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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.

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.

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 .

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.

Background: Phenol chemical peeling (PCP) treatment is associated with prolonged recovery and sustained adverse events. Hyperbaric oxygen therapy (HBOT) is known to accelerate wound healing. The purpose of the current study was to evaluate the effect of HBOT on PCP recovery period and adverse events. Methods: This is a pilot randomized controlled clinical study. Women following PCP underwent 5 consecutