18 adult congenital heart disease specialists in Canada. Results: Ninety of 113 paediatric cardiologists (80%) completing the questionnaire reported prescribing medication to reduce the rate of aortic dilatation. Some 75% (61/81) of them reported prescribing medications on the basis of aortic size z scores, and 78% (48/61) considered medication at a z score between ≥ 2 and < 5. The remaining 25% of responders (20/81) reported prescribing medications on the basis of absolute aortic diameter, and 80% (16/20) of them considered initiating medical therapy at an aortic diameter > 40 mm to < 50 mm. For practical purposes, however, 40% of respondents (45/113) would not or rarely consider medical therapy for this indication because of variation in the threshold for initiating treatment. Ten of 14 adult congenital heart disease specialists’ responses (71%), reported prescribing medications who were excluded because of missing data. Conclusion: The majority of Canadian paediatric cardiologists reported prescribing medications to slow the rate of aortic dilatation in patients with BAV. However, there is heterogeneity in the criteria to prescribe medical therapy. A multicenter randomized controlled trial is needed to establish the role of medical therapy in this patient population. Résumé: Introduction: En dépit du manque de données probantes, un traitement médical est souvent prescrit pour réduire le taux de dilatation aortique et prévenir la dissection aortique chez les patients ayant une bicuspidie aortique (BA). Nous avons mené une enquête anonyme pour avoir un aperçu de la pratique clinique au Canada en ce qui concerne le traitement médical utilisé pour ralentir la progression de la dilatation aortique chez les patients ayant une BA. Méthodes: Nous avons envoyé un questionnaire à 115 cardiologues en pédiatrie et à 18 spécialistes en cardiopathie congénitale de l’adulte du Canada. Résultats: Quatre-vingt-dix des 113 cardiologues en pédiatrie (80 %) ayant rempli le questionnaire ont signalé prescrire des médicaments pour réduire le taux de dilatation aortique. Certains d’entre eux, soit 75 % (61/81) ont signalé prescrire des médicaments en fonction du Z-score de la taille aortique, et 78 % (48/61) ont envisagé de prescrire les médicaments lorsque le Z-score était entre ≥ 2 et < 5. Les 25 % de répondants restants (20/81) ont signalé prescrire des médicaments en fonction du diamètre aortique absolu, et 80 % (16/20) d’entre eux ont envisagé de faire commencer le traitement médical lorsque le diamètre aortique était entre > 40 mm et < 50 mm. Concrètement, toutefois, 40 % des répondants (45/113) n’ont pas envisagé ou ont rarement envisagé de prescrire un traitement médical pour cette indication en raison de la variation dans le seuil de mise en place du traitement. Dix des 14 réponses (71 %) des spécialistes de la cardiopathie congénitale de l’adulte ont signalé prescrire des médicaments qui étaient exclus en raison de données manquantes. Conclusion: La majorité des cardiologues en pédiatrie du Canada ont signalé prescrire des médicaments pour ralentir le taux de dilatation aortique chez les patients ayant une BA. Toutefois, les critères utilisés pour prescrire un traitement médical sont hétérogènes. Un essai clinique multicentrique et à répartition aléatoire est nécessaire pour déterminer le rôle du traitement médical dans cette population de patients.

PURPOSE/OBJECTIVE(S): Management of localized high-risk prostate cancer remains challenging. At our institution we performed a prospective Phase II study of 2 years of androgen deprivation therapy (ADT), pelvic radiation, Cesium (Cs)-131 brachytherapy boost, and adjuvant docetaxel in high risk, localized prostate cancer with a primary endpoint of 3-year disease-free survival. MATERIALS/METHODS: Acute/chronic hematologic, gastrointestinal (GI) and genitourinary (GU) toxicities were scored based on the CTCAE v3.0/RTOG-EORTC criteria, respectively. Actuarial biochemical recurrence free survival (bRFS), bRFSdisease free survival (DFS) and overall survival (OS) were calculated. Patients had a median age of 62 years (range 45–82), median Gleason score 8 (74% Gleason 8–10), median PSA of 11.2 (range 2.8–96), and 47% cT2-T3a stage disease. Androgen deprivation was given for two years, 45 Gy whole-pelvis IMRT was followed by an 85 Gy Cs-131 boost to the prostate gland, and adjuvant docetaxel was given for 4 cycles. RESULTS: Thirty eight patients enrolled from 2006–2014, with 82% completing protocol specified treatment, and 84.2% completing 4 cycles of docetaxel. Median follow-up for the entire and alive cohorts were 44 months and 58 months (range 3.4–118), respectively. Acute grade ≥ 2 GI and GU toxicity rates were 18.4% and 23.7%, respectively. Chronic grade ≥ 2 GI and GU toxicity rates were 2.6% and 2.6%, respectively. Twelve patients (31.6%) developed grade 4 hematologic toxicity, with no grade 5 toxicity. The 5-year DFS, bRFS and OS rates were 74.1%, 86.0% and 80.0%, respectively. CONCLUSION: This aggressive pilot multi-modal approach appears to be safe and well-tolerated, providing disease control in a significant proportion of patients with particularly high risk prostate cancer.

