Local Immune Response Predicts Survival in Patients with Thick (T4) Melanomas

Background

Tumor infiltrating lymphocytes (TIL) and histological regression in primary melanoma are generally considered indicators of the local immune response but their roles as prognostic factors have been variably reported. We examined the prognostic role of these variables in patients with high risk (T4) primary melanomas in a large series of patients with long-term follow-up.

Methods

From a prospectively maintained cohort of patients diagnosed between 1971 and 2004, 161 patients were retrospectively identified with primary thick melanomas (>4 mm), no clinical evidence of regional nodal disease (RND) at diagnosis and complete histopathologic data. Univariate and multivariate Cox regression models were performed to identify clinical and histopathologic predictors of disease-specific survival (DSS) and to identify subgroups with differential survival.

Results

Factors significantly associated with decreased DSS by univariate analysis included male gender, age ≥ 60 years, axial anatomic location, presence of ulceration, RND, absence of TIL, and presence of regression. In the final multivariate model, TIL and regression, as interacting variables, and RND status remained significantly associated with DSS. In the presence of TIL, concomitant regression was associated with significantly worse survival (p ≤ 0.0001). In the absence of TIL, there was no effect of regression on survival (p = 0.324).

Conclusions

Primary TIL and regression status and RND status are independently associated with melanoma-specific survival in patients with T4 melanomas; presence of TIL in the primary melanoma with concomitant radial growth phase regression is associated with a poor prognosis and may reflect an ineffective local regional immune response.     

Sexual function in patients presenting to a urogynecology practice

The purpose of this study was to evaluate sexual function in women referred to a urogynecology practice. All new patients were mailed an optional female sexual function index (FSFI) in conjunction with their history forms; other sexual function information was obtained during the physician interview. Over 6 months, four hundred fifty new patients were enrolled. Of these, 243 (54%) were not sexually active. Reasons listed for sexual inactivity included partner problems/no partner (32%), low desire (14%), prolapse (10%), and pain (10%). There were several differences between sexually active and non-sexually active participants; however, after a multivariate analysis, only age, marital status, and stage/grade 1–2 of prolapse remained significant. One hundred nine sexually active patients completed the FSFI; the majority was sexually active two to four times per month. Female sexual dysfunction was noted in 70 (64%) patients. Lowest scores were noted for the domain of desire, followed by arousal, orgasm, lubrication, satisfaction, and pain. Reduced frequency of intercourse was the only factor significantly associated with dysfunction. Ninety-four percent were not embarrassed by the survey. Overall, sexual inactivity is common in patients presenting for urogynecologic care. Those that are sexually active report low rates of sexual activity and high rates of sexual dysfunction. Most sexually active patients will accept a sexual function questionnaire as part of their routine assessment.This research was presented at the American College of Obstetricians and Gynecologists annual clinical meeting, May 10, 2005, San Francisco, CA, USA.     

Impact of Gastric Banding on Plasma Adiponectin Levels

Background: Several endocrine abnormalities are reported in obesity. In an earlier study, we found that the changes in BMI following laparoscopic adjustable gastric banding (LAGB) were associated with changes in hormone profiles such as insulin and proinsulin. In the current study, we explored the changes in plasma adiponectin levels in morbidly obese subjects who lost abundant weight following LAGB. Methods: 23 adult morbidly obese patients (15 females), aged 21-56 years, were studied. Blood samples were collected before, and 6 and 14 months after LAGB. The plasma adiponectin levels were determined by commercial kit (B-Bridge International, Inc). Statistical analysis was based on one-way repeated measures ANOVA, followed by Student-NewmanKeuls post-hoc test. Regression model was used to look for predictors of adiponectin change after LAGB. Results: Mean BMI before surgery was 46.04±4.44 kg/m², and decreased significantly by 18% 6 months after surgery to 37.67±4.47 kg/m². BMI further decreased by 32% 14 months after surgery to a mean of 31.30±4.65 kg/m² (P =.000). The mean adiponectin level before surgery was 3997±1766 μg/ml, and increased significantly by 16% to 4763±1776 μg/ml 6 months after surgery, and to 6336±3292 μg/ml (37%) 14 months after surgery. Although BMI persistently decreased, while adiponectin persistently increased, BMI did not correlate with adiponectin. Conclusion: In morbidly obese patients who underwent LAGB, adiponectin levels persistently increased, probably due to the reduction of visceral fat mass. Adiponectin plasma increase was correlated with proinsulin levels prior to the surgery. The interaction between adiponectin, proinsulin and BMI change in morbid obesity merits further investigation.     

The heart of children with steroid-resistant nephrotic syndrome: is it all podocin?

