Prognostic significance of serum cholesterol in nursing home men

Serum cholesterol was measured in 129 men (average age 70.6; range 41-96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base. Serum cholesterol was less than 150 mg/dl in 13% of the subjects, and was less than 160 mg/dl in 18%. Cholesterol greater than 280 mg/dl occurred in 8%. Serum cholesterol varied directly (p less than 0.02) with: body weight, serum albumin, serum total protein, serum sodium, ability to walk, and ability to feed oneself; and indirectly (p less than 0.02) with death rate, degree of functional dependence, and serum SGOT and LDH. Nursing home men with cholesterol less than 150 mg/dl had a death rate of 63% during the 14 months after the cholesterol analysis, compared to a death rate of 9% in men with cholesterol greater than 150 mg/dl (p less than 0.05). Death rate during the year after the analysis was 52% if cholesterol was below 160 mg/dl, compared to 7% if it was above this threshold (p less than 0.05).     

A phase I study to study arsenic trioxide with radiation and hyperthermia in advanced head and neck cancer.

PURPOSE: Arsenic trioxide [ATO] is a pluripotent drug with potentials to have pro-oxidant, angiogenesis inhibitor, flow inhibitor and radiation sensitizer properties. METHODS: The present study is a Phase I trial to assess the safety of ATO in advanced or recurrent head and neck cancer treated with radiation and hyperthermia. Patients received ATO at 10, 20 and 30 mg per week a day prior to hyperthermia. RESULTS: It was assumed that vascular collapse would be complete by 24 h. Administration of ATO at 20 mg was safe with no toxicity due to ATO. No amplification of toxicities due to radiation or hyperthermia was evident. Patients without prior treatment showed better response. A total of 11 patients were included in this Phase I study. CONCLUSIONS: Patients who received 30 mg of ATO weekly showed non-serious acute toxicities. No further escalation of dose was attempted.     

Allogeneic vaccination with a B7.1 HLA-A gene-modified adenocarcinoma cell line in patients with advanced non-small-cell lung cancer.

PURPOSE: To determine the safety, immunogenicity, and clinical response to an allogeneic tumor vaccine for non-small-cell lung cancer, we conducted a phase I trial in patients with advanced metastatic disease. PATIENTS AND METHODS: We treated 19 patients with a vaccine based on an adenocarcinoma line (AD100) transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated intradermally with 5 x 10(7) cells once every 2 weeks. Three vaccinations represented one course of treatment. If patients had complete response, partial response, or stable disease, they continued with the vaccinations for up to three courses (nine vaccinations). Immune response was assessed by a change between pre-study and postvaccination enzyme-linked immunospot frequency of purified CD8 T-cells secreting interferon-gamma in response to in vitro challenge with AD100. RESULTS: Four patients experienced serious adverse events that were unrelated to vaccine. Another four patients experienced only minimal skin erythema. All but one patient had a measurable CD8 response after three immunizations. The immune response of six surviving, clinically responding patients shows that CD8 titers continue to be elevated up to 150 weeks, even after cessation of vaccination. Overall, one patient had a partial response, and five had stable disease. Median survival for all patients is 18 months (90% CI, 7 to 23 months), with corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and 30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not bear a significant relation to response. CONCLUSION: Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination.     

Patellar tendon or hamstring graft anterior cruciate ligament reconstructions in patients aged above 50 years

Background:

The treatment of anterior cruciate ligament (ACL) injury consists of arthroscopic ACL reconstruction with patellar tendon or hamstring graft. Satisfactory results have been reported so far in the younger age group. Dilemma arises regarding the suitability of ACL reconstruction in patients aged 50 years and above. This retrospective analyses the outcome of ACL reconstruction in patients aged 50 years and above.

Materials and Methods:

55 patients aged 50 years and above presented to our institution with symptomatic ACL tear and were managed with arthroscopic reconstruction with patellar tendon/hamstring graft. 22 patients underwent ACL reconstruction with bone- patellar tendon-bone graft and the remaining 33 with a hamstring graft. Evaluation of functional outcome was performed using International Knee Documentation Committee (IKDC) and Lysholm scoring in the preoperative period, at the end of 1 year and at the final followup. Radiographic evaluation was performed using the Kellgren–Lawrence grading system.

Results:

The mean preoperative IKDC score was 39.7 ± 3.3. At the end of 1-year following the operation, the mean IKDC score was 73.6 ± 4.9 and at the final followup was 67.8 ± 7.7. The mean preoperative Lysholm score was 40.4 ± 10.3. At the end of 1-year following the intervention, the mean Lysholm score was 89.7 ± 2.1 and at final followup was 85.3 ± 2.5. Overall, 14 out of 42 patients who underwent radiographic assessment showed progression of osteoarthritis changes at the final followup after the intervention.

