Mild Vomiting Research Articles

Socio Demographic Characteristics Of Pregnant Women Who Are Experiencing Nausea Vomiting In Rural Areas Of Banyumas Regency

Nausea vomiting in pregnancy or commonly referred to as morning sickness is a common complaint in the first trimester, although it can also occur in the second trimester or all trimester. The purpose of this study was to determine the characteristic of pregnant women who experience morning sickness in rural areas. Respondents in this study were pregnant women who experienced morning sickness during July-September 2018 in rural areas of Banyumas District, Central Java Province, Indonesia. This study have used quantitative descriptive design.The results of univariate analysis of 61 pregnant women involved, 77% age of mothers were at low risk, 39,3% were junior high school education, 82% were not working, 60% were pregnant in the first trimester, 61,7% were multigravida, 55.7% did not have a history of nausea and vomiting, and 73,8% in the category of mild nausea and vomiting. It can be concluded that pregnant women who experience nausea and vomiting in rural areas are the majority of those who are of low risk, do not work, are pregnant for the first time, have early pregnancy, and with mild nausea and vomiting.

May solid food refusal and other non-specific neurological symptoms be an early symptoms of Vitamin B12 deficiency in complementary feeding period?

Aim: In this study, we showed an early symptoms of VB12 deficiency in infancy complementary feeding period (CFP) without hematologic findings. Vitamin B-12 (VB12) deficiency can result in severe neurological degeneration within the first year of life. In literature, symptoms of VB12 deficiency in infant were described with hematologic findings which were like a pernicious anemia. Material and Methods: A 104 of 1,848 mother-infant pairs admitted for well-child visits between January 2018 and December 2018 were included in the study. All babies were diagnosed with vitamin B12 deficiency. All baby-mother pairs were monitored during the CFP were included in the study. Overall, 83 mother who met the inclusion criteria and who agreed to participate in the study and their babies, were included in the study.Results: The cause of follow-up of these children was refusal to breastfeed and irritability in 21 infants (25.3%). There were 19 infants (22.9%) with solid food refusal, 16 infants (19.2%) with sleeping problems, and 16 infants (19.2%) with failure to thrive. In the remaining 11 infants (13.2%), there were mild hypotonia, microcephalia, vomiting, and growth retardation. The mean age for the development of these symptoms was 5.5 ± 1.7 months, while the mean age of being diagnosed with VB12 deficiency was 6.4±1.2 months. Conclusions: In this study, symptoms of VB12 deficiency without any hematological symptoms and not caused by other organic causes, and arising during the period of transition to complementary feeding, were demonstrated. Physician must be aware of early findings of VB12 deficiency before severe neurological findings and hematological sypmtoms.

Low-dose apatinib monotherapy in advanced chemotherapy-refractory small cell lung cancer: a case series and literature review.

The therapeutic regimen for small cell lung cancer (SCLC) has changed little in the past several decades. Apatinib is a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib has demonstrated efficacy against advanced gastric cancer and breast cancer, and recent studies have also reported its successful use in non-SCLC; however, its efficacy in SCLC remains unclear. In this study, we used apatinib as salvage therapy for chemotherapy-refractory SCLC. Five male patients with advanced SCLC were administered oral apatinib (250 mg/day) as 2nd- to 4th-line treatment. One patient showed a partial response to apatinib, one showed stable disease, and three patients showed progressive disease. The progression-free survival durations in the patients with stable disease and partial response were 1.5 and 3 months, respectively. Only three patients showed adverse effects, including mild hypertension, vomiting, and hand–foot syndrome, respectively, all of which were manageable. Apatinib might thus be a salvage option in patients with advanced SCLC after chemotherapy.

