Safety, feasibility, and effect of an enhanced nutritional support pathway including extended preoperative and home enteral nutrition in patients undergoing enhanced recovery after esophagectomy: a pilot randomized clinical trial.

The aims of this pilot study are to evaluate the feasibility, safety, and effectiveness of conducting an enhanced nutritional support pathway including extended preoperative nutritional support and one month home enteral nutrition (HEN) for patients who underwent enhanced recovery after esophagectomy. We implemented extended preoperative nutritional support and one month HEN after discharge for patients randomized into an enhanced nutrition group and implemented standard nutritional support for patients randomized into a conventional nutrition group. Except the nutritional support program, both group patients underwent the same standardized enhanced recovery after surgery programs of esophagectomy based on published guidelines. Patients were assessed at preoperative day, postoperative day 7 (POD7), and POD30 for perioperative outcomes and nutritional status. To facilitate the determination of an effect size for subsequent appropriately powered randomized clinical trials and assess the effectiveness, the primary outcome we chose was the weight change before and after esophagectomy. Other outcomes including body mass index (BMI), lean body mass (LBM), appendicular skeletal muscle mass index (ASMI), nutrition-related complications, and quality of life (QoL) were also analyzed. The intention-to-treat analysis of the 50 randomized patients showed that there was no significant difference in baseline characteristics. The weight (-2.03 ± 2.28 kg vs. -4.05 ± 3.13 kg, P = 0.012), BMI (-0.73 ± 0.79 kg/m2 vs. -1.48 ± 1.11 kg/m2, P = 0.008), and ASMI (-1.10 ± 0.37 kg/m2 vs. -1.60 ± 0.66 kg/m2, P = 0.010) loss of patients in the enhanced nutrition group were obviously decreased compared to the conventional nutrition group at POD30. In particular, LBM (48.90 ± 9.69 kg vs. 41.96 ± 9.37 kg, p = 0.031) and ASMI (7.56 ± 1.07 kg/m2 vs. 6.50 ± 0.97 kg/m2, P = 0.003) in the enhanced nutrition group were significantly higher compared to the conventional nutrition group at POD30, despite no significant change between pre- and postoperation. In addition, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scores revealed that enhanced nutritional support improved the QoL of patients in physical function (75.13 ± 9.72 vs. 68.33 ± 7.68, P = 0.009) and fatigue symptom (42.27 ± 9.93 vs. 49.07 ± 11.33, P = 0.028) compared to conventional nutritional support. This pilot study demonstrated that an enhanced nutritional support pathway including extended preoperative nutritional support and HEN was feasible, safe, and might be beneficial to patients who underwent enhanced recovery after esophagectomy. An appropriately powered trial is warranted to confirm the efficacy of this approach.

[Characterization of N-linked glycosylation sites on envelope proteins of simian/human immunodeficiency virus in peripheral blood of Chinese rhesus macaques during acute infection].