Conclusion:

In our study, there was a statistically significant improvement in the IKDC and Lysholm scores following the intervention. There was a slight deterioration in the scores at the final followup but the overall rate of satisfaction was still high and most of the patients were able to do their routine chores and light exercises suitable for their age group. Around one-third of patients show progression of radiographic changes in the postoperative period and this requires long term evaluation.     

Laparoscopic Transplantation Following Transvaginal Insertion of the Kidney: Description of Technique and Outcome

Laparoscopic kidney transplantation (LKT) is well accepted modality of treatment for ESRD patients at our center. Usually, the kidney is inserted through small Pfannenstiel incision. With the permission of the Internal Review Board, we carried out LKT in eight female recipients following insertion of the kidney through the vagina. The kidney was procured by the retroperitoneoscopic approach. Antibiotic prophylaxis was given. All cases were carried out successfully with immediate graft function and 100% graft and patient survival at 1 year of follow‐up. Estimated glomerular filtration rate at 1 month and 1 year was similar to eight randomly selected female recipients who underwent open kidney transplantation (OKT). No analgesia was required in seven out of eight patients after the 3rd postoperative day. In summary, vaginal insertion of kidney and LKT is safe and feasible in a selected group of patients. It is associated with better analgesia and has similar allograft function as compare to OKT.     

Polyacrylamide hydrogel (Bulkamid®) for stress urinary incontinence in women: a systematic review of the literature

Introduction and hypothesis

Polyacrylamide hydrogel (PAHG, Bulkamid®) is one of several injectable agents currently used for the treatment of women with urinary stress incontinence. Although bulking agents appear to have lower efficacy rates compared to other surgical treatments, current evidence based on large prospective or comparative studies as well as systematic reviews is limited. The purpose of this study was to conduct a systematic review on the efficacy of PAHG in the treatment of female patients with stress urinary incontinence with regard to reproducibility, feasibility, safety and clinical outcome.

Methods

We searched MEDLINE (1966–2015), Scopus (2004–2015), POPLINE (1974–2015) and ClinicalTrials.gov (2008–2015) along with reference lists of electronically retrieved studies. Observational studies, prospective, retrospective and randomized controlled studies were included. Two reviewers independently selected studies, assessed the risk of bias and tabulated data to structured forms.

Results

We included 8 studies, which enrolled a total of 767 patients who received treatment with PAHG. We found that 186 of 767 women (24.3 %, range 12–35 %) required reinjection in order to achieve adequate efficacy. The most frequent adverse effects were pain at the site of injection (4–14 %) and urinary tract infections (3–7 %). Both the number of incontinence episodes/24 h and the number of ml/24 h were significantly reduced 1 year following treatment and the quality of life of patients was significantly improved.

Conclusions

PAHG is a safe intervention for treating women with stress urinary incontinence, but repeat injections are often required. Further research is mandated in the field in order to compare its efficacy to other bulking agents.

     

Discovery of Thienoimidazole-Based HCV NS5A Genotype 1a and 1b Inhibitors

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PhageLeads: Rapid Assessment of Phage Therapeutic Suitability Using an Ensemble Machine Learning Approach

The characterization of therapeutic phage genomes plays a crucial role in the success rate of phage therapies. There are three checkpoints that need to be examined for the selection of phage candidates, namely, the presence of temperate markers, antimicrobial resistance (AMR) genes, and virulence genes. However, currently, no single-step tools are available for this purpose. Hence, we have developed a tool capable of checking all three conditions required for the selection of suitable therapeutic phage candidates. This tool consists of an ensemble of machine-learning-based predictors for determining the presence of temperate markers (integrase, Cro/CI repressor, immunity repressor, DNA partitioning protein A, and antirepressor) along with the integration of the ABRicate tool to determine the presence of antibiotic resistance genes and virulence genes. Using the biological features of the temperate markers, we were able to predict the presence of the temperate markers with high MCC scores (>0.70), corresponding to the lifestyle of the phages with an accuracy of 96.5%. Additionally, the screening of 183 lytic phage genomes revealed that six phages were found to contain AMR or virulence genes, showing that not all lytic phages are suitable to be used for therapy. The suite of predictors, PhageLeads, along with the integrated ABRicate tool, can be accessed online for in silico selection of suitable therapeutic phage candidates from single genome or metagenomic contigs.