Eltrombopag for the treatment of primary immune thrombocytopenia in 23 pediatric patients

目的评估艾曲泊帕治疗儿童原发免疫性血小板减少症（ITP）的疗效和不良反应。方法回顾性分析2015年5月至2019年3月接受艾曲泊帕治疗的23例儿童ITP患者临床资料。结果23例患者中，男11例，女12例，中位年龄11（2~17）岁。新诊断ITP 4例（17.39%），持续性ITP 8例（34.78%），慢性ITP 11例（47.83%）。艾曲泊帕中位起始剂量为25.0（12.5~50.0）mg/d。基线中位血小板计数为14（2~82）×109/L，治疗后第2周（23例）、第4周（23例）、第3个月（16例）、第6个月（11例）的中位血小板计数分别为40（4~170）×109/L、20（4~130）×109/L、60（4~110）×109/L、70（18~160）×109/L，均高于基线水平（z=-3.440，P=0.001；z=-1.964，P=0.049；z=-4.339，P<0.001；z=-5.794，P<0.001）。7例（30.43%）患者的起效时间≤7 d，10例（43.48%）患者的起效时间≤2周，总有效率为60.87%（14/23）。<6岁（6例）、6~12岁（10例）、13~17岁（7例）组的总有效率分别为33.33%（2/6）、60.00%（6/10）、85.71%（6/7），组间比较差异均无统计学意义（P>0.05）。23例患者基线WHO出血评分0、1、2级分别有4、12、7例，治疗后分别为13、7、3例，出血症状得到明显改善（χ2=7.558，P=0.006）。治疗过程中发生转氨酶、胆红素增高各4例，轻度恶心、呕吐及头晕各1例，对治疗均未造成影响。结论艾曲泊帕作为二线用药治疗儿童ITP疗效及耐受性均较好。

3-Methylcrotonyl-CoA carboxylase deficiency newborn screening in a population of 536,008: is routine screening necessary?

Objective To evaluate whether 3-methylcrotonyl-CoA carboxylase deficiency (3-MCCD) should be routinely screened in newborns. Methods Dried blood spots (DBS) were collected and analyzed by tandem mass spectrometry (TMS). Blood samples were collected from infants with positive 3-MCCD results. Targeted sequencing was performed using the extended panel for inherited metabolic diseases to detect 306 genes. The sequencing libraries were quantified and used for massively parallel sequencing on the Illumina HiSeq 2500 platform. Results A total of 536,008 infants underwent newborn screening (NBS) and 14 cases of 3-MCCD were diagnosed. The incidence of 3-MCCD in Jiangsu province was 1:38,286. During the last 3 years of follow-up, none of the subjects with 3-MCCD exhibited obvious clinical symptoms. Only two children had mild feeding difficulties and vomiting. Eleven patients had complex variants of the MCCC1 gene, and three patients had mutations in MCCC2. In total, 17 types of MCCC1 or MCCC2 variants were found, and c.639 + 2t > a was the most common mutation. Conclusions As far as the current results are concerned, 3-MCCD may be benign in Jiangsu province. However, additional investigations and a longer follow-up period are necessary to decide whether NBS of 3-MCCD is necessary or not.

Epidemiological Distribution of Reported West Nile cases in Houston, Texas, 2014-2017

ObjectiveTo demonstrate an overview of the epidemiological and clinical distribution of reportable West Nile cases in Houston, Texas, from 2015-2017.IntroductionWest Nile virus (WNV) is considered the leading cause of domestically acquired arboviral disease and is spread through mosquitoes. In general, the majority of the cases are asymptomatic. One in five people infected will display mild symptoms like fever, headache, body ache, nausea, and vomiting. Only about 1 in 150 people infected will develop serious neurologic complications such as encephalitis and meningitis. According to CDC, in 2017, there were 133 confirmed cases including 5 deaths and 14 presumptive blood donors reported in the State of Texas. Out of the confirmed cases, there were 85 neuroinvasive and 48 non-neuroinvasive disease cases.MethodsData were extracted from Houston’s Electronic Disease Surveillance System (HEDSS) from January 1, 2014, to December 31, 2017. A total of 45 confirmed cases are included in this analysis to examine the epidemiologic characteristics of the WNV cases.A confirmed case is an illness with onset of acute focal limb weakness and an MRI showing a spinal cord lesion largely restricted to gray matter and spanning one or more spinal segments.ResultsAmong the confirmed cases, 67% of were males. Age group 60 and above (47%) had the highest proportion of WNV cases. Whites (26%) represented the highest number of confirmed cases followed by Hispanics (24%).Seventy six percent of the cases were hospitalized. Non-neuroinvasive clinical presentations found among confirmed WNV cases were fever (94%), headache (76%) followed by chills and rigors (68%). Among the neuroinvasive presentations, altered mental status had the highest proportion (24%), followed by stiff necks (18%), Ataxia (12%), and seizure (9%).ConclusionsWNV is mostly prevalent in White male adults over 60 years of age, with majority of cases have common neuroinvasive symptoms like altered mental status, stiff necks, and Ataxia. For non-neuroinvasive cases clinical symptoms were fever, headache, chills and rigors.WNV infection is a markedly underreported disease as most of the infected people do not seek medical care due to mild or no symptoms. Currently there are no specific treatments available. Thus, continued monitoring and surveillance activities are warranted for prevention and control of WNV complications as well as decreasing the risk of infection.ReferencesCDC: West Nile Virus [Internet]. Atlanta: Center for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), and Division of Vector-Borne Diseases (DVBD); Last reviewed: September 19, 2018.Available from: https://www.cdc.gov/westnile/index.html

