The FDA review leading to accelerated approval of carfilzomib is described. A single arm trial enrolled 266 patients with multiple myeloma refractory to the most recent therapy, and who had received prior treatment with bortezomib and an immunomodulatory agent (IMID). Patients received carfilzomib by intravenous (IV) infusion over 2 to 10 minutes at a dose of 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 of the 28 days of cycle 1, and at a dose of 27 mg/m2 on the same schedule in cycle 2 and subsequent cycles. The primary efficacy endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) using International Myeloma Working Group response criteria. The safety of carfilzomib was evaluated in 526 patients with multiple myeloma treated with various dosing regimens. The ORR was 23%. The median duration of response was 7.8 months. Most common adverse reactions associated with carfilzomib infusion were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and fever. Most common serious adverse events were pneumonia, acute renal failure, fever, and congestive heart failure. Infusion reactions to carfilzomib could be reduced by pre-treatment with dexamethasone and IV fluids. On July 20, 2012, FDA granted accelerated approval of carfilzomib for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an IMID and who have demonstrated disease progression while on therapy or within 60 days of completion of the last therapy.

Background:

Acute diarrhea remains a major public health issue worldwide, with gastroenteritis agents associated with a high morbidity, especially in infants and young children. A 1-year study (2009-2010) of rotavirus (RV)-caused pediatric diarrhea was performed on hospitalized children admitted with symptoms of acute diarrhea to the University Hospital of Patras, Greece.

Methods:

Twenty-nine fecal samples were investigated for RVs, adenoviruses (AdVs), and enteroviruses (EVs) in an attempt to characterize these enteric viruses, which have been implicated in hospitalized diarrhea.

Results:

A 44.8% (13/29) incidence of viral infection was reported for the viral targets. Monoinfections accounted for 31% (9/29), while bi-infections accounted for 13.4% (4/29). Sequencing of positive samples allowed identification of RVs G4P[8] (2/29), G9P[8] (1/29), and interestingly of the rare type G12P[8] (2/29). AdV types 1, 2, and 6 were also identified in 4/29, 1/29, and 1/29 of the samples, respectively. Regarding the EVs, EV71 (2/29), coxsackievirus A4 (1/29), echovirus 11 (1/29), and EV96 (1/29) were typed.

Conclusion:

The results of the present study, and specifically the detection of rare RV G12 and EV71 strains, address the need for continuous epidemiological surveys to provide epidemiological pictures of pediatric viral infections circulating in the community.

BACKGROUND:

Ulcerative colitis (UC) is associated with enhanced production of reactive oxygen species and altered angiogenesis. Molecular hydrogen has been documented as a novel antioxidant to treat various reactive oxygen species-related diseases. The present study aimed to investigate the effects of hydrogen on UC using a rat model.

MATERIALS AND METHODS:

UC in rats was induced with intracolonically administrated acetic acid. Hydrogen was supplied through intraperitoneal injection of 10 or 20 mL/kg hydrogen-rich saline. The hydrogen treatment was performed once every 2 d and lasted 2 wk. The stool consistency and weight loss were used to evaluate UC development. Colonic mucosal damage at the end of the experiment was scored using the macroscopic and microscopic observations. Vascular endothelial growth factor expression in the colonic mucosa was determined using immunohistochemistry.

RESULTS:

The administration of acetic acid induced acute rat UC, as indicated by diarrhea, weight loss, and colonic mucosal damage. Treatment with hydrogen-rich saline reduced the weight loss and diarrhea and alleviated the colonic mucosal damage in the UC rats. In addition, the expression of vascular endothelial growth factor in the UC rats increased and could be inhibited by hydrogen treatment.

CONCLUSIONS:

Antioxidative hydrogen-rich saline effectively protected the rats from UC, which might be, at least in part, because of inhibition of vascular endothelial growth factor.