Mutations in the gene NPHS2 encoding podocin are responsible for a recessive form of steroid-resistant nephrotic syndrome (SRNS). The common phenotype is of massive proteinuria in early childhood that tends to progress to end-stage renal failure. Extrarenal manifestations have not been described. Twenty-two children with SRNS from six unrelated Arab families were found to be homozygous for the R138X mutation in NPHS2. Eighteen patients underwent cardiac evaluation at diagnosis of SRNS while they had normal BP and preserved renal function. Cardiac anomalies were detected in 16 (89%) children: Left ventricular hypertrophy in eight, pulmonary stenosis in six, discrete subaortic stenosis in two, and Ebstein anomaly and ventricular septal defect in one each. The remaining four affected individuals were assessed only once they had end-stage renal failure. They had severe left ventricular hypertrophy and experienced repeated episodes of heart failure. Two control groups were equally evaluated. The first consisted of 37 siblings without nephrotic syndrome, of whom only one carrier had a cardiac defect (P < 0.001). None of the second group, which included 22 children with persistent nephrotic syndrome as a result of other causes, had a cardiac anomaly (P < 0.001). Cardiac disorders in homozygotes for mutations in NPHS2 cannot be attributed to an association by chance or to a state of persistent nephrotic syndrome. Because human podocin mRNA is expressed in fetal heart, it is speculated that it may have a role in normal cardiac development. Cardiac evaluation is recommended at the time of diagnosis of SRNS due to mutations in podocin.     

A truncated polycystin-2 protein causes polycystic kidney disease and retinal degeneration in transgenic rats

The cloning of the PKD1 and PKD2 genes has led to promising new insight into the mechanisms that are responsible for cyst development in patients with autosomal dominant polycystic kidney disease. Although the dominant pattern of inheritance would argue for haploinsufficiency, a gain of function, or a dominant negative mechanism, there is good evidence that autosomal dominant polycystic kidney disease behaves like a recessive disease on a cellular level (two-hit mechanism of cystogenesis). For testing of whether other pathomechanisms in addition to the two-hit hypothesis can explain cyst formation, two transgenic rat lines that contain a truncated human polycystin-2 cDNA were generated. The protein product lacks almost the entire COOH-terminus and mimics mutations that frequently are found in patients. The transgene-encoded mRNA could be detected in multiple tissues of both transgenic lines, with the highest expression in the kidney. Both lines present with renal cysts that originate predominantly from the proximal tubule; in the tubular epithelial cells, the epitope-tagged mutant protein was detected in the brush border and in primary cilia. Further evidence of the involvement of primary cilia stems from the finding of retinal degeneration in the transgenic rats and from the fact that stably transfected LLC-PK(1) cells that inducibly produced the truncated polycystin-2 protein elaborated shorter cilia. Other experimental approaches, such as a knock-in strategy, will be necessary to validate these results, but this is the first preliminary evidence that cyst formation is due not only to somatic mutations.     

Technique and results of Achilles tendon detachment and reconstruction for insertional Achilles tendinosis

BACKGROUND: Insertional Achilles tendinosis is a clinical entity that commonly occurs with other posterior heel disorders such as retrocalcaneal bursitis, Haglund deformity, intratendinous ossification and pretendinous bursitis. Complete detachment and reconstruction of the Achilles tendon was evaluated as a method of treatment for this condition. METHODS: Seventy-five patients (81 heels) were treated over a 5-year period for chronic insertional Achilles tendinosis. These were divided in two groups: a nondetached group (26 patients, 31 heels, average age 55 years) included all patients with debridement of the Achilles tendon with no or partial detachment of the tendon, and a detached group (49 patients, 50 heels, average age 56.1 years) that included all patients with complete detachment, debridement, and reattachment with suture anchors of the Achilles tendon associated with proximal V-Y lengthening of the proximal aponeurosis. Sixty-one patients (65 heels) were contacted for an interview questionnaire, 22 patients from the nondetached group (26 heels) and 39 patients from the detached group (39 heels). The average followup for the nondetached group was 47 months and for the detached group 33 months. Items evaluated included pain, activity limitation, gait change, walking distance, return to sport or work, and level of satisfaction. RESULTS: No statistically significant differences were noted in relation to any of the items evaluated. In the nondetached group, the satisfaction rate was 92%, and 8% were dissatisfied. In the detached group, 74% were completely satisfied and 18% were satisfied with reservations. Eight percent were dissatisfied. Complications included minor wound dehiscence (one in the nondetached, five in the detached group), wound infection (one in the nondetached group, two in the detached group) and sural neuritis (two in the detached group). CONCLUSIONS: Complete detachment of the Achilles tendon and reattachment with suture anchors and a proximal V-Y lengthening was a reliable and effective method of treatment for severe chronic insertional Achilles tendinosis as was debridement of the tendon insertion without detachment for less severe involvement.     

White paper on antimicrobial stewardship in solid organ transplant recipients

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.     

Trends and risk factors for mortality in elderly burns patients: A retrospective review

IntroductionThe elderly experience higher mortality rates and poorer outcomes compared to younger burn survivors with similar injuries.MethodsThis epidemiological study reviewed records of all admitted elderly burn patients collected from five burns facilities in Israel between 1997–2016. Collected data was limited to the population aged 20+, focused on the population aged 60+.ResultsMortality rates for elderly patients increased with TBSA and increases with age. Regression analyses demonstrated a decrease in mortality of 2.9% (p = 0.013) per 5 years, an overall decrease of 11.6% over the 20-year study period, with the decline more significant for older age groups. This decrease in mortality was much larger than that observed for all burns patients over this period. The most common cause of injury in the elderly population was fire, with mortality rate highest for this cause. There was no effect of gender on mortality rate. Mortality increased when smoke inhalation was present for TBSA<20%, with mortality unaffected by the presence of smoke inhalation for higher TBSA. The need for surgery correlates with high mortality rates.ConclusionThis study identified key factors that impact mortality and demonstrated a large decrease in mortality in the elderly patients over the study period.