Regulation of Immune Function by the Lymphatic System in Lymphedema

The lymphatic vasculature has traditionally been thought to play a passive role in the regulation of immune responses by transporting antigen presenting cells and soluble antigens to regional lymph nodes. However, more recent studies have shown that lymphatic endothelial cells regulate immune responses more directly by modulating entry of immune cells into lymphatic capillaries, presenting antigens on major histocompatibility complex proteins, and modulating antigen presenting cells. Secondary lymphedema is a disease that develops when the lymphatic system is injured during surgical treatment of cancers or is damaged by infections. We have used mouse models of lymphedema in order to understand the effects of chronic lymphatic injury on immune responses and have shown that lymphedema results in a mixed T helper cell and T regulatory cell (Treg) inflammatory response. Prolonged T helper 2 biased immune responses in lymphedema regulate the pathology of this disease by promoting tissue fibrosis, inhibiting formation of collateral lymphatics, decreasing lymphatic vessel pumping capacity, and increasing lymphatic leakiness. Treg infiltration following lymphatic injury results from proliferation of natural Tregs and suppresses innate and adaptive immune responses. These studies have broad clinical relevance since understanding how lymphatic injury in lymphedema can modulate immune responses may provide a template with which we can study more subtle forms of lymphatic injury that may occur in physiologic conditions such as aging, obesity, metabolic tumors, and in the tumor microenvironment

Surgical offloading procedures for diabetic foot ulcers compared to best non-surgical treatment: a study protocol for a randomized controlled trial

Abstract Background Diabetic foot ulcers are frequently related to elevated pressure under a bony prominence. Conservative treatment includes offloading with orthopaedic shoes and custom made orthotics or plaster casts. While casting in plaster is usually effective in achieving primary closure of foot ulcers, recurrence rates are high. Minimally invasive surgical offloading that includes correction of foot deformities has good short and long term results. The surgery alleviates the pressure under the bony prominence, thus enabling prompt ulcer healing, negating the patient’s dependence on expensive shoes and orthotics, with a lower chance of recurrence. The purpose of this protocol is to compare offloading surgery (percutaneous flexor tenotomy, mini-invasive floating metatarsal osteotomy or Keller arthroplasty) to non-surgical treatment for patients with diabetic foot ulcers in a semi-crossover designed RCT. Methods One hundred patients with diabetic neuropathy related foot ulcers (tip of toe ulcers, ulcers under metatarsal heads and ulcers under the hallux interphalangeal joint) will be randomized (2:3) to a surgical offloading procedure or best available non-surgical treatment. Group 1 (surgery) will have surgery within 1 week. Group 2 (controls) will be prescribed an offloading cast applied for up to 12 weeks (based on clinical considerations). Following successful offloading treatment (ulcer closure with complete epithelization) patients will be prescribed orthopaedic shoes and custom made orthotics. If offloading by cast for at least 6 weeks fails, or the ulcer recurs, patients will be offered surgical offloading. Follow-up will take place till 2 years following randomization. Outcome criteria will be time to healing of the primary ulcer (complete epithelization), time to healing of surgical wound, recurrence of ulcer, time to recurrence and complications. Discussion The high recurrence rate of foot ulcers and their dire consequences justify attempts to find better solutions than the non-surgical options available at present. To promote surgery, RCT level evidence of efficacy is necessary. Trial registration Israel MOH_2017–08-10_000719. NIH: NCT03414216

Effect of a tight glycemic control protocol on hypoglycemia and mortality in the burn unit: A case-control study

Background: Burn injury pathophysiology is characterized by severe catabolic state and poor glycemic control. A tight glycemic control protocol using insulin for burn victims has yielded inconsistent mortality and morbidity outcomes. Objectives: To compare the effect of standard and tight glycemic control protocols on mortality and hypoglycemia events in critical care burn patients. Methods: We conducted a case-control study of burn victims admitted to the burn intensive care unit between 2005 and 2011. Patients were assigned to either a standard or a tight glycemic control protocol. Results: Of the 38 burn patients in the study, 28 were under a tight glycemic control protocol. No differences in glucose area-under-the-curve per day levels were observed between the groups (148.3 ± 16 vs. 157.8 ± 16 mg/dl in the standard and tight glycemic control protocol groups respectively, P = 0.12). The hypoglycemic event rate was higher in the tight glycemic control protocol group (46.4% vs. 0%, P = 0.008). No difference in mortality rate was noted (67.9% vs. 50%, P = 0.31). Mortality independent risk factors found on multivariate analysis included total body surface area (adjusted hazard ratio [AHR] 1.039, 95% confidence interval [95%CI] 1.02–1.06, P = 0.001), white blood cell count on admission (AHR 1.048, 95%CI 1.01– 1.09, P = 0.02) and surgery during hospitalization (AHR 0.348, 95%CI 0.13–0.09, P = 0.03). Conclusions: The tight glycemic control protocol in burn patients was associated with higher rates of hypoglycemic events, and no association was found with improved survival in the acute setting of burn trauma care

