Multiple Therapeutic Regimens Research Articles

Changing Trends in B-Cell Non-Hodgkin Lymphoma Treatment: The Role of Novel Monoclonal Antibodies in Clinical Practice.

We are currently witnessing a dramatic shift in our approach to the treatment of B-cell non-Hodgkin lymphoma (B-NHL). In the evolving clinical landscape, novel treatments for this clinically heterogeneous disease span a wide range of interventions, encompassing targeted agents, cell therapy approaches, and novel monoclonal antibodies (NMABs). Among these, the latter are likely to exert the most profound impact due to their distinctive high efficacy and versatile applicability. NMABs represent a heterogeneous group of agents, including naked antibodies, immunotoxins, and T-cell-engaging molecules. In recent times, several NMABs have either gained regulatory approval or are on the verge of introduction into clinical practice, addressing multiple therapeutic indications and treatment regimens. Their anticipated impact is expected to be broad, initially in the context of relapsed/refractory (R/R) disease and subsequently extending to early treatment lines. The scope of this review is to provide a comprehensive overview of the biological characteristics, clinical properties, efficacy, and toxicity profiles of NMABs that have recently been introduced or are nearing integration into clinical practice.

Cost-effective Analysis of Prescribed Oral Hypoglycemic Agents amongst Pre-obese and Obese Diabetic Patients in a Tertiary Care Hospital in Odisha

Objectives: Diabetes is more prevalent in middle- and higher-income groups and is spreading at an alarming rate. Drug therapy is compulsory because of the chronic and progressive nature of the disease. With such multifactorial background of high prevalence, progressive nature of the disease leading to various complications, increased healthcare cost, and availability of multiple therapeutic regimens prescribed, this study has been done to evaluate the cost-effective analysis of oral hypoglycemic agents. Materials and Methods: This is a prospective, parallel group, and comparative observational study conducted by the Department of Pharmacology in collaboration with the Department of Endocrinology at Kalinga Institute of Medical Sciences, Bhubaneswar. The duration of the study was of 2 years. A total number of 220 patients were selected and based on body mass index, patients were categorized into preobese (new and old diabetic patients) and obese (new and old diabetic patients) categories. In this study, cost-effectiveness analysis (CEA) was done to evaluate the cost differences between two or more medication groups, with a similar clinical effect. Results of CEA are expressed as an average cost-effectiveness ratio or as an incremental cost-effectiveness ratio. Results: From this study, it is observed that in terms of benefit, dual therapy of Metformin and Dapagliflozin was most efficacious followed by Metformin and Sitagliptin as well as Metformin and Glimepiride combinations. If cost is considered, Metformin montherapy and metformin and Glimepiride dual therapy was most cost-effective. In triple regimen, MET+VOG+GLIM combination was seen to be more cost effective than gliptin combination, both in terms of control of FBS as well as PPBS. The cost of treatment goes parallel with duration of disease, being higher in the old cases of long-standing duration. Conclusion: The present study shows that SGLT2 inhibitors are better class of oral hypoglycemics in terms of long-term benefits and this group is prescribed as dual therapy more frequently but cost of therapy is the greatest barrier. Metformin and Sulfonylureas remain the most beneficial combination, both in terms of efficacy and cost. The cost of treatment was varying, depending on the duration of disease, being higher in old cases and lower in new cases.

Cytomegalovirus infection in patients with malignant lymphomas who have not received hematopoietic stem cell transplantation

