A Phase I study of 9-nitrocamptothecin given concurrently with capecitabine in patients with refractory,metastatic solid tumors

BACKGROUND: 9-Nitrocamptothecin (9-NC) is an orally available camptothecin analog with antineoplastic activity that results from the inhibition of DNA topoisomerase I. Previous studies have suggested that it has significant clinical efficacy. The primary toxicities of 9-NC include gastrointestinal upset, cystitis, and myelosuppression at the maximum tolerated dose (MTD) of 1.5 mg/m(2) per day. Capecitabine is a prodrug of 5-fluorouracil that is approved for use in patients with metastatic breast carcinoma and colorectal carcinoma, and it offers the convenience of oral administration. This trial examined the combination of these two oral agents in patients with metastatic solid tumors. METHODS: Capecitabine was administered twice daily at a total daily dose of 1300 mg/m(2) per day for 14 days followed by a 1-week break. 9-NC was taken daily 5 days per week for 2 weeks in a dose-escalation scheme. The starting dose was 0.5 mg/m(2) per day, and cohorts of 3 patients were enrolled until the dose level reached 1.25 mg/m(2) per day. RESULTS: Twenty-one patients were evaluable for toxicity and response, and nausea and emesis were the dose-limiting toxicities. Despite antiemetic prophylaxis with 5-hydroxytryptamine-3 antagonists, 2 of 3 patients at the 1.0 mg/m(2) per day dose level had Grade 2-3 nausea; while at the MTD of 0.75 mg/m(2) per day, 3 of 14 patients had Grade > or = 2 nausea. The incidence of hand-foot syndrome, stomatitis, diarrhea, and myelosuppression did not exceed that expected with capecitabine alone, suggesting that 9-NC does not exacerbate these side effects. No objective responses were seen. Stable disease was observed in 9 patients (43%) with a median duration of 11 weeks, including 3 patients with responses that lasted from 20 weeks to 40 weeks. CONCLUSIONS: The combination of 9-NC and capecitabine with the current schedule was limited in dose by nausea and had minimal clinical efficacy in a group of patients with refractory solid tumors.     

Hypothyroidism and levothyroxine therapy following bariatric surgery: a systematic review,meta-analysis,network meta-analysis,and meta-regression

BackgroundMany health benefits of bariatric surgery are known and well-studied, but there is scarce data on the benefits of bariatric surgery on the thyroid function.ObjectiveWe aimed to make a meta-analysis regarding the impact of bariatric surgery on thyroid-stimulating hormone (TSH) levels, levothyroxine dose, and the status of subclinical hypothyroidism.SettingSystematic review and meta-analysis.MethodsPubMed, EMBASE, and Cochrane Library were searched up to December 2020 for relevant clinical studies. Random-effects model was used to pool results. Network meta-analysis was performed, incorporating direct and indirect comparisons among different types of bariatric surgery. Meta-regression analysis was performed to evaluate the impact of moderator variables on TSH levels and required levothyroxine dose after surgery. We followed the PRISMA guidelines for data selection and extraction. PROSPERO registry number: CRD42018105739.ResultsA total of 28 studies involving 1284 patients were included. There was a statistically significant decrease in TSH levels after bariatric surgery (mean difference = ?1.66 mU/L, 95%CI [?2.29, ?1.03], P < .0001). In meta-regression analysis, we found that the following moderator variables: length of follow-up, mean age, baseline TSH, and preoperative thyroid function, could explain 1%, 43%, 68%, and 88% of the between-study variance, respectively. Furthermore, subclinical hypothyroidism was completely resolved in 87% of patients following bariatric surgery. In addition, there was a statistically significant decrease of levothyroxine dose in frank hypothyroid patients following bariatric surgery (mean difference = ?13.20 mcg/d, 95%CI [?19.69, ?6.71]). In network meta-analysis, we found that discontinuing or decreasing levothyroxine dose was significant following Roux-en-Y gastric bypass, 1 anastomosis gastric bypass, and sleeve gastrectomy, (OR = 31.02, 95%CI [10.34, 93.08]), (OR = 41.73, 95%CI [2.04, 854.69]), (OR = 104.03, 95%CI [35.79, 302.38]), respectively.ConclusionsBased on our meta-analysis, bariatric surgery is associated with the resolution of subclinical hypothyroidism, a decrease in TSH levels, and a decrease in levothyroxine dose.     