During an acute outbreak of Norovirus in the local area, a 77-year-old woman was admitted with a short history of diarrhoea and vomiting. A working diagnosis of viral gastroenteritis complicated by acute renal failure, secondary to dehydration, was made. Despite judicious fluid resuscitation and regular antiemetics, the patient's symptoms persisted with only mild improvement in her renal function. An abdominal radiograph revealed evidence of significant small bowel obstruction and subsequent CT of the abdomen and pelvis identified a 1.5 cm intraluminal density at a transition point raising the suspicion of gallstone ileus. An urgent laparotomy with stone removal was carried out without complications. The patient recovered well postoperatively and was discharged home after 3 days.

Chronic diarrhea is defined as the passage of loose stools that last for more than 4 weeks. Although generally it is estimated that the prevalence of chronic diarrhea only ranges 3-5% of population, but it poses some specific equally essential challenges compared to acute diarrhea because there are many differential diagnosis that should be considered as the cause of chronic diarrhea. One of them includes colorectal cancer and the small intestinal bacterial overgrowth, known as SIBO. In general, chronic diarrhea can be categorized into watery, malabsorption, and inflammatory diarrhea. A proper history taking, physical examination and laboratory investigation is therefore necessary for clinician in managing chronic diarrhea. Overall, the management of chronic diarrhea includes two types, i.e. supportive and pharmacological management both for infectious and non-infectious etiologies. Pharmacological treatment can also be classified into two kinds of treatment including symptomatic and causal treatment, which can be achieved through empirical therapy.

The best age for the arterial switch operation (ASO) in complete transposition of great arteries with ventricular septal defect is usually considered to be within six months. This is because of severe pulmonary arterial hypertension and pulmonary arterial obstructive pathological changes. There are few reports on ASO surgery in children older than three years old.We studied 41 children, including 24 males and 17 females, from January 2010 to December 2011. They were divided into three groups by operation age; 15 patients were < 1 year old, 13 were 1 - 3 years old, and 13 were > 3 years old. Associated cardiac abnormalities included patent ductus arteriosus in six cases, atrial septal defect in five cases, and mitral regurgitation in two cases. All the patients had echocardiography before the operation. Seventeen patients underwent a coronary computed tomography examination and five patients underwent right heart catheterization. All ASO surgeries were performed under inhalation anesthesia and hypothermic cardiopulmonary bypass.Three operative deaths occurred. Two were in the < 1 year old group, who died from severe postoperative low cardiac output. The other was two years old and died of postoperative multiple organ failure. There was no significant difference in postoperative mortality and the recent mid-term survival rate among the three groups. Thirty-eight cases were followed up for an average of 11.2 months, ranging 6 - 20 months. One seven years old patient died of acute diarrhea and electrolyte disturbance arrhythmia caused by food poisoning. Three patients more than three years old still had residual pulmonary arterial hypertension.Children older than three years old can still undergo the ASO procedure, but residual pulmonary hypertension is present.

Abstract In 2008, 150 people gathered for a wedding celebration in Baden-Württemberg, Germany. Three hours after ingestion of a variety of foods including pancakes filled with minced chicken, several guests exhibited symptoms of acute gastroenteritis such as vomiting, diarrhea, fever, and ague. Twelve guests were reported to have fallen ill, with nine of these seeking medical care in hospitals. At least four patients were admitted to the hospital and received inpatient treatment, among them a 2-year-old child and a woman in the 4th month of pregnancy. Within 24 h of the event, an investigative team collected a variety of samples including refrigerated leftovers, food in the storage unit of the caterer, nasal swabs of the caterer, as well as 21 environmental swabs. Five stool samples from patients were provided by the hospitals. Staphylococcus aureus isolates were gathered from eight samples, among them nasal swabs of the caterer, food samples, and one stool sample. Fourier transform-infrared spectroscopy was used for species identification and for primary clustering of the isolates in a similarity tree. The isolates were further characterized by spa typing and pulsed-field gel electrophoresis, and a DNA microarray was used to determine the presence/absence of genes involved in virulence and antimicrobial resistance. We were able to match an enterotoxigenic strain from the stool sample of a patient to isolates of the same strain obtained from food and the nasal cavity of a food handler. The strain produced the enterotoxin SEA and the toxic shock syndrome toxin-1, and was also found to exhibit the genes encoding enterotoxins SEG and SEI, as well as the enterotoxin gene cluster egc. This is one of only a few studies that were able to link a staphylococcal food poisoning outbreak to its source.

To assess the efficacy of single dose of octreotide and compare it with another antisecretory agent racecadotril in the management of acute infective diarrhea.A randomized control study was done in the Department of Medicine and Infectious Disease Hospital (Department of Preventive and Social Medicine) of SMS Medical College and Hospital. 150 patients with moderate to severe acute diarrheal illness needing hospitalization were randomly allotted into 3 categories of 50 patients each. The control group received only fluids and antibiotics, the racecadotril group received fluid, antibiotics and oral racecadotril at dose of 1.5 mg/kg three times a day and the octreotide group received octreotide (100 microgram stat) along with fluid and antibiotics. The following end points of the study were compared, namely- frequency, quantity and consistency of stools and fluid requirement per day.The mean (+/- SE) frequency of stools was significantly less (p < 0.001) from day 2 onwards in the octreotide group compared to the control and racecadotril group. Diarrhea stopped in half of the patients in the octreotide group by day 3. The consistency of stools changed significantly in the octreotide group (p < 0.001). No significant difference was seen between the racecadotril and control group (p > 0.05) in terms of the frequency and consistency of stools. The mean (+/- SE) quantity of stools was significantly decreased in the octreotide group (p < 0.001) on day 2 compared to the other two groups. The mean (+/- SE) quantity of fluid required was almost the same in all 3 groups on day 1 (p > 0.05) but it was significantly less in the octreotide group on day 2 (p < 0.001). No significant difference was seen with respect to the fluid requirement between the control and racecadotril group (p > 0.05).Patients who received single dose of octreotide fared better than those patients in control and racecadotril group in terms of frequency, quantity and consistency of stools passed. The fluid requirement was also less in octreotide group. However more trials need to be done to substantiate this finding before octreotide becomes a standard of therapy in acute infective diarrhea.

Cryptosporidium spp. is under recognized as an important pathogen causing diarrhea in children and HIV-infected individuals with associated high morbidity and mortality. In endemic areas, most symptomatic infections are in childhood and in immunocompromised adults. The immune status of the host plays a critical role in determining the severity of cryptosporidiosis. Infection is self-limited in immunocompetent hosts, but can be severe and persistent in the immunocompromised such as AIDS patients or malnourished children. Cryptosporidiosis in developing countries is a major cause of acute and persistent diarrhea in children and is associated with subsequent impairment in growth, physical fitness, and cognitive function. Despite recognition of the importance of immune status, the correlates of protective immunity in cryptosporidiosis in humans are poorly understood, and treatment modalities are limited.

To update the available evidence about zinc use for treating diarrhea in children and to assess its effect on the malnourished population, a subgroup that has not been fully explored in previous analyses.A systematic review was performed of randomized clinical trials that assessed children up to 5 years old with acute diarrhea who received zinc supplementation. Controls received a placebo or oral rehydration therapy. After searching the main databases, without language restrictions, two independent reviewers selected eligible studies, extracted the data, and assessed the risk of bias of included studies. Meta-analyses were calculated using Mantel-Haenszel or inverse variance random effects.Eighteen of 1 041 studies retrieved were included in the review (n = 7 314 children). Zinc was beneficial for reducing the duration of diarrhea in hours (mean difference [MD] = -20.12, 95% confidence interval [CI] = -29.15 to -11.09, I² = 91%). The effect was greater in malnourished children (MD = -33.17, 95% CI = -33.55 to -27.79, I² = 0%). Diarrhea prevalence on days 3, 5, and 7 was lower in the zinc group. The incidence of vomiting was significantly greater in the group that received zinc than in the control group. Included randomized controlled trials were of low risk of bias in most domains assessed.Oral zinc supplementation significantly decreases diarrhea duration and has a greater effect on malnourished children. Zinc supplementation seems to be an appropriate public health strategy, mainly in areas of endemic deficiencies.