BackgroundLife-threatening cytomegalovirus infection (CMVI) has been reported even in patients with malignant lymphoma (ML) who have not received hematopoietic stem cell transplantation (w/o HSCT) but had been treated with chemotherapy or radiotherapy. However, the CMVI incidence and risk factors (RFs) in patients with ML w/o HSCT have not been fully elucidated. This study aimed to evaluate the clinical aspects, including incidence and RFs, of CMVI in patients with ML w/o HSCT.MethodsWe retrospectively reviewed all patients with ML who received chemotherapy or radiotherapy in our department from 2005 to 2013. The overall survival (OS), incidence and RFs of CMVI, and other characteristics of patients with CMVI were analyzed.ResultsOverall, 236 patients with ML w/o HSCT were evaluated. Of these, 5.5% (13/236) developed CMVI; 54% (7/13) received steroid pretreatment before primary therapy (PT) for ML; and 62% (8/13) received > 2 therapeutic regimens for ML. The OS curve of patients with CMVI was significantly worse than that of patients without CMVI (p < 0.0001, log-rank test). A univariate analysis identified B symptoms (p = 0.00321), serum albumin < 3.5 g/dL (p = 0.0007837), C-reactive protein level > the upper limit of normal (p = 0.0006962), steroid pretreatment before PT for ML (p = 0.0004262), > 2 therapeutic regimens for ML (p = 0.0000818), T cell lymphoma (p = 0.006406), and non-complete remission (p = 0.02311) as RFs for CMVI. A multivariate analysis identified steroid pretreatment before PT for ML [odds ratio (OR): 4.71 (95% confidence interval [CI]: 1.06–21.0); p = 0.0419] and > 2 therapeutic regimens for ML [OR: 9.25 (95% CI: 2.33–36.8); p = 0.00159] as independent RFs for CMVI in patients with ML w/o HSCT.ConclusionsAttention should be paid to CMVI development in patients with ML w/o HSCT pretreated with steroids or who had multiple therapeutic regimens.

Early localized vitiligo, a medical emergency: Long-term follow-up study.

In spite of multiple therapeutic regimens for vitiligo, disease relapse remains a challenge. Most guidelines consider systemic treatments only in rapidly progressive disease with wider surface areas. This delay in halting the immune attack, may give the chance for further disease progression as well as establishment of resident memory T-cell population predisposing to future relapses. To assess the ability of early systemic therapy of localized (<2% BSA), recent onset (<6 months) vitiligo to control disease activity and minimize the possibility of recurrence. Twenty-five patients with recent onset (<6 months), localized (<2% BSA) vitiligo were included. Patients received pulse dexamethasone therapy for 6 months plus topical treatments and NB-UVB sessions. Patients were followed monthly as regards percent of repigmentation and VIDA score. To detect recurrence, biannual assessment was done for 4 years. Eighty-four percent of patients had acrofacial lesions and 44% had facial lesions. Arrest of activity was achieved after 3.65 ± 2.19 months. Complete repigmentation was achieved in a mean duration of 6.88 ± 0.2 months. At the end of the 4-year follow up, recurrence occurred in 32% of patients. In spite of recurrence, localized disease (<2% BSA) was secured. A significantly higher incidence of recurrence was associated with cases with bilateral distribution of lesions. Early systemic immunomodulation for recent localized vitiligo is a successful approach to achieve early control of disease activity and minimize the incidence of recurrence. Such cases should not be overlooked but managed as early as possible; it is a race against time.

The role of fenofibrate in the treatment of COVID-19

In December 2019, a severe pneumonia-like illness emerged in the city of Wuhan, China which inevitably led to the Coronavirus disease-19 (COVID-19) pandemic caused by the SARS-CoV-2 virus. Due to the increase in infectivity and mortality caused by the virus, multiple therapeutic regimens are being suggested in order to help tackle this problem. The infectivity of SARS-CoV2 virus is due to its ability to attach itself to the ACE II receptors on the host cells via its viral spike protein (S protein) and inducing its entry into the target cell. The effects of the drug, Fenofibrate on the ACE II receptors and also, how the pharmaceutical properties of this drug can help prevent viral entry and eventually, reduce severity in COVID-19 patients. Since this drug has a good profile and is relatively safe to use, the risk-to-benefit analysis is positive and can be beneficial for patients infected with severe SARS-CoV2 infection.

Stimuli-Sheddable Nanomedicine Overcoming Pathophysiological Barriers for Potentiating Immunotherapy of Cancer.