An overwhelming number of research articles have reported a strong relationship of the microbiome with cancer. Microbes have been observed more commonly in the body fluids like urine, stool, mucus of people with cancer compared to the healthy controls. The microbiota is responsible for both progression and suppression activities of various diseases. Thus, to maintain healthy human physiology, host and microbiota relationship should be in a balanced state. Any disturbance in this equilibrium, referred as microbiome dysbiosis becomes a prime cause for the human body to become more prone to immunodeficiency and cancer. It is well established that some of these microbes are the causative agents, whereas others may encourage the formation of tumours, but very little is known about how these microbial communications causing change at gene and epigenome level and trigger as well as encourage the tumour growth. Various studies have reported that microbes in the gut influence DNA methylation, DNA repair and DNA damage. The genes and pathways that are altered by gut microbes are also associated with cancer advancement, predominantly those implicated in cell growth and cell signalling pathways. This study exhaustively reviews the current research advancements in understanding of dysbiosis linked with colon, lung, ovarian, breast cancers and insights into the potential molecular targets of the microbiome promoting carcinogenesis, the epigenetic alterations of various potential targets by altered microbiota, as well as the role of various chemopreventive agents for timely prevention and customized treatment against various types of cancers.

PURPOSE Prostate cancer (PCa) becomes resistant to androgen ablation through adaptive upregulation of the androgen receptor in response to the low-testosterone microenvironment. Bipolar androgen therapy (BAT), defined as rapid cycling between high and low serum testosterone, disrupts this adaptive regulation in castration-resistant PCa (CRPC). METHODS The TRANSFORMER (Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance) study is a randomized study comparing monthly BAT (n = 94) with enzalutamide (n = 101). The primary end point was clinical or radiographic progression-free survival (PFS); crossover was permitted at progression. Secondary end points included overall survival (OS), prostate-specific antigen (PSA) and objective response rates, PFS from randomization through crossover (PFS2), safety, and quality of life (QoL). RESULTS The PFS was 5.7 months for both arms (hazard ratio [HR], 1.14; 95% CI, 0.83 to 1.55; P = .42). For BAT, 50% decline in PSA (PSA50) was 28.2% of patients versus 25.3% for enzalutamide. At crossover, PSA50 response occurred in 77.8% of patients crossing to enzalutamide and 23.4% to BAT. The PSA-PFS for enzalutamide increased from 3.8 months after abiraterone to 10.9 months after BAT. The PFS2 for BAT→enzalutamide was 28.2 versus 19.6 months for enzalutamide→BAT (HR, 0.44; 95% CI, 0.22 to 0.88; P = .02). OS was 32.9 months for BAT versus 29.0 months for enzalutamide (HR, 0.95; 95% CI, 0.66 to 1.39; P = .80). OS was 37.1 months for patients crossing from BAT to enzalutamide versus 30.2 months for the opposite sequence (HR, 0.68; 95% CI, 0.36 to 1.28; P = .225). BAT adverse events were primarily grade 1-2. Patient-reported QoL consistently favored BAT. CONCLUSION This randomized trial establishes meaningful clinical activity and safety of BAT and supports additional study to determine its optimal clinical integration. BAT can sensitize CRPC to subsequent antiandrogen therapy. Further study is required to confirm whether sequential therapy with BAT and enzalutamide can improve survival in men with CRPC.

Colorectal cancer (CRC), a disease of high incidence and mortality, has had few treatment advances owing to a large degree of inter- and intratumoral heterogeneity. Attempts to classify subtypes of colorectal cancer to develop treatment strategies has been attempted by Consensus Molecular Subtypes (CMS) classification. However, the cellular etiology of CMS classification is incompletely understood and controversial. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells from an independent CRC patient cohort. We describe subclonal transcriptomic heterogeneity of CRC tumor epithelial cells, as well as discrete stromal populations of cancer-associated fibroblasts (CAFs). Within CRC CAFs, we identify the transcriptional signature of specific subtypes (CAF-S1 and CAF-S4) in more than 1,500 CRC patients using bulk transcriptomic data that significantly stratifies overall survival in multiple independent cohorts. We also uncovered two CAF-S1 subpopulations, ecm-myCAF and TGFß-myCAF, known to be associated with primary resistance to immunotherapies. We demonstrate that scRNA analysis of malignant, stromal, and immune cells exhibit a more complex picture than portrayed by bulk transcriptomic-based Consensus Molecular Subtypes (CMS) classification. By demonstrating an abundant degree of heterogeneity amongst these cell types, our work shows that CRC is best represented in a transcriptomic continuum crossing traditional classification systems boundaries. Overall, this CRC cell map provides a framework to re-evaluate CRC tumor biology with implications for clinical trial design and therapeutic development.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3&prime, UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: &minus, 14.74 to &minus, 0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p &lt, 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%, GS 7 median = 85.8%, p-value = 9.4 &times, 10&minus, 4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.