Objective: To investigate the number and distribution of N-linked glycosylation sites of simian/human immunodeficiency virus envelope proteins(SHIVSF162P3)and SHIV transmission. Methods: Two female adult Chinese rhesus macaques(4 years old)were intravenously inoculated with 300 TCID50 SHIVSF162P3. The macaques weighed 4 and 5 kg and were identified as Rh1 and Rh2. We collected plasma samples at days 3, 7, 10, 14, 17, 21, 24, 28, 35, 42, 49, 56, 63, 70 and 77 post-challenge. Subsequently, we monitored plasma viral load by real-time PCR after viral RNA isolation and cDNA synthesis. We amplified the full-length envelope gene by single genome amplification(SGA)at days 7, 14, 28 and 77. BioEdit, MEGA, and the HIV Databases were used to analyze envelope sequences. Sequence diversity and N-linked glycosylation sites were compared between virus stock and plasma viruses of the two macaques. Results: A total of 55 env sequences were obtained from virus stock and their average pairwise distances were(0.166 6± 0.096 3)%. Viral loads peaked at 7.68 and 7.49 log10 copies/ml at day 10 and reached the set point at day 42(4.27 and 4.81 log10 copies/ml). The percentages of envelope sequences containing 25 potential N-linked glycosylation sites(PNGSs)were 83%(20/24)and 94%(29/31)in Rh1 and Rh2, respectively, at day 7; these were significantly higher than the proportion in SHIVSF162P3 stock(49%(27/55)). Viral diversity after infection increased with time whereas the proportion of sequences containing 25 PNGSs decreased and sequences containing 27 PNGSs gradually increased. In Rh1, the percentage of sequences containing 27 PNGSs increased to 29% at day 28 and reached 35% at day 77 in Rh2. By analyzing the number of PNGSs in the V1-V5 regions, we found that PNGS variation mainly occurred in the V4 loop. Compared with sequences containing 27 PNGSs, a seven amino acid(TWNNTIG)deletion was found in the V4 loop, which resulted in a loss of two PNGSs at positions 392 and 396. Conclusion: Low glycosylation of the SHIVSF162P3 V4 loop may facilitate spread of the SHIV virus whereas viruses with highly glycosylated V4 loops showed replication advantages after infection.

Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study.

Deep brain stimulation (DBS) of the thalamic centromedian/parafascicular (CM-Pf) complex has been reported as a promising treatment for patients with severe, treatment-resistant Tourette syndrome (TS). In this study, safety and clinical outcomes of bilateral thalamic CM-Pf DBS were reviewed in a series of 12 consecutive patients with medically refractory TS, 11 of whom met the criteria of postsurgical follow-up at our institution for at least 2 months. Five patients were followed for a year or longer. Consistent with many patients with TS, all patients had psychiatric comorbidities. Tic severity and frequency were measured by using the Yale Global Tic Severity Scale (YGTSS) over time (average, 26 months) in 10 subjects. One patient was tested at 2-week follow-up only and thus was excluded from group YGTSS analysis. Final YGTSS scores differed significantly from the preoperative baseline score. The average (n=10) improvement relative to baseline in the total score was 54% (95% CI, 37-70); average improvement relative to baseline in the YGTSS Motor tic, Phonic tic, and Impairment subtests was 46% (95% CI, 34-64), 52% (95% CI, 34-72), and 59% (95% CI, 39-78), respectively. There were no intraoperative complications. After surgery, 1 subject underwent wound revision because of a scalp erosion and wound infection; the implanted DBS system was successfully salvaged with surgical revision and combined antibiotic therapy. Stimulation-induced adverse effects did not prevent the use of the DBS system, although 1 subject is undergoing a trial period with the stimulator off. This surgical series adds to the literature on CM-Pf DBS and supports its use as an effective and safe therapeutic option for severe refractory TS.

Hemoglobin decline in chemotherapy patients prior to and after policy changes affecting use of erythropoiesis-stimulating agents: 2006-2009.

OBJECTIVE: Since 2007, the use of erythropoiesis-stimulating agents (ESAs) to treat anemia in cancer patients receiving chemotherapy has been increasingly restricted in the USA. This study assessed hemoglobin (Hb) decline over time among chemotherapy patients. METHODS: Episodes of chemotherapy care were identified in a large US-oncology electronic medical record database; weekly Hb levels were computed in the first 8 weeks. Unadjusted and adjusted proportions of patient-weeks with Hb decline>1 g/dl (i.e. representing clinically significant decline) within 1 or 2 weeks were analyzed. RESULTS: Between 2006 and 2009, unadjusted proportions of patient-weeks with Hb decline>1 g/dl increased (1-week, from 12.7% to 14.9%; 2-week, from 19.3% to 26.3%). Adjusted 1-week proportions in 2007 were similar to 2006, but increased in 2008 (odds ratio [OR] 1.135; 95% confidence intervals [CI] 1.067, 1.208) and in 2009 (OR 1.235; 95% CI 1.094, 1.395). Adjusted 2-week proportions had the same pattern. CONCLUSIONS: Since restrictions on ESA use were introduced in the USA, more patients have experienced a clinically significant Hb decline after chemotherapy initiation. Initiating anemia therapy at the earliest indicated opportunity may help reduce the risk of such declines.

TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells.

BACKGROUND: The full mechanism of action of isotretinoin [13-cis retinoic acid (13-cis RA)] in treating acne is unknown. 13-cis RA induces key genes in sebocytes that are involved in apoptosis, including Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL). OBJECTIVES: In this study, we investigated the role of 13-cis RA-induced TRAIL within SEB-1 sebocytes. METHODS: Using 13-cis RA and recombinant human TRAIL (rhTRAIL) protein, we assessed induction of TRAIL and apoptosis in SEB-1 sebocytes, normal keratinocytes and patient skin biopsies. RESULTS: Treatment with rhTRAIL protein increased TUNEL-positive staining in SEB-1 sebocytes. TRAIL siRNA significantly decreased the percentage of TUNEL-positive SEB-1 sebocytes in response to 13-cis RA treatment. Furthermore, TRAIL expression increased in the skin of patients with acne after 1 week of isotretinoin therapy compared with baseline. TRAIL expression localized within sebaceous glands. Unlike sebocytes, TRAIL protein expression was not increased in normal human epidermal keratinocytes in response to 13-cis RA, nor did rhTRAIL induce apoptosis in keratinocytes, suggesting that TRAIL is key in the sebocyte-specific apoptotic effects of 13-cis RA. CONCLUSIONS: Taken together, our data suggest that TRAIL, like the neutrophil gelatinase-associated lipocalin, is involved in mediating 13-cis RA apoptosis of sebocytes.

Isotretinoin increases skin-surface levels of neutrophil gelatinase-associated lipocalin in patients treated for severe acne.

BACKGROUND: A clear-cut need exists for safe and effective alternatives to the use of isotretinoin in severe acne. Lack of data regarding the specifics of isotretinoin's mechanism of action has hampered progress in this area. Recently, the protein neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a mediator of the apoptotic effect of isotretinoin on sebocytes. OBJECTIVES: To establish further the clinical relevance of NGAL and to elucidate the factors that induce NGAL expression in sebocytes. METHODS: Methods were developed to isolate and quantify skin-surface levels of NGAL from normal subjects and patients with acne undergoing treatment with isotretinoin. RESULTS: Patients with acne were found to have higher skin levels of NGAL compared with normal subjects. Studies in SEB-1 sebocytes indicate that NGAL expression is increased in response to Propionibacterium acnes and interleukin (IL)-1ß. In patients, isotretinoin increases NGAL levels by 2·4-fold on the skin surface and this increase precedes decreases in sebum and P. acnes counts. CONCLUSIONS: These data support the hypothesis that NGAL is an important mediator of the early effects of isotretinoin on the sebaceous glands and provide insights into the mechanisms that regulate NGAL expression in the skin.

Effect of dimethyl sulfoxide on cytosolic calcium in cultured rat hepatocytes injured by D-galactosamine.

D-galactosamine (Gal 0.5 mmol.L-1) made lactate dehydrogenase (LDH) leakage from the hepatocytes in monolayer-culture increase by 50%, Dimethyl sulfoxide (Me2SO 2% vol/vol) decreased the LDH leakage (P less than 0.05). The cytosolic free Ca2+ concentration ([Ca2+]c) of rat hepatocytes exposed to Gal 4 mmol.L-1 for 90 min in suspension culture increased about 2-fold (P less than 0.01). Me2SO (2%) antagonized this [Ca2+]c-increasing effect of Gal. These results verified directly that the [Ca2+]c of hepatocytes was increased in the early stage of Gal-induced hepatotoxicity, and suggested that the prevention or lightening of the disturbance in intracellular Ca2+ homeostasis may be, at least, one of the mechanisms of the protective action of Me2SO against Gal-induced hepatocyte injury.