Immunotherapy displays potent potential for clinical cancer management by activating the protective immune response; however, the microenvironment of the immunosuppressive tumor restricts the efficiency of immunotherapies. Along with the complex pathophysiological barrier of the solid tumors, successful immunotherapeutic delivery remains a formidable challenge for conventional nanomedicine. Stimuli-sheddable nano vectors may facilitate the delivery of cargoes to tumors with minimal premature cargo leakage in blood circulation while enhancing the tumor penetration of nanomedicines by deshielding the polyethylene glycol (PEG) corona upon endogenous activity such as acidity, enzymes and glutathione, or external stimuli, such as laser irradiation. Throughout this study, researchers overviewed the recent advances of nanomedicine-based cancer immunotherapy using the stimuli-responsive deshielding nano vectors, which allowed researchers to integrate multiple therapeutic regimens for inducing immunogenic cell death. This aided in blocking the immune checkpoints, repolarizing the macrophages, and regulating the kynurenine metabolism. Furthermore, researchers discussed the critical issues in the development of stimuli-sheddable nanoimmunodulators, primarily aimed at speeding up their clinical translation. Finally, researchers provided novel perspectives for improving cancer management with the stimuli-sheddable nanomedicine.

Endogenous Stimuli‐Activatable Nanomedicine for Immune Theranostics for Cancer

AbstractCancer immunotherapy has witnessed significant advances in the past decade, however challenges associated with immune‐related adverse effects and immunosuppressive tumor microenvironment, have hindered their clinical application. Stimuli‐activatable nanomedicines hold great potential for improving the efficiency of cancer immunotherapy and minimizing the side effects via tumor‐specific accumulation, controllable drug release profile, and combinational therapy by integrating multiple therapeutic regimens. In this review, the recent advances of stimuli‐activatable nanomedicines for cancer immunotherapy are first described, with particular focus on endogenous stimuli including pH, glutathione, reactive oxygen species, and excessive enzymes within the tumor microenvironment. Then, the endogenous stimuli‐activatable nanomedicines that target tumor cells, immune cells, or periphery immune systems for eliciting sustained systemic immune activation and modulating the immunosuppressive tumor microenvironment, are described. Next, the general mechanisms underlying nanomedicine‐based immunotherapy by eliciting anti‐tumor immune responses and overcoming immunologic tolerance are described. Further, the emerging application of bioimaging techniques for monitoring immune response and evaluating therapy performance is described. Finally, the authors’ perspectives are provided for the clinical translation of nanomedicine‐based cancer immunotherapy.

S1426 Double Trouble: Chronic Pancreatitis and an Overlooked Superior Mesenteric Vein Thrombosis

INTRODUCTION: Chronic pancreatitis is a challenging disease process to manage. Abdominal pain is the most common, debilitating symptom for these patients. Here, we outline the outpatient approach and management of a patient with chronic pancreatitis who also had concomitant mesenteric venous thrombosis. CASE DESCRIPTION\METHODS: A 56-year-old man with history of tonsillar squamous cell carcinoma and non-small cell lung cancer treated with radiation, coronary artery disease, heavy tobacco use, cholecystectomy, and chronic pancreatitis complicated by pseudocysts and exocrine insufficiency presented to internal medicine clinic with persistent epigastric pain. Three years ago, he was diagnosed with chronic pancreatitis, secondary to heavy alcohol and tobacco use. In the interim, he quit alcohol, reduced smoking, and went through multiple therapeutic regimens including gabapentin, opioids, pancreatic enzyme replacement, and celiac plexus block. On exam, he was hemodynamically stable but in discomfort due to pain. He was cachectic and had epigastric tenderness without rebound tenderness or guarding. Laboratory tests revealed cholestatic transaminitis. We referred him to a gastroenterologist. MRCP showed irregular contour of the pancreas with smooth narrowing in the pancreatic neck concerning for a stricture. EGD and EUS were planned. Duloxetine was added to his regimen. However, MRI revealed an occlusion of the superior mesenteric vein at the level of the portal confluence with multiple collateral vessels at the root of the mesentery. Prior CT scan showed the presence of thrombus two years ago. Medical record did not reveal any management of the thrombus and the patient was unaware of the condition. He did not have evidence of portal hypertension. Given the severity of the symptoms and lack of prior anticoagulation, we started him on rivaroxaban. Despite this intervention, he continued to have flares of chronic pancreatitis in the subsequent months and will undergo another celiac plexus block. DISCUSSION: Chronic mesenteric venous thrombosis is often an incidental finding on imaging and usually asymptomatic. This is mainly considered a consequence of venous stasis and endothelial injury, compounded by risk factors such as local inflammation (e.g., pancreatitis), abdominal tumors or pseudocysts, and acquired thrombophilia. Anticoagulation is generally recommended. In the absence of predisposing illness or a hypercoagulable state, further work-up for portal hypertension and referral to hematology are indicated.