Neonatal blood glucose concentrations in caesarean and vaginally delivered term infants

Background: Little is known about the glucose concentrations at and after birth of infants delivered by caesarean section (CS), when compared with infants born vaginally (VD). Aim: To compare venous cord blood glucose concentrations of term infants born after elective CS to infants born by VD. We studied the null hypothesis that mode of delivery does not affect neonatal blood glucose values. Methods: We compared cord blood glucose concentrations in healthy term infants born after VD (n = 16) or by elective CS (n = 21). Glucose concentrations were obtained immediately at birth from the umbilical cord. Kruskal–Wallis was used to compare glucose concentrations and demographic variables between the groups. Results: Gestational age was 39.6 ± 0.8 weeks in VD group vs. 38.7 ± 0.9 weeks in CS group, and birthweight was 3359 ± 494 vs. 3500 ± 528 g. Cord blood glucose concentration was higher in VD (81.3 ± 16.9 mg/dL) than CS infants (70.3 ± 9.7 mg/dL, p = 0.039). The change in blood glucose concentration over the first 2‐h of life differed significantly between the two groups, being an increase in CS versus a decrease in VD infants (?3.5 ± 15.2 vs. ?15.4 ± 24.6 mg/dL, p = 0.013). Conclusions: Glucose concentrations in VD infants are higher than in infants born by elective CS without labour.     

Gammopathy with proximal motor axonopathy simulating motor neuron disease

We report a 38-year-old man with a pure motor syndrome and IgM gammopathy leading to flaccid quadriplegia. Improvement followed treatment with dexamethasone, cyclophosphamide, and plasmapheresis, but he died of pulmonary embolism. At autopsy, he had a proximal motor axonopathy with lymphocytic infiltration of ventral roots. Proximal motor neuropathy may masquerade as motor neuron disease. The association with gammopathy and response to treatment suggest that patients with motor neuron disease should be routinely screened for serum protein abnormalities.     

Responsiveness of pituitary hGH to GRH1-44 in juveniles with obesity

The response of plasma hGH to an iv bolus injection of GRH1-44 (1 microgram/kg) was studied in 14 obese juveniles with a mean overweight of 4.7 +/- 0.05 standard deviation score (SDS). Two patterns of response were observed: in all 7 adolescents with 'simple' obesity not related to any particular disorder (group A) the response was good (a mean of 11.8 +/- 2.4 ng/ml) whereas in 6 of the 7 juveniles suffering from syndromes associated with obesity (group B) the response was poor (a mean of 3.2 +/- 1.4 ng/ml). This divergence in response could not be related to a difference in the degree of overweight. These results indicate that in group B with syndromes associated with obesity there may also be a pituitary impairment in addition to the hypothalamic defect.     

Systemic Exposure to Irradiated Apoptotic Cells Induces Autoantibody Production

During apoptotic cell death, cell surface ligands initiate phagocytosis of the dying cell. Clearance of these apoptotic cells is thought to occur without an immune response. Since a number of autoantigens are located at the cell surface or within apoptotic blebs, we examined whether exposure of mice to syngeneic apoptotic cells by the intravenous route could induce autoantibody production. Normal mice injected with syngeneic apoptotic thymocytes developed antinuclear autoantibodies and anticardiolipin and anti-ssDNA antibodies. The autoantibody levels were generally lower than those observed in MRL/Fas^lpr mice and were transient. Surprisingly, six out of six immunized mice demonstrated immunoglobulin G deposition in the glomeruli several months after immunization. These findings indicate that systemic exposure to apoptotic cells can induce an immune response in normal mice, and may help to explain antigen selection and initiation of the immune response in diseases characterized by increased rates of apoptosis such as AIDS and, possibly, systemic lupus erythematosus.     

Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections

Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii. In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems.     

Modified Trochanteric Slide for Complex Hip Arthroplasty : Clinical Outcomes and Complication Rates

The sliding trochanteric osteotomy preserves vastus lateralis continuity with the osteotomized greater trochanter (GT) and the abductors. The modified trochanteric sliding osteotomy (MTSO) also preserves the posterior capsule and external rotators to reduce the risk of dislocations. The purpose of this study was to evaluate our clinical and radiographic results of the MTSO exposure. Eighty-three MTSOs were reviewed. Follow-up range was 12 to 126 months. Seventy osteotomies (84.4%) healed with bony union, 9 (10.8%) had fibrous union, and 4 (4.8%) had nonunion. There was no correlation between the width of the osteotomy, intraoperative fragmentation of the GT, or the type of femoral component and the rate of union. Six (7.2%) patients developed a new abductor lurch. Patients with union of the GT had 2.8% of a lurch, and patients with either fibrous union or nonunion had a 30.7% of a lurch (P < .05). There were 4 (4.8%) postoperative dislocations. The benefits of MTSO have been well described, and this study provides evidence of an acceptably low complication rate.