Introduction : The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). Methods and Materials : Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations. Results : Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest in the clinical trial group (50.3 [35.8–not reached] months) versus pazopanib (39.0 [29.7–50.9] months) and sunitinib 26.2 [19.9–61.5] months). Non-clear cell RCC (21.5% of patients) was associated with worse median OS than clear cell RCC (18.0 vs 47.3 months). Differences in baseline characteristics, treatment starting dose, and relative dose exposure among treatment groups suggest selection bias. Survey results revealed a de-emphasis on quality of life, toxicity, and patient preference compared with efficacy in treatment selection. Conclusion : The MaRCC Registry gives insights into real-world first-line treatment selection, outcomes, and physician rationale regarding initial treatment selection prior to the immunotherapy era. Differences in outcomes between clinical trial and off-study patients reflect the difficulty in translating trial results to real-world patients, and emphasize the need to broaden clinical trial eligibility. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed regarding these endpoints. MicroAbstract : The Metastatic Renal Cell Carcinoma Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). 376 patients with mRCC and no prior systemic therapy were included in this study. This report describes initial real-world treatment patterns. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed.

We read with great interest the paper by Dong et al. ([1][1]) describing the clinical course of 4 patients with pre-existing heart failure infected by COVID-19. The authors convey the message that patients with cardiovascular disease are more prone to adverse outcomes due to direct inflammatory

To compare the effect of umbilical cord milking (UCM) vs. early cord clamping (ECC) on cerebral blood flow (CBF). Preterm infants

BackgroundOsteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment.MethodsWe searched peer-reviewed literature on the PubMed database using key words “androgen-deprivation therapy,” “androgen receptor inhibitors,” “bone,” “bone complications,” and “nonmetastatic prostate cancer” from 2000 to present.ResultsWe discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health.ConclusionsIn patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.

Background: Dermatophytosis is a growing menace these days. Dermoscopy is a simple and non invasivediagnostic technique used in dermatology. But there are few studies on dermoscopy of dermatophytosis.Objective: The present study aims to study thedermoscopic findings of dermatophytosis and to study itscorrelation with clinical and histopathological findings.Materials and Method: It was a cross sectional study done over a period of 3 months.100 patients with clinicaldiagnosis of any form of dermatophytosis, were included after taking an informed consent. Diagnosis ofdermatophytosis was made clinically followed by KOH examination. Clinical examination, photographsand dermoscopy was done in all cases. Dermoscopy was taken by hand held dermoscope (Dermlite 4 genDL4, California USA), with a magnification of 10x. Biopsy was done in selected patients.Results: Out of 100 patients, male-to-female ratio was 1.5:1. Mean age was 38 ± 8.7 years. Mean durationof disease was 3months. Tinea corporis was the most common type, followed by tinea cruris and tineafacie. Dermoscopic findings of tinea corporis, cruris and facie were -peripherally distributed white scales,red to grey background, red to brownish black dots and globules at periphery, follicular micropustues andperifollicular scales. Tinea capitis showed black dots, broken hair and Morse code hair. Onychomycosisshowed yellowish brown discoloration with subungual hyperkeratosis and jagging of free edge of nail plate.Conclusion: In absence of adequate lab facilities, dermoscopy acts as a complentary tool to clinicaldiagnosis. Dermoscopy helps to initiate early treatment, thus helping to reduce tinea menace.

Cancer stem cells (CSCs) contribute to disease progression and treatment failure in human cancers. The balance among self-renewal, differentiation, and senescence determines the expansion or progressive exhaustion of CSCs. Targeting these processes might lead to novel anticancer therapies. Here, we uncover a novel link between BRD4, mitochondrial dynamics, and self-renewal of prostate CSCs. Targeting BRD4 by genetic knockdown or chemical inhibitors blocked mitochondrial fission and caused CSC exhaustion and loss of tumorigenic capability. Depletion of CSCs occurred in multiple prostate cancer models, indicating a common vulnerability and dependency on mitochondrial dynamics. These effects depended on rewiring of the BRD4-driven transcription and repression of mitochondrial fission factor (Mff). Knockdown of Mff reproduced the effects of BRD4 inhibition, whereas ectopic Mff expression rescued prostate CSCs from exhaustion. This novel concept of targeting mitochondrial plasticity in CSCs through BRD4 inhibition provides a new paradigm for developing more effective treatment strategies for prostate cancer.

The switching of serotype from Ogawa to Inaba and back to Ogawa has been observed temporally in Vibrio cholerae O1, which is responsible for endemic cholera in Bangladesh. The serospecificity is key for effective intervention and for preventing cholera, a deadly disease that continues to cause significant morbidity and mortality worldwide. In the present study, WGS of V. cholerae allowed us to better understand the factors associated with the serotype switching events observed during 2015 to 2018. Genomic data analysis of strains isolated during this interval highlighted variations in the genes ctxB, tcpA, and rtxA and also identified significant differences in the genetic content of the mobilome, which included key elements such as SXT ICE, VSP-II, and PLE. Our results indicate that selective forces such as antibiotic resistance and phage resistance might contribute to the clonal expansion and predominance of a particular V. cholerae serotype responsible for an outbreak., The temporal switching of serotypes from serotype Ogawa to Inaba and back to Ogawa was identified in Vibrio cholerae O1, which was responsible for seasonal outbreaks of cholera in Dhaka during the period 2015 to 2018. In order to delineate the factors responsible for this serotype transition, we performed whole-genome sequencing (WGS) of V. cholerae O1 multidrug-resistant strains belonging to both the serotypes that were isolated during this interval where the emergence and subsequent reduction of the Inaba serotype occurred. The whole-genome-based phylogenetic analysis revealed clonal expansion of the Inaba isolates mainly responsible for the peaks of infection during 2016 to 2017 and that they might have evolved from the prevailing Ogawa strains in 2015 which coclustered with them. Furthermore, the wbeT gene in these Inaba serotype isolates was inactivated due to insertion of a transposable element at the same position signifying the clonal expansion. Also, V. cholerae isolates in the Inaba serotype dominant clade mainly contained classical ctxB allele and revealed differences in the genetic composition of Vibrio seventh pandemic island II (VSP-II) and the SXT integrative and conjugative element (SXT-ICE) compared to those of Ogawa serotype strains which remerged in 2018. The variable presence of phage-inducible chromosomal island-like element 1 (PLE1) was also noted in the isolates of the Inaba serotype dominant clade. The detailed genomic characterization of the sequenced isolates has shed light on the forces which could be responsible for the periodic changes in serotypes of V. cholerae and has also highlighted the need to analyze the mobilome in greater detail to obtain insights into the mechanisms behind serotype switching.

The androgen receptor (AR) pathway plays a central role in the development of castration-resistant prostate cancer (CRPC). The histone demethylase JMJD1A has been shown to regulate activities of AR and c-Myc transcription factors and promote prostate cancer progression. Here, we report that JMJD1A protein stability is controlled by the ubiquitin ligase STUB1. High levels of JMJD1A were strongly correlated with low STUB1 levels in human CRPC specimens. STUB1 inhibited AR activity, AR-V7 levels, and prostate cancer cell growth partly through degradation of JMJD1A. Furthermore, the acetyltransferase p300 acetylated JMJD1A at lysine (K) 421, a modification that recruits the BET family member BRD4 to block JMJD1A degradation and promote JMJD1A recruitment to AR targets. Increased levels of both total and K421-acetylated JMJD1A were observed in prostate cancer cells as they developed resistance to the AR antagonist enzalutamide. Treatment of prostate cancer cells with either p300 or BET inhibitors destabilized JMJD1A, and enzalutamide-resistant prostate cancer cells were more sensitive than parental cells to these inhibitors. Together, our findings identify a critical role for acetylation of JMJD1A in regulating JMJD1A stability and AR activity in CRPC. These newly identified mechanisms controlling JMJD1A protein stability provide potential druggable targets to encourage the development of additional therapies for advanced prostate cancer. Significance: Identification of mechanisms regulating JMJD1A protein stability reveals new strategies to destabilize JMJD1A and concomitantly inhibit AR activities as potential prostate cancer therapy.