A practical approach to switch from a multiple pill therapeutic strategy to a polypill-based strategy for cardiovascular prevention in patients with hypertension.

: Pharmacological treatment recommended by guidelines for very high-risk patients with established cardiovascular disease (CVD) includes lipid-lowering drugs, antihypertensive agents and antiplatelet therapy. Depending on the associated comorbidities, this baseline regimen has to be complemented with other drugs. Therefore, the number of pills to be taken is usually high and adherence to these multiple pill therapeutic regimens and long-term persistence on treatment is low, being the main factor for insufficient control of cardiovascular risk factors. The CNIC (Centro Nacional de Investigaciones Cardiovasculares, Ministerio de Ciencia e Innovación, España) polypill is the only polypill containing low-dose aspirin approved by the EMA and marketed in Europe, and has demonstrated to improve adherence. For this reason, guidelines recommend its use for secondary prevention of CVD, and also for primary prevention of cardiovascular events in patients with multiple cardiovascular risk factors and advanced atherosclerotic process at high risk of thrombosis and low risk of bleeding. This article pretends to simplify the steps that clinicians may follow to switch from any baseline regimen to the polypill with the use of several algorithms and tables showing the equivalent effective daily doses of different angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins to facilitate switching, as well as the steps to be followed depending of the initial levels of BP and LDL-cholesterol values to achieve BP and lipid control with the association to the polypill of other BP-lowering or lipid-lowering drugs whenever needed.

Alcoholic and Non-Alcoholic Liver Diseases: Promising Molecular Drug Targets and their Clinical Development.

Alcoholic and non-alcoholic fatty liver diseases have become a serious concern worldwide. Both these liver diseases have an identical pathology, starting from simple steatosis to cirrhosis and, ultimately to hepatocellular carcinoma. Treatment options for alcoholic liver disease (ALD) are still the same as they were 50 years ago which include corticosteroids, pentoxifylline, antioxidants, nutritional support and abstinence; and for non-alcoholic fatty liver disease (NAFLD), weight loss, insulin sensitizers, lipid-lowering agents and anti-oxidants are the only treatment options. Despite broad research in understanding the disease pathophysiology, limited treatments are available for clinical use. Some therapeutic strategies based on targeting a specific molecule have been developed to lessen the consequences of disease and are under clinical investigation. Therefore, focus on multiple molecular targets will help develop an efficient therapeutic strategy. This review comprises a brief overview of the pathogenesis of ALD and NAFLD; recent molecular drug targets explored for ALD and NAFLD that may prove to be effective for multiple therapeutic regimens and also the clinical status of these promising drug targets for liver diseases.