Acute Tubular Necrosis associated with the Ketogenic Diet in a Child with Intractable Epilepsy

The ketogenic diet (KD) has been used as an effective antiepileptic therapy for intractable childhood epilepsy. However, various adverse effects have been reported with use of the KD. We report a case of a child who developed acute tubular necrosis subsequent to therapy with KD. A 5-year-old girl had myoclonic epilepsy with developmental delay. She was under the treatment with antiepileptic drugs since the age of 3 months and on the KD during the past 18 months. Proteinuria persisted intermittently with the initiation of the KD and subsequently increased in the past 2 months. She was admitted with intermittent mild fever, vomiting, and lethargy for the past 3–4 weeks. At the time of admission, she presented with hypertriglyceridemia, heavy proteinuria, renal Fanconi syndrome, and acute kidney injury. Renal sonography showed a marked increase in the size and parenchymal echogenicity of both kidneys. A renal biopsy revealed acute tubular necrosis accompanied by early interstitial fibrosis. After the withdrawal of the KD and supportive therapy, without changing other anticonvulsants and their dosages, improvement of renal function was observed. Proteinuria had disappeared after 1 month and kidney size returned to normal after 8 months. It is hypothesized that the KD can induce and/or aggravate the renal tubulointerstitial injury in some patients who are under the treatment with anticonvulsants. Key words: Acute kidney injury; Epilepsy; Ketogenic diet; Proteinuria

Transient visual loss with methotrexate, leucovorin chemotherapy for gestational trophoblastic neoplasia: Happenstance or beyond?

Methotrexate chemotherapy (CT) is a standard for low-risk gestational trophoblastic neoplasia. Its use is associated with minimal toxicities and is chiefly composed of mild nausea and vomiting. Acutely occurring and self-limiting loss of vision has not been reported in the literature as a potential side effect. We discuss such a case with a transient and self-limiting visual loss in a patient on two consecutive courses of the planned CT. We advocate a further in-depth research to find the cause of such an association.

Efficacy and safety of chloral hydrate combined with dexmedetomidine for sedation during echocardiography in pediatric patients with Williams-Beuren syndrome

Objective To evaluate the efficacy and safety of chloral hydrate combined with dexmedetomidine for sedation during echocardiography in pediatric patients with Williams-Beuren syndrome. Methods Eighteen pediatric patients diagnosed with Williams-Beuren syndrome by genetic testing, aged 5-58 months, scheduled for elective echocardiography under sedation, received oral chloral hydrate 50 mg/kg.Vital signs were measured every 5 min, and sedation was assessed using Ramsay sedation score.When Ramsay sedation score<4 points 20 min later, intranasal dexmedetomidine 1 μg/kg was given as rescue sedative.Medicine used, vital signs, onset time, moderate and deep sedation duration and emergence time were recorded. Results The success rate of sedation with chloral hydrate alone was 38.9% and with chloral hydrate and dexmedetomidine 61.1%.The onset time, sedation duration and emergence time were(15.7±1.9) min, (75±26) min and(52±25) min, respectively, in pediatric patients received chloral hydrate alone.The onset time, sedation duration and emergence time were(33.2±3.4) min, (83±49) min and(61±46) min, respectively, in pediatric patients received chloral hydrate and dexmedetomidine.The onset time was significantly prolonged in pediatric patients received chloral hydrate and dexmedetomidine than in pediatric patients received chloral hydrate alone(P<0.05). Heart rate, respiratory rate and SpO2 were stable during sedation in all pediatric patients, and nausea and mild vomiting were found in 3 pediatric patients received chloral hydrate and in 6 pediatric patients received chloral hydrate and dexmedetomidine, and no other adverse reactions were observed. Conclusion Oral chloral hydrate 50 mg/kg combined with intranasal dexmedetomidine 1 μg/kg provides reliable sedative efficacy and exerts less influence on respiratory and circulatory function with higher safety when used for echocardiography in pediatric patients with Williams-Beuren syndrome. Key words: Dexmedetomidine; Chloral hydrate; Heart diseases; Echocardiography, doppler, color; Conscious sedation