Background: The role of the electrophysiologic studies in peripheral nerves and muscles of lower limbs (including paraspinal muscles) in prolapsed lumbar intervertebral discs has been studied with equivocal results. Pre- and post-operative electrodiagnostic studies have not been compared much. Aims and Objectives: To study the role of the electrophysiologic studies in prolapsed lumbar/lumbosacral intervertebral discs for finding the association between clinical findings and electrophysiological changes and to compare the electrophysiologic studies pre- and post-operatively. Materials and Methods: The study was conducted from July 2014 to June 2016 on fifty patients who were admitted in the department of neurological surgery with lumbar disc prolapse and all these patients were subjected to surgery. Both pre- and post-operative (from 1 to 6 months after surgery) electrophysiological studies were conducted and compared. Results: As per the electromyographic (EMG) abnormalities, the most common levels of intervertebral disc prolapse were L4–L5 and L5–S1 accounting for 32% of cases each followed by L5–S1 level which was seen in 28% of patients with L2–L3, L3–L4, and L4–L5 prolapsed intervertebral disc (PIVD) and L3–L4 and L4–L5 PIVD were seen in 4% of cases each. Of the 50 patients, EMG findings correlated with operative findings in 37 (74%) patients, however operative findings did not correlate with EMG findings in 13 (26%) patients. Conclusion: In compressive lesions of nerve roots (due to disc prolapsed), the EMG method has a high degree of accuracy in determining not only the presence of such lesions but also their exact location. EMG is accurate when correlated with the operative findings.

Introduction: Low backache (LBA) is highly prevalent in osteoporotic patients and affects their quality of life. Overall, osteoporosis incidence is greater in females than in males, and osteoporotic fractures typically occur with only modest or moderate trauma. Aims and Objectives: To evaluate osteoporosis as a cause of LBA in patients attending a neurosurgical outpatient department and to study various risk factors associated with it. Materials and Methods: The study entitled “Osteoporosis presenting as LBA: an entity not uncommon to be missed” was a 2-year hospital-based study conducted from August 2014 to July 2016 in a prospective manner and included 100 patients of osteoporosis with LBA. Analysis of records included their chief complaints, signs and symptoms, diagnostic investigations performed, treatment modalities they underwent, and further recommended management carried on them. Results: Out of total 100 patients evaluated, 33 (33%) were male and 67 (67%) were female; the age of patients was in the range of 35–70 years (mean 56.54 ± 91). The number of patients with a significant medical or surgical history was 31 (31%). The history of drug intake such as thyroxine, steroids, and antiepileptics was present in a total of 11 patients out of which 10 were female and one was male. Regarding lifestyle characteristics of studied patients, a total number of 72 (72%) were having sedentary habits with 15 (45.5%) males and 57 (85.1) females, the total number of moderate workers was 19 (27.3) males and 10 (14.9%) females, and heavy workers were 9 (9%) with 9 (27.3) males and 0 (0%) female. Conclusion: LBA is highly prevalent in osteoporotic patients especially in women. The incidence of osteoporosis and LBA increased with low body mass index, increasing age, and duration of menopause. The various risk factors for osteoporosis include smoking, history of medical diseases such as diabetes mellitus, history of hysterectomy, and history of antiepileptic, thyroxine, and steroid intake.

Next-generation Sequencing (NGS) of cancer tissues is increasingly being carried out to identify somatic genomic alterations that may guide physicians to make therapeutic decisions. However, a single tissue biopsy may not reflect complete genomic architecture due to the heterogeneous nature of tumors. Circulating tumor DNA (ctDNA) analysis is a robust noninvasive method to detect and monitor genomic alterations in blood in real time. We analyzed 28 matched tissue NGS and ctDNA from gastrointestinal and lung cancers for concordance of somatic genomic alterations, driver, and actionable alterations. Six patients (21%) had at least one concordant mutation between tissue and ctDNA sequencing. At the gene level, among all the mutations (n = 104) detected by tissue and blood sequencing, 7.7% (n = 8) of mutations were concordant. Tissue and ctDNA sequencing identified driver mutations in 60% and 64% of the tested samples, respectively. We found high discordance between tissue and ctDNA testing, especially with respect to the driver and actionable alterations. Both tissue and ctDNA NGS detected actionable alterations in 25% of patients. When somatic alterations identified by each test were combined, the total number of patients with actionable mutations increased to 32%. Our data show significant discordance between tissue NGS and ctDNA analysis. These results suggest tissue NGS and ctDNA NGS are complementary approaches rather than exclusive of each other. When performed in isolation, tissue and ctDNA NGS can each potentially miss driver and targetable alterations, suggesting that both approaches should be incorporated to enhance mutation detection rates. Larger prospective studies are needed to better clarify this emerging precision oncology landscape. Mol Cancer Ther; 17(5); 1123–32. ©2018 AACR.

Primary intracranial melanoma is an uncommon entity and only case reports have been published in the literature. We report a case of an elderly male who was operated with a preliminary diagnosis of meningioma, but it proved to be a histological surprise as it came out to be melanoma with no primary anywhere in the body.

Introduction: Traumatic brain injury (TBI) is a major cause of death and disability throughout the world. Commonly used predictors of outcome both individually or in combination include age, Glasgow Coma Scale score, pupillary reactivity, early hypoxia, and hypotension. Most of the studies previously done to examine risk factors for mortality in severe TBI were done in the setting of polytrauma. Aims and Objectives: The aim and objective of this study was to do an in-depth analysis of various factors associated with the management and outcome of patients with isolated TBI admitted in an Intensive Care Unit (ICU). Materials and Methods: A total of seventy adult patients who were admitted to Intensive Critical Care Unit (ICU) with isolated TBI were selected during a 12-month period from January 2016 to December 2016. This is a prospective analytical study and parameters studied included age, sex, cause of admission classified by type of trauma, premorbid functional status, acute and chronic comorbidities, brain noncontrast computed tomography scan data, Glasgow Coma Scale (GCS), hemodynamic status, respiratory status, and mechanical ventilation, blood gases, serum electrolytes, serum glucose, hemoglobin, leukocyte and platelet counts, renal function, and urinary output. Results: The study population consisted of 46 (65.7%) males and 24 (34.2%) females. The mean age was 35.5 years (range, 18–65 years). The most common mode of trauma was road traffic accident (43.6%) followed by fall from height (35.7%). Statistically insignificant relationship (P < 0.05) was seen with sex and mode of injury among survivors and nonsurvivors; however, 61.9% of patients with age ≥40 years died (P < 0.005). Among clinical parameters at admission to ICU, low GCS, hypotension (mean arterial pressure ≤80 mmHg), hypoxia (pO2 ≤60 mmHg, spO2 ≤90 mmHg), and nonreacting pupils were significantly associated with increased mortality (P < 0.05). Conclusion: Isolated TBI still continues to have a good amount of morbidity and mortality which perhaps can be reduced by strict adherence to guidelines of management.

Purpose/Objective(s) Prostatectomy (RP) is a treatment (tx) option even for high-risk prostate cancer (PC) per the NCCN guidelines. We report the long-term follow-up of a pilot clinical trial using an aggressive multimodal approach integrating chemo-hormone tx, prostatectomy (RP) and adjuvant radiation (RT) in men with high/very high-risk PC. Materials/Methods Preoperative tx entailed 6 months (mo) of chemo-hormones consisting of LHRH agonist (6 mo) integrated with adriamycin (A) and docetaxel (T). Two dose levels of A and T were incorporated with LHRH agonist tx: a higher dose (HD) of A (50mg/m2) and T (70mg/m2), and a lower dose (LD) of A (15mg/m2) and T (30mg/m2). HD chemo was given on 2 separate occasions (3 days post LHRH injection) in an effort to take advantage of the expected testosterone surge that occurs 3-5 days post LHRH agonist tx, while LD chemotherapy was given at other time points during the 6-month neoadjuvant period. This was followed by RP. The median post-op RT dose was 70.2 Gy (whole pelvis, with cone downs; range: 64.8-70.2) via 3D-CRT/IMRT. Three patients did not undergo RP after neoadjuvant chemo-hormone tx and went on to receive definitive RT (75.6 Gy). The overall survival (OS), disease-free survival (DFS), freedom from PSA failure (bNED, PSA > 0.2), and late GI/GU toxicity rates were calculated using the Kaplan-Meier method. Results A total of 22 men were enrolled from 2002-2006. Median pre-tx age, PSA and Gleason score were 61 years (range, 43-70), 24.1 ng/ml (range, 1.6-168.3) and 7 (range, 6-10), respectively. A total of 77% of patients received all therapy as planned. Median follow-up for the entire cohort and those alive were 10.9 years (range, 3.4-18.4) and 16.8 years (range, 15-18.4), respectively. The 15-year OS, DFS and bNED rates were 31.2%, 22.7% and 46.2%, respectively. Six patients (27%) never achieved PSA Conclusion Despite an aggressive multimodal regimen that incorporated chemo-hormones, RP and adjuvant RT for high/very high-risk prostate cancer, the 15-year bNED rate was only 46.5%. Therefore, the role of RP and neoadjuvant chemo-hormone therapy remains questionable among high-risk patients in light of superior long-term outcomes demonstrated in trials like ASCENDE-RT that incorporated brachytherapy boost with RT and androgen deprivation.

Tumor treating fields (TTFields) are among clinically active anticancer modalities that utilize low‐intensity, intermediate frequency (IF), and alternating electric fields (AEFs) to selectively disrupt mitosis in cancerous cells. Application of TTFields in the range of 100–900 kHz in cancer therapy and its effect on normal and cancer cells have attracted a great deal of interest in recent years. TTFields affect solid tumors by introducing increased chromatid aberrations that reduce the capacity to repair DNA damage and chromosome segregation, resulting in autophagy and subsequent cell death. In this review, we present an overview of the applications of TTFields in the treatment of cancer. We discuss several practical applications of TTField frequencies combined with metallic nanoparticles (NPs) (magnetic or nonmagnetic NPs) for internalization into cancer cells. In addition, TTFields can be combined effectively with chemotherapy and radiotherapy.

Although, cardiac injury, pneumothorax and pneumomediastinum are associated with COVID-19, differentiation of their symptoms and signs from those of COVID-19 itself is challenging. Without a high index of suspicion, cardiomyopathy and anterior pneumothorax are easily missed. These complications may be underdiagnosed in patients with COVID-19. Cardiomyopathy and pneumothorax may cause or exacerbate respiratory failure. If their management is delayed, cardiac arrest can occur. To increase the awareness of these issues, we describe the course and imaging of a 39-year-old woman with severe COVID-19 who developed cardiomyopathy and a small anterior pneumothorax with pneumomediastinum. Transthoracic echocardiography is technically challenging in the presence of anterior pneumothorax. Furthermore, although CT is the gold standard for the diagnosis of pneumothorax, this is not always feasible in critically ill patients. Lateral decubitus chest X-rays and lung ultrasound may facilitate the diagnosis of pneumothorax at the bedside of patients with COVID-19.

Background The European Association of Cardiology (ESC) Guidelines on the diagnosis and treatment of acute heart failure (AHF) indicate prompt therapy initiation and performance of relevant investigations as paramount. Specifically, echocardiography prior to treatment is advocated only with hemodynamic instability, and the evaluation of clinical signs of peripheral perfusion and congestion is suggested as guidance for early interventions. Given the growing body of evidence on the diagnostic/monitoring capabilities of bedside ultrasound (including focused cardiac ultrasound, comprehensive echocardiography, lung ultrasound), we discuss the potential benefit of an integrated clinical/ultrasound approach at the very early stages of acute heart failure. Methods and Results We proposed a narrative review of the current evidence on the clinical-ultrasound integrated approach to AHF, with special emphasis on the components of the early diagnostic-therapeutic workup where cardiac, inferior vena cava and lung ultrasound showed high diagnostic accuracy and the capability of substantially changing an exclusively clinically-oriented patient management. A proactive comment to the ESC guidelines is made, suggesting an integration of clinical and biochemical assessment, as defined by guidelines, with combined bedside ultrasound on may help in the definition of AHF pathophysiology and treatment. Conclusion A multi-organ integrated clinical-ultrasound approach should be advocated as part of the clinical-diagnostic workup at AHF very early phase. Whenever competence and technology available, bedside ultrasound, along with clinical and biochemical assessment, should target AHF profiling, identify the cause of AHF, and subsequently aid disease course and response to treatment monitoring.

The current overview will summarize some of the developments in the area of protein translation, including their relation to the therapeutic targeting of prostate cancer.Translational control, mediated by the rate-limiting eukaryotic translation initiation factor 4E (eIF4E), drives selective translation of several oncogenic proteins, thereby contributing to tumor growth, metastasis, and treatment resistance in various cancers, including prostate cancer. As an essential regulatory hub, several oncogenic hyperactive signaling pathways appear to converge on eIF4E to promote tumorigenesis. Several approaches that target the eIF4E-dependent protein translation network are being actively studied, and it is likely that some may ultimately emerge as promising anticancer therapeutics.An array of inhibitors has shown promise in targeting specific components of the translational machinery in several preclinical models of prostate cancer. It is hoped that some of these approaches may ultimately have relevance in improving the clinical outcomes of patients with advanced prostate cancer.

Myricetin, one of the most extensively studied polyphenols, is present abundantly in various fruits and vegetables and exhibits diverse pharmacological properties. The multifaceted biological action of myricetin against tumor heterogeneity makes it an impressive anticancer agent whose efficacy has been confirmed by an overwhelming number of studies. Myricetin shows its therapeutic potential by targeting and modulating the expression of various molecular target which are involved in inflammation, cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. Myricetin deters tumor progression by inducing apoptosis via both intrinsic and extrinsic pathway, activating/inactivating several signaling pathways, and reactivating various tumor suppressor genes. This comprehensive review represents the effect of myricetin on various hallmarks of cancer with insight into the molecular mechanism employed by myricetin to mitigate cell proliferation, angiogenesis, metastasis, and induce apoptosis. In addition, enhanced bioavailability of myricetin through conjugation and its increased efficacy as an anticancer agent when used in combination are also highlighted.