Prescribing Pattern of Antidiabetic Drugs Amongst Pre-Obese Diabetic Patients in a Tertiary Care Hospital- An Observational Study

Background: In order to improve the prescription quality and rational prescription pattern promotion there is an inevitable need to investigate the factors that affect doctors' prescription patterns. Diabetes is a common non communicable disease. It leads to high morbidity and mortality due to the disease itself and its diverse complications like CAD, hypertension, renal complication, retinal damage, neurological disorders, generalised infections etc. With such multifactorial background of high prevalence, progressive nature of the disease, availability of multiple therapeutic regimens prescribed on trial and error basis, the treatment is individualized and neither complete nor satisfactory. Objectives: This study was undertaken to analyse the current prescribing pattern in pre-obese patients of type 2 diabetes mellitus with regard to drug/drugs precription, dose, and duration of treatment and frequency of change of drugs. Methods: This is a prospective, parallel group, comparitive observational study. The enrolled pre-obese patients were divided as a) New diabetic b) Old diabetic (&lt;3 years duration). Each category was further divided into four subgroups according to the treatment recieved a)Monotherapy-Metforminb)Combination therapy-Metformin+another antidiabetic groups, preferably sulfonylureas, alphaglucosidase inhibitors or DPP 4 inhibitors c)Triple therapy( Metformin+SU+Voglibose or Gliptins or Glitazones) d)Insulin with other oral hypoglycemic drugs. Results: In the study of prescribing pattern, it was observed that most prescriptions in this tertiary care hospital were found to be in compliance with the ADA guidelines. Metformin monotherapy was prescribed as initial treatment. Sulphonylureas/Gliptins/Alpha glucosidase inhibitors/thiazolidinediones were used as second line therapy mostly anyone, in addition to metformin or as monotherapy according to patient requirement, tolerability and cost.Conclusions: The antidiabetic medications prescribed in this hospital, were found to be in compliance with ADA guidelines

Corticotherapy vs. corticotherapy plus immunosuppressive therapy in acute Vogt-Koyanagi-Harada disease

Abstract Introduction Vogt-Koyanagi-Harada disease is a multisystem disorder characterized by a bilateral granulomatous panuveitis. Multiple therapeutic regimens have been used to control inflammation in acute uveitic stage to prevent irreversible visual loss. The purpose of this paper is to compare the effect, on functional and anatomic outcomes, of early treatment with standard corticotherapy vs. corticotherapy plus immunosuppressive (IMT) therapy in acute Vogt-Koyanagi-Harada disease (Group A vs. Group B). Methods A retrospective chart review of patients with Vogt-Koyanagi-Harada disease, with an evolution time of 2 weeks or less, who attended the Inflammatory Eye Disease Clinic, from 2001 to 2015. Data collected included demographic information, presenting features, treatment and improvement in visual acuity (VA). Results Sixteen charts were reviewed; 15 females (93.75%). Mean age: 30.81 ± 10.53 years, follow-up time (months): 54.94 ± 43.43. Ten patients (66.6%) had IMT, azathioprine, methotrexate and cyclophosphamide. In group A, initial VA Anterior chamber recurrences occurred in both groups and posterior pole recurrences were observed in group A. Time to first recurrence was similar (P Frequency of recurrence was 2.33 ± 1.80 vs. 1.5 ± 0.79 (P Conclusions Adding IMT as first line therapy to corticosteroids, do not matter significantly in terms of final VA or development of visually significant complications. In the IMT plus corticosteroids group number of recurrences was significantly lower, and a steroid sparing effect was evident.