All That Bleeds! Visceral Artery Pseudo Aneurysm as a Rare Cause of Recurrent Fresh Gastrointestinal Bleeding

Visceral artery aneurysm and pseudoaneurysm are rare with incidence of 0.1-2%.We report a case of pancreato-duodenal artery pseudoaneurysm presenting as recurrent upper and lower GIB. CASE PRESENTATION: A 57 year old male with past history of COPD, hypertension, GERD, chronic hepatitis C,and alcohol abuse, presented with diffuse abdominal pain.His symptoms started nearly two weeks prior with hematemesis and lower GIB. An upper endoscopy and colonoscopy failed to identify source of bleeding.Two days later he had another episode of fresh upper and lower GI bleeding. Repeat endoscopy revealed no source.On third occassion patient reported diffuse abdominal pain, followed by mild nausea,vomiting and large amount of fresh blood hematemesis and bleeding per rectum. Abdominal CT angiogram revealed acute on chronic pancreatitis, atrophy of pancreatic body and multiple pseudocysts.A 4.6x3.2 cm pseudoaneurysm anterior to splenic artery anatomically was located in close proximity to posterior gastric wall with possible erosion. During endovascular repair a small branch of gastro-duodenal artery was identified as vessel of origin. Multiple micro-catheter coils were used to fill and obliterate the sac and feeding vessel. At six month follow up pseudoaneursym was stable on imaging. DISCUSSION ETIOLOGY: True aneurysms are caused by hypertension, atherosclerosis,and connective tissue disease.Two-thirds of VAPA are secondary to pancreatitis and leaking of proteolytic enzymes.PRESENTATION:Most cases present with vague abdominal symptoms.If ruptured, patients present with anemia and hemodynamic instability.DIAGNOSIS:Color Doppler can display inflow and outflow of blood in sac, known as “yin-yang sign”.Transcatheter angiography remains gold-standard for diagnosis as it can provide definitive diagnosis, has highest sensitivity (100%) and therapeutic potential.TREATMENT: Treatment is indicated if a visceral aneurysm size is >2cm. Women of child bearing age or pregnant should also undergo treatment.A pseudoaneurysm must be treated immediately as rate of expansion is much rapid(76.3% vs 3.1%). Treatment options include endovascular(stent,embolization),percutaneous thrombin injection,and surgery(vessel ligation,arterial bypass,sac exclusion). CONCLUSION:This case reports highlights importance of including VAA and VAPA in differential diagnosis of GI bleeding and use of alternative diagnostic modalities when endoscopy and colonoscopy fail to reveal a source of bleeding.1954_A Figure 1. Non contrast CT Abdomen showing extensive pancreatic destruction1954_B Figure 2. Contrast enhanced CT showing a large pseudoaneurysm in proximity of posterior gastric wall1954_C Figure 3. Intra operative angiogram before and after the endovascular repair.

Safety and immunogenicity of the Cuban heptavalent pneumococcal conjugate vaccine in healthy infants. Results from a double-blind randomized control trial Phase I