Background: The negative side effects of chemotherapeutic drugs have led to the need to identify safer therapeutics. A wide array of epidemiological and experimental data encourages the use of dietary agents to impede or delay different stages of cancer. Well tolerated lower doses of individual agents can be effectively employed if there is therapeutic synergy; thereby minimizing the side effects and enhancing successful outcome. However, a variety of interactions are possible when different agents are used in combination, therefore, dietary agents alone or in combination with chemotherapeutic agents must be thoroughly studied before considering them for clinical settings. Objectives: This study was designed to determine the interaction of two phytochemicals (quercetin, sulforaphane) with each other as well as with established chemotherapeutic drugs, like cisplatin and 5-fluorouracil. Methods: Cell viability assay, cell cycle analysis, and scratch wound assay were performed to understand their combined impact on proliferation and metastasis of HeLa cells. Further, combination index (CI) was calculated to identify the type of interaction between the tested compounds concurrently. Results: Concurrent administration of sublethal doses of the phytochemicals with chemotherapeutic drugs resulted in augmented anti-proliferative potential evidenced in elevated cytotoxicity, apoptosis induction, and inhibition of migration. Combination index was < 1 and indicated synergy between the tested compounds. Conclusions: Combination of these compounds can help to develop cancer treatment better.

PURPOSE OF REVIEW: This overview examines the rationale for dietary interventions for prostate cancer by summarizing the current evidence base and biological mechanisms for the involvement of diet in disease incidence and progression. RECENT FINDINGS: Recent data have further solidified the association between insulin resistance and prostate cancer with the homeostatic model assessment of insulin resistance (HOMA-IR). Data also show that peri-prostatic adipocytes promote extracapsular extension of prostate cancer through chemokines, thereby providing a mechanistic explanation for the association observed between obesity and high grade cancer. Regarding therapeutics, hyperinsulinemia may be the cause of resistance to PI3K inhibitors in the treatment of prostate cancer, leading to new investigations combining these drugs with ketogenic diets. SUMMARY: Given the recently available data regarding insulin resistance and adipokine influence on prostate cancer, dietary strategies targeting metabolic syndrome, diabetes and obesity should be further explored. In macronutrient-focused therapies, low carbohydrate/ketogenic diets should be favored in such interventions due to their superior impact on weight loss and metabolic parameters and encouraging clinical data. Other nutrients, including the carotenoid lycopene which is found in highest concentrations in tomatoes, may also play a role in prostate cancer prevention and prognosis through complementary metabolic mechanisms. The interplay between genetics, diet and prostate cancer is an area of emerging focus that might help optimize therapeutic dietary response in the future through personalization.

Bone metastases are a frequent complication of solid tumors, leading to significant skeletal sequelae that negatively impact quality of life and survival. Prevention and management of skeletal-related complications are critical treatment goals in oncology. Endpoints used in clinical trials to evaluate skeletal-related complications have evolved. In contrast to single measures of bone health, contemporary clinical trial endpoints reflect composite measures of skeletal-related complications, and increasingly also survival. In addition, key symptomatic components, which are more reflective of quality of life and the patient experience, are being incorporated. Given the evolution and resulting diversity of the endpoints being used in pivotal trials, it is becoming increasingly relevant to clarify the utility and the potential clinical impact of these measures not only within the context of trials but also in the real-world setting. Here, we describe the development and evolution of skeletal endpoints used in trials, and discuss their clinical relevance.

Introduction: Endoscopoic third ventriculostomy (ETV) is currently considered the best alternative to cerebrospinal fluid (CSF) shunt systems in the treatment of obstructive hydrocephalus. The aim of ETV is to communicate the third ventricle with the interpendicular cistern and create CSF flow which bypasses an obstruction to the circulation of the CSF. Aims and Objectives: The purpose of this study was to elucidate the indications, efficacy, safety and outcome Of ETV pediatric patients of noncommunicating hydrocephalus. Material and Methods: This study is a 3 year prospective study from June 2012 to May 2015. Records were kept for age, gender, etilogical factors, symptoms, signs, previous use of shunt or external ventricular device, imaging findings, and surgical complications (intraoperative and postoperative). Only those patients with age between 6months and 18 years with symptoms of intracranial hypertension and radiographic evidence of noncommunicating hydrocephalus were included in the study. Results: A total of 53 patients were studied, out of these 29 were boys and 24 were girls. The mean age of the patients was 6.6 years. Overall a total of 50 successful ETVs were done in 53 patients. The success rate is estimated to be 94%. There was no mortality. The average postoperative hospital stay was 4 days. The followup ranged from 6 to 16 months (mean, 12 months). Conclusion: ETV in children is a safe, simple and effective treatment and a logical alternative to shunting procedure for patients of noncommunicating hydrocephalus.