Importance of hypersensitivity in adverse reactions to drugs in the elderly

BackgroundThe use of drugs in the elderly is very extensive because of the frequent occurrence of chronic diseases. Adverse drug reactions (ADRs) commonly occur in geriatric patients receiving multiple therapeutic regimens. In the literature, little attention has been given to ADRs in the elderly, and particularly to allergic reactions.ObjectiveThe aim of the present study is to provide data on possible inappropriate prescriptions in the elderly in relation to allergic reactions and to identify a list of drugs which are likely inducers of allergic reactions.MethodsWe retrospectively evaluated ADRs in patients referring to Immunoallergy Unit of Hospital Policlinico in Bari on the basis of Beers criteria. Among adverse reactions, hypersensitivity reactions were extracted and a comparison between different age groups was assessed.ResultsOut of 823 patients with ADRs, in 30.6% hypersensitivity drug reactions (HDR) were diagnosed. Data about drug intake, comorbidities and clinical presentation were collected, aiming to identify possible risk factors. An evaluation of drugs most commonly involved was assessed.ConclusionsHDR are reported to represent 5–10% of all ADRs, while in our study population the prevalence was about 30%. This suggests the need to develop strategies to minimize the incidence of drug allergy in the elderly, as well to reduce the phenomenon of inappropriate prescriptions.

Corticoterapia vs. corticoterapia con inmunosupresores en el tratamiento de la fase aguda del síndrome de Vogt-Koyanagi-Harada

IntroductionVogt-Koyanagi-Harada disease is a multisystem disorder characterized by a bilateral granulomatous panuveitis. Multiple therapeutic regimens have been used to control inflammation in acute uveitic stage to prevent irreversible visual loss. The purpose of this paper is to compare the effect, on functional and anatomic outcomes, of early treatment with standard corticotherapy vs. corticotherapy plus immunosuppressive (IMT) therapy in acute Vogt-Koyanagi-Harada disease (Group A vs Group B). MethodsA retrospective chart review of patients with Vogt-Koyanagi-Harada disease, with an evolution time of 2 weeks or less, who attended the Inflammatory Eye Disease Clinic, from 2001 to 2015. Data collected included demographic information, presenting features, treatment and improvement in visual acuity (VA). ResultsSixteen charts were reviewed; 15 females (93.75%). Mean age: 30.81±10.53 years, follow-up time (months): 54.94±43.43. Ten patients (66.6%) had IMT, azathioprine, methotrexate and cyclophosphamide.In group A, initial VA<20/200 in 66.7%; final VA was ≥20/40 in 9 eyes (75%). In group B, initial VA<20/200 in 65%; final VA≥20/40 in 15 eyes (75%). In group A, VA improved faster at one and 3 months (ANOVA P<.057). Clinical characteristics in convalescent stage and complications were similar.Anterior chamber recurrences occurred in both groups and posterior pole recurrences were observed in group A. Time to first recurrence was similar (P<.279).Frequency of recurrence was 2.33±1.80 vs 1.5±0.79 (P<.01). At recurrence 15 patients were still having oral steroids, nine in group A, 6 in Group B. In group A, prednisone was given during more time: mean 15.17±12.08 months, and time to reach to 10mg dose was longer: 8.60±11.7 (P<.008 and P<.046). ConclusionsAdding IMT as first line therapy to corticosteroids, do not matter significantly in terms of final VA or development of visually significant complications. In the IMT plus corticosteroids group number of recurrences was significantly lower, and a steroid sparing effect was evident.

Analysis of Therapeutic Outcome of Antidiabetic Medications in a Tertiary Care Hospital - An Observational Study

Background: Diabetes at present appears as a common non communicable disease. It leads to high morbidity and mortality due to the disease itself and its diverse complications like coronary artery disease, hypertension, renal complication, retinal damage, neurological disorders, incidence of stroke at different sites, generalized infections etc. With such multifactorial background of high prevalence , progressive nature of the disease leading to various complications and increase health care cost, availability of multiple therapeutic regimens prescribed on trial and error basis, the treatment is individualized and neither complete nor satisfactory. This study was undertaken to analyze the effect of antidiabetic medications on prognosis of the disease i.e. on glycemic status, lipid profile and on existing co-morbid conditions like hypertension and complications. Methods: This is a prospective, parallel group, comparative observational study. The enrolled patients were then divided as -Pre obese- categorized into a)New diabetic b)Old diabetic (<3 years duration). Obese similarly divided to a)New diabetic b)Old diabetic (<3 years duration). Each category was further divided into four subgroups according to the treatment received a)Monotherapy-only Metformin b)Combination therapy- Metformin another antidiabetic groups, preferably sulfonylureas, alphaglucosidase inhibitors or DPP 4 inhibitors c)Triple therapy (Metformin+SU +Voglibose or Gliptins or Glitazones) d)Insulin with other oral hypoglycemic drugs. Results: In primary outcome, reduction in all glycemic parameters were significant and progressive in both old and new diabetic cases at all follow up visits, both in preobese and obese groups. Analysis of secondary outcome revealed significant reduction in SBP, DBP and ACR in all the four groups while only LDL and Cholesterol were significantly reduced in all preobese and obese groups. Conclusions: The antidiabetic medications prescribed in this hospital, were effective in improving the glycemic status, blood pressure, lipid profile and renal status of all patients under the study.