Frequency of intra-abdominal organ injury is higher in patients with concomitant stab wounds to other anatomical areas

Abstract Background Management of stable patients with abdominal stab wound remains controversial, particularly for those with no clear indications for explorative laparotomy. We evaluated the risk of intra-abdominal injury in stab wound victims concomitantly stabbed in other anatomical body areas. Methods We performed a retrospective cohort study of patients with abdominal stab wounds recorded in the Israeli National Trauma Registry from January 1st, 1997, to December 31st, 2013. Patients with an isolated abdominal stab wound were compared to those with concomitant stab wounds to other anatomical areas. Intra-abdominal organ injury was defined by imaging or surgery findings. Multivariate analysis using a logistic regression model was conducted to assess independent risk for intra-abdominal organ injury. Results The study included 3964 patients. After controlling for age, gender and hypotension on arrival, patients with multi-regional stab wounds had an increased risk of intra-abdominal injury (OR = 1.3, CI 95% 1.1–1.6, p < 0.001). These patients also had a higher rate of injury to the solid organs than patients with an isolated abdominal stab wound. Conclusions Patients with multi-regional stab wounds have an increased risk of intra-abdominal injury. Worldwide accepted “clinical follow up” protocol may not be appropriate in management of patients with multi-regional stab wounds

Validation of the Hebrew version of the Burn Specific Health scale-brief questionnaire

Background The Burns Specific Health Scale-Brief (BSHS-B) questionnaire is a suitable measurement tool for the assessment of general, physical, mental, and social health aspects of the burn survivor. Aim To translate, culturally adapt and validate the BSHS-B to Hebrew (BSHS-H), and to investigate its psychometric properties. Methods Eighty-six Hebrew speaking burn survivors filled out the BSHS-B and SF-36 questionnaires. Ten of them (11.63%) completed a retest. The psychometric properties of the scale were evaluated. Internal consistency, criterion validity, and construct validity were assessed using interclass correlation coefficient, Cronbach's alpha statistic, Spearman rank test, and Mann–Whitney U test respectively. Results BSHS-H Cronbach's alpha coefficient was 0.97. Test–retest interclass coefficients were between 0.81 and 0.98. BSHS-H was able to discriminate between facial burns, hand burns and burns >10% body surface area (p < 0.05). BSHS-H and SF-36 were positively correlated (r2 = 0.667, p < 0.01). Conclusions BSHS-H is a reliable and valid instrument for use in the Israeli burn survivor population. The translation and cross-cultural adaptation of this disease specific scale allows future comparative international studies

The association between neck adiposity and long-term outcome.

Anthropometric indices of obesity (e.g. body mass index, waist circumference and neck circumference) are associated with poor long-term cardiovascular outcome. Prior studies have associated neck circumference and central body adiposity. We explored the association between neck fat volume (NFV) and long-term cardiovascular outcome. The study provides a retrospective analysis of all patients undergoing computerized tomography angiography for suspected cerebrovascular accident between January and December 2013. NFV was assessed by three dimensional reconstructions and was adjusted to height to account for differences in body sizes, thus yielding the NFV/height ratio (NHR). Univariate and multivariate analysis were utilized to explore the association between various indices including NHR and all-cause mortality. The analysis included 302 patients. The average age was 61.9±14.3 years, 60.6% of male gender. Diabetes mellitus, hypertension and cardiovascular disease were frequent in 31.5%, 69.9%, and 72.2% of patients, respectively. The median NHR was 492.53cm2 [IQR 393.93-607.82]. Median follow up time was 41.2 months, during which 40 patients (13.2%) died. Multivariate analysis adjusting for age, sex, and diabetes mellitus indicated an independent association between the upper quartile of NHR and all-cause mortality (hazard ratio = 2.279; 95% CI = 1.209-4.299; p = .011). NHR is a readily available anthropometric index which significantly correlated with poor long-term outcome. Following validation in larger scale studies, this index may serve a risk stratifying tool for cardiovascular disease and future outcome