BackgroundCuba has a new pneumococcal conjugate vaccine candidate (PCV7-TT). This study evaluates the safety and immunogenicity in healthy infants using 2p+1 vaccination schedule. MethodsA phase I, controlled, randomized and double blind clinical trial was designed. 30 unvaccinated healthy infants were included. 20 subjects were assigned to study group (PCV7-TT) and 10 to control group (Synflorix®) to receive the vaccines at 7, 8 months of age (primary series) and 11 months (booster dose). Blood samples were collected 30 days after second dose and post booster for antibodies measure analysis by ELISA and OPA. The statistics analysis included the frequency of occurrence for adverse events and the immune response. Non-parametric tests were used to compare the immune response. The clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173 available at http://registroclinico.sld.cu. ResultsOverall, the safety profile of PCV7-TT was similar to Synflorix®. Local reactions were predominant and systemic events were mild in severity. Swelling and redness were frequently associated with PCV7-TT mainly after the first dose (50% and 40% respectively). 15% and 10% of subject reported severe swelling after first dose with PCV7-TT and after second dose with Synflorix®. Mild fever (≥38–≤39), vomiting and sleep disturb were the systemic events reported. 100% of infants achieved pneumococcal IgG antibody concentrations ≥0.35 µg/ml after booster dose for serotypes 1, 14, 18C and 19F in each vaccine group. For serotypes 5, 6B and 23F, more than 80% infants vaccinated with Synflorix® or PCV7-TT achieved protective IgG GMC ≥ 0.35 µg/ml after booster dose. OPA proportion’s responders to the seven common serotypes were 89.5% or more after the primary dose and 100% after booster dose in vaccinated with PCV7-TT. ConclusionsThe Cuban PCV7-TT is safe, well tolerated and immunogenic in healthy infants.

Efficacy observation of GDP regimen for treatment of relapsed and refractory non-Hodgkin lymphoma

Objective To analyze the efficacy of GDP regimen for treatment of relapsed and refractory non-Hodgkin lymphoma (NHL). Methods The clinical data of 40 patients with relapsed and refractory NHL in the Third Hospital of Peking University from January 2009 to June 2014 were retrospectively analyzed. All the patients underwent GDP regimen (gemcitabine, dexamethasone, cisplatin). The clinical features, laboratory data and survival status were analyzed. Results The overall response rate (ORR) of 40 patients was 67.5% (27/40) with 27.5% (11/40) complete remission (CR) rate and 40.0% (16/40) partial remission rate. The 3-year overall survival (OS) rate was 86.5% and the OS rate of 5-year was 28.8%. The ORR and 3-year OS rate in B-cell lymphoma and T-cell lymphoma were 69.6% (16/23) vs. 52.9% (9/17) (P= 0.283), 90.9% vs. 80.7% (P= 0.480). The CR rate in patients with gastrointestinal tract involvement was better than that in patients without gastrointestinal tract involvement (P= 0.049). Meanwhile, the patients with gastrointestinal tract involvement were superior in 3-year OS rate (89.3% vs. 76.2%, but the difference was not statistically significant (P= 0.237). The major side effect was hematological adverse reactions. The incidence of grade Ⅲ/Ⅳ neutropenia was 47.5%, the rate of Ⅲ/Ⅳ thrombocytopenia was 40.0% and the rate of Ⅲ/Ⅳ anemia was 17.5%. Non-hematological adverse reactions included mild nausea and vomiting. Conclusions GDP regimen is effective and well tolerated in relapsed and refractory NHL with better efficacy for gastrointestinal tract involvement NHL patients. Key words: Lymphoma, non-Hodgkin; Recurrence; Refractory; Antineoplastic combined chemotherapy protocols; Efficacy; Adverse reactions

Influence of Pharmacist Recommendations for Chemotherapy-Related Problems in Diabetic Cancer Patients

Drug related-problems pose additional worse outcomes in cancer patients treated with chemotherapy. A vital role of the clinical pharmacist is the detection and prevention of drugrelated problems. The provision of patient education is an important step to reduce and prevent drug-related problems during chemotherapy administration. The objective of this study was to assess the occurrence of drug-related problems and the importance of effective provision of patient education and appropriate recommendations by the clinical pharmacist in reducing and solving of these problems in diabetic patients suffering from cancer. A prospective study carried out on 50 diabetic patients as a single group with new diagnosis of diverse cancer types eligible for chemotherapy adminitration recruited between September 2014 and April 2015 at the oncology unit in one of the Teaching and Research Hospital (Istanbul-Turkey). Drug-related problems were evaluated, and proper patient education alongside pharmacist recommendation regarding chemotherapy was provided during the required chemotherapy protocol schedule. (n=65) of the drug-related problems were contributed to inappropriate IV fluid selection; (n=33) were attributed to low drug dose prescribed, and (n=30) to high drug dose prescribed. Drug-related problems totally solved due to clinical pharmacist recommendations were 69.57% (n=80). There was a significant increase in the occurrence of paleness (P=0.0001); urinary frequency (P=0.003); loss of appetite (P=0.0001), nausea (P=0.0001), vomiting (P=0.0001); and numbness (P=0.0001). A significant decrease in the occurrence and severity of chemotherapy-related adverse effects was observed as a mild urinary frequency (P=0.0001) and mild vomiting (P=0.0001) after the clinical pharmacist recommendations and provision of patient education. Results of this study revealed that diabetic cancer patients are definitly prone to the occurrence of drug-related problems and adverse drug reactions. Clinical pharmacist is expected to provide a well-defined education and care to those patients and the outcomes of pharmacist recommendations may diminish and prevent many drug-related problems and adverse drug reactions and by this, influence patients’ desire to complete the course of chemotherapy.

The Effects of Mini-dose Aspirin on Hepatic Functions

Aspirin is the prototype of NSAIDs, that’s widely used as an anti aggregant for prophylaxis of ischemic heart disease (IHD), usually is given as 75 mg/d, aspirin is a non selective COX inhibitor, as well as is the only irreversible inhibitor of COX enzymes. Aspirin is metabolized into acetic acid and salicylates, hence aspirin can cause salicylism, in which signs and symptoms may range from mild nausea and vomiting, abdominal pain, lethargy, tinnitus, and dizziness to severe such as seizure or cerebral edema depending on the dose consumed. Although very-low-dose (mini-dose) aspirin is used increasingly as a platelet aggregation inhibitor, no studies have been published on whether aspirin's hepatic effects occur at dosages of <0.5 gm/day. The aim of the present study was to evaluate the effects of commonly used mini-dosages of aspirin on hepatic functions in elderly patients for prophylaxis of IHD. About 54 elderly patients are investigated, they were given 75mg, 150 and 325 mg, for about 5 months, CBC and hepatic tests were taken before and after treatment. The serum of blood glucose is also wvaluated. The main result is that hepatic functions in patients receiving 75, or 150 mg /d still around normal ranges, but significant hepatic alterations have occurred in patients treated by 325 mg/d., as well as the incidence of hypoglycemia.

Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma

BackgroundCholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far.Case presentationIn this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively. The patient finally achieved an 8.5-month partial response (PR) from the CART-EGFR therapy and a 4.5-month-lasting PR from the CART133 treatment. The CART-EGFR cells induced acute infusion-related toxicities such as mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever, accompanied by escalation of IL-6 and C reactive protein (CRP), acute increase of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase, and grade 2 lichen striatus-like skin pathological changes. The CART133 cells induced an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release, which needed emergent medical intervention including intravenous methylprednisolone.ConclusionsThis case suggests that CART cocktail immunotherapy may be feasible for the treatment of CCA as well as other solid malignancies; however, the toxicities, especially the epidermal/endothelial damages, require a further investigation.Trial registrationClinicalTrials.gov NCT01869166 and NCT02541370.

Hemostatic disorders induced by skin contact with Lonomia obliqua (Lepidoptera, Saturniidae) caterpillars

ABSTRACTPatients envenomed by Lonomia sp caterpillars initially experience a mild burning pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients can rapidly progress to a severe coagulopathy that presents as visceral or intracerebral hemorrhaging. We studied the hemostatic alterations that occurred in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and presented at the Hospital São Vicente de Paulo (Passo Fundo, RS), Brazil during the summers of 1993 and 1994 when Lonomia antivenom was not yet available for treatment. The patients were classified into to 4 clinical groups: 0 (two patients), I (eight patients), II (two patients), and III (two patients). The patients were admitted to the hospital between 4 hours and five days after contact with the caterpillars. In this study, the coagulation parameters of the patients were followed up for up to 172 hours after the accidents. The patients received no treatment with the exceptions of two patients who received blood transfusions and antifibrinolytic treatment. The observed abnormalities related to blood coagulation and fibrinolytic factors were similar regardless of the severity of the bleeding symptoms. These findings suggest that alterations in hemostatic parameters without thrombocytopenia are not predictors of the seriousness of such accidents. Thus, consumptive disorder and reactive fibrinolysis are not proportional to mild coagulopathy. Furthermore, these patients recovered. The hemostatic parameters of most of the patients normalized between 96 and 120 h after the accident.