Characteristics of 10-year survivors of high-grade serous ovarian carcinoma

Objectives: High-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor overall survival. However, the clinical features of long-term (LT; >10 years) survivors have not been well characterized. Methods: A multicenter research consortium was established among 5 participating academic centers in the United States. Patient selection criteria included a diagnosis of stage III/IV high-grade serous ovarian, fallopian tube, or primary peritoneal carcinoma with at least 10 years of follow-up from the date of initial diagnosis. Nonserous, borderline tumors and low-grade serous subtypes were excluded. Results: A total of 203 LT survivors with HGSC were identified. Median age at diagnosis was 57 years (range 37–84 years). Most patients had stage IIIC (72.4%) disease at presentation. Of those who underwent primary cytoreductive surgery, optimal cytoreduction (residual disease of no more than 1 cm in maximal diameter) was achieved in 143 (85.6%) patients, and 46.6% of all patients had a complete gross resection. After a median follow-up of 144 months, 88 (46.8%) patients did not develop recurrent disease. Twenty-one patients (11.2%) had 1 recurrence during the follow-up interval, 19 patients (10.1%) had 2 recurrences, and 60 patients (31.9%) had more than 2 recurrences. Of the 79 patients tested for BRCA1 and BRCA2 germline mutations, 43 (54.4%) carried a deleterious mutation. Of note, 24 (14%) patients had suboptimal cytoreductive surgery, 16 (11%) had a platinum-free interval of less than 12 months, and 100 (53%) with recurrent disease were surviving 10 or more years after diagnosis. Conclusions: Long-term survivors of advanced HGSC generally have clinical features including optimal surgical cytoreduction and platinum-sensitive disease. The majority of these patients will develop recurrent disease with many being treated with multiple therapeutic regimens. Future work will compare the clinical features of this LT survivor cohort of “exceptional” responders with the characteristics of HGSC patients with less favorable outcomes.

Sedative-like effect of intraperitoneal GABA administration in the open field test

Gamma-Amino Butyric Acid (GABA) is the main inhibitor neurotransmitter of the Central Nervous System (CNS). Its peripheral administration has been matter of discussion. On the one hand, it has been reported that it does not cross the Blood-Brain Barrier (BBB), and, on the other hand, it has been associated with multiple therapeutic regimens and supplements by peripheral administration. The aim of the present study is to elucidate the possibility of a central sedative effect when administered peripherally. An experimental cohort of 90-day-old Holtzman male rats weighing 240-270 g was used. It was divided into 2 groups: saline-controls (n = 9) and GABA treated rats (12.5 mg/kg, n = 9). Both groups were intraperitoneally injected. The motor behavioral patterns displayed in the Opto Varimex (OVM) were studied. Vertical, horizontal, ambulatory and non-ambulatory movements and the number of movements were recorded in an automated way. Horizontal movements constitute the integration of ambulatory and non-ambulatory movements. Student t test was used comparing groups. In this experiment, there were non-significant downward trends in vertical, ambulatory, non-ambulatory and number of movements. Ambulatory and non-ambulatory tendencies acquired significance when treated together as horizontal movements (p &lt; 0.05). We may conclude that peripheral administration of GABA produced a decrease of the horizontal movements in the open field test. It may be interpreted as a sedative effect, suggesting a passage of GABA through BBB, with central effects. However, there are several alternative possibilities to explain present findings. Other experiments will elucidate the implications or scope of the present findings.

Calcio y vitamina D en la paciente climatérica

Osteoporosis is characterised by reduced mineral density and bone mass, microarchitecture alterations and increased skeletal fragility. Multiple therapeutic regimens have been designed to prevent or treat bone loss in postmenopausal women and the elderly.The first step in the prevention or treatment of osteoporosis is ensuring adequate nutrition, particularly maintaining a correct intake of calcium and vitamin D.Vitamin D increases intestinal absorption of calcium and phosphate. Low concentrations of vitamin D are associated with deterioration in the absorption of calcium, a negative calcium balance, and a compensatory increase in parathyroid hormone, resulting in excessive bone resorption, and loss of bone density.

Screening for osteo-renal involvement in the Romanian HIV cohort

Background When assessing comorbidities in HIV-infected patients, the bone and the kidney represent important target organs that can potentially be affected by both virus and antivirals. Given the particular characteristics of the Romanian HIV cohort [1], most of the patients have experienced HIV infection in childhood and have received multiple therapeutic regimens since the advent of antiretroviral (ARV) therapy. Thus, the need to screen for osteo-renal impairment in these patients is high on the priority list [2].

Patient-Derived Xenografts Accurately Capture Clinical Responses to Treatment

ABSTRACT Aim: The inability to distinguish patient populations that are most likely to respond to different treatments is a continuing challenge for medical oncologists. Technologies that can be broadly applied to all patients, which enable multiple therapeutic regimens to be evaluated simultaneously to identify the ones most likely to be clinically beneficial, are needed. Drug sensitivity screening in patient-derived xenografts (PDXs) is a viable solution. In this study we examined the capacity of PDXs to replicate patient outcomes across a variety of solid tumors and treatments and report performance metrics highlighting the clinical utility of this tool. Methods: Tumor tissue from 495 cancer patients was engrafted into immunodeficient mice to generate PDX models. Of these, 65 were screened against the treatments received by the corresponding patient. Patient clinical responses and model drug responses were assessed and correlated using RECIST criteria, with parameters, including sensitivity, specificity, and predictive values, calculated to determine the capacity of PDX responses to capture patient responses. Results: Positive (complete and partial response as well as stable disease) and negative (progressive disease) patient outcomes to treatment were accurately replicated by PDXs, regardless of tumor type or treatment. Based on 96 correlations in 65 patients, we calculated a sensitivity of 99% (72/73 correlations) and specificity of 70% (16/23 correlations) for our PDX drug screens, as well as predictive values of 91% (72/79 correlations) and 94% (16/17 correlations). Despite patient exposure to first-line regimens, PDX models generated from the first resection retained the ability to reproduce outcomes to treatments used for recurrent disease. Conclusions: PDXs accurately reflect clinical responses and have strong potential to correctly guide an oncologist to treatments most likely to yield a favorable patient response, whilst avoiding those that would not. Integration of PDX technology into routine cancer care will re-shape clinical decision-making paradigms in oncology, generating better patient outcomes and eventually help cancer be managed as a chronic disease. Disclosure: M. Hidalgo: I am on the Scientific Advisory Board of Champions Oncology; A. Davies: I am an employee of Champions Oncology and I own stock in the company; D. Vasquez-Dunddel: I am an employee of Champions Oncology and I own stock in the company; D. Ciznadija: I am an employee of Champions Oncology and own shares in the company; A. Katz: I am an employee of Champions Oncology and I own stock in the company; D. Sidransky: I am on the Board of Directors for Champions Oncology and I own stock in the company; K. Paz: I am an employee of Champions Oncology and I own stock in the company. All other authors have declared no conflicts of interest.