A Dose Escalation Study of RP6530, a Novel Dual PI3K δ/γ Inhibitor, in Patients with Relapsed/Refractory T-Cell Lymphoma

Introduction: The δ isoform of PI3K is highly expressed in cells of hematopoietic origin. The γ isoform is associated with T-lymphocytes and neutrophils and plays a distinct role in T-cell function. Since δ/γ isoforms are synergistic in the growth and survival of certain T-cell malignancies, dual targeting of PI3K δ/γ is an attractive intervention strategy in patients with T-cell lymphoma. RP6530 is a novel, highly specific dual PI3K δ/γ inhibitor with nanomolar inhibitory potency for both isotypes. It has shown acceptable safety profile and efficacy in patients (pts) with advanced hematologic malignancies in a Phase 1 study (ASH 2015). Herein, we present the preliminary results from an ongoing Phase 1/1b, dose escalation study of RP6530 in 11 pts with mature T-cell neoplasms (NCT02567656).Methods: The study consists of dose escalation cohorts to determine the MTD of RP6530 using a standard 3+3 design, followed by two expansion cohorts enrolling 20 pts with peripheral T-cell lymphoma (PTCL) and 20 pts with cutaneous T-cell lymphoma (CTCL). Pts with a diagnosis of PTCL or CTCL who have received at least one prior systemic therapy, ECOG performance status ≤ 2 and measurable/evaluable disease are eligible. This study evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and clinical activity of RP6530 administered twice daily (BID) in 28-day cycles. Responses were evaluated for PTCL and CTCL based on IWG criteria (Cheson 2014) and the modified Severity Weighted Assessment Tool (mSWAT) respectively. Dose limiting toxicity (DLT) was defined by a toxicity of grade 3/4 that is considered related to treatment during the first cycle of treatment.Results: To date eleven pts (6 PTCL and 5 CTCL) (5 males and six females) have been enrolled at three dose levels: 200 mg BID, 400 mg BID and 800 mg BID. ECOG performance status score was 0/1/2 in 10/1/0 pts, respectively, with a mean age of 68 yrs (range 52-76). Pts had a median of 3 (range: 3-6) prior treatment regimens, and 5 pts had refractory disease and 6 relapsed on prior treatments.RP6530 was well tolerated without any DLT or related serious adverse event reported to date. A total of 52 non-serious adverse events were reported: 41 Grade 1/2 and 11 Grade 3/4. The most common adverse events included mild vomiting (18%), diarrhoea (18%), fatigue (18%), and rash (18%). No Grade 3/4 adverse events were deemed related to RP6530 except for ALT/AST elevation in one pt. No pt discontinued treatment due to a safety issue. Dose-proportional increases in plasma concentrations were observed in PKs. Dose escalation is currently ongoing at 800 mg BID.Five pts were evaluated for responses at Cycle 3, Day1. Two pts (1 PTCL and 1 CTCL) experienced PR (40%) that are ongoing >5 months, and three pts experienced stable disease lasting for >3 months (60%). Three pts experienced rapid disease progression during first cycle, and discontinued treatment prematurely.Conclusion: This ongoing study of RP6530 demonstrated an acceptable safety profile at doses evaluated, with a promising clinical activity. The results support further evaluation of RP6530 in pts with mature T-cell neoplasms. DisclosuresOki:Novartis: Research Funding. Barde:Rhizen Pharmaceuticals SA: Employment. Penmetsa:Rhizen Pharmaceuticals SA: Employment. Viswanadha:Incozen Therapeutics: Employment.

Clinical Observation of Bevacizumab Combined with S-1 in the Treatment of Pretreated Advanced Esophageal Carcinoma.

Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m2·d on day 1-14, 21 days as a cycle of treatment and repeated until either pro- gressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response (CR+PR) rate was 22.4% (17/76) and disease control (CR+PR+SD) rate was 61.8% (47/76) respectively. The median follow-up time was 20 months (range from 9 to 44 months). The median progression-free survival (PFS) was 4.9 months (95% CI 4.4-5.5) and the median overall survival (OS) was 8.1 months (95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months (95% CI 3.3 to 6.3) and 8.5 months (95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence (median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis (median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia (84.2%), grade I-II hand and foot syndrome (51.3%), grade I-II nausea (48.7%), mild epistaxis (30.1%) and mild vomiting (14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient (1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.

Effect of Hydrotubation in Unexplained Infertility – A Randomized Controlled Trial

&lt;p&gt;Unexplained infertility is a major gynecological problem with complex etiolgy. Partial tubal blockage with inflammatory reaction and thick mucus plugs in fallopian tubes and cervix is one of the likely causes in such cases. This study is based on the hypothesis that women having unexplained infertility could be helped by transcervical flushing of fluid through the fallopian tubes which would remove reversible blocking factors and help in achieving pregnancy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective:&lt;/strong&gt;&lt;strong&gt;Â Â &lt;/strong&gt;To compare the outcome of hydrotubation&lt;br /&gt; in unexplained infertility in clomiphene citrate stimulated cycles with control group (no Hydrotubation).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting:&lt;/strong&gt;&lt;strong&gt;Â Â &lt;/strong&gt;Infertility Centre of a Public Sector Hospital.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study Design:&lt;/strong&gt;&lt;strong&gt;Â Â &lt;/strong&gt;A two years Prospective randomized controlled trial from Jan 2014 to Dec 2015.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method:&lt;/strong&gt;&lt;strong&gt;Â Â &lt;/strong&gt;128 women participated in the study. Participants were divided into study and control group with 64 members in each group. Ovulation induction was done with clomiphene citrate in all the participants and confirmed by ovulation detection strips and follicular tracking on Ultrasonography. 50 cc cocktail of inject-ion (inj.) kanamycin 1 gm, inj. hydrocortisone and normal saline was injected transcervically in study group for three consecutive days from the next day after end of menstruation. No hydrotubation was done in control group. Main outcome measures were number of conceptions within next 3 cycles and complications of hydrotubation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt;&lt;strong&gt;Â Â &lt;/strong&gt;In hydrotubation group, 20 women conceived. Out of these, 14 women conceived in the same cycle in which hydrotubation was done while 6 pregnancies occurred in subsequent cycle. 4 pregnancies occurred in the control group. Complications of hydrotubation were mild abdominal pain (59 women), vomiting (49 women) and Per vaginum bleeding (18 women). There were significantly more pregnancies in women who experienced right shoulder tip pain after the procedure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt;&lt;strong&gt;Â Â &lt;/strong&gt;In women with unexplained infertility, tubal hydration can increase conception rate and decrease the time to achieve pregnancy.&lt;/p&gt;&lt;p&gt;Â &lt;/p&gt;

Olaparib for the treatment of BRCA-mutated advanced ovarian cancer.

The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of olaparib, a first-in-class treatment for advanced treatment-refractory ovarian cancer, are reviewed. Olaparib (Lynparza, AstraZeneca) is an oral inhibitor of poly(ADP-ribose) polymerase (PARP) proteins that play a key role in DNA repair and genomic stability. Olaparib is indicated for use in treating certain patients with advanced, recurrent ovarian cancer who have mutations of the breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2). In patients with BRCA-mutated cancers, olaparib blocks vital PARP-mediated tumor cell DNA repair mechanisms, leading to "synthetic lethality" and selective tumor cell death. In Phase II clinical trials including patients with platinum-sensitive, platinum-resistant, and platinum-refractory ovarian cancers, olaparib significantly improved progression-free survival, with similar rates of response reported in patients with BRCA1- and BRCA2-mutated disease. Olaparib is generally well tolerated; the most commonly reported adverse events in clinical trials were mild nausea, fatigue, vomiting, and diarrhea. Severe anemia and severe fatigue can occur in association with olaparib treatment. Concurrent administration of olaparib and strong or moderate inducers or inhibitors of cytochrome P-450 isozyme 3A should be avoided, as use of those agents may alter plasma concentrations of olaparib. Olaparib is a novel PARP inhibitor that is efficacious and well tolerated in patients with BRCA-mutated advanced ovarian cancers who have received three or more lines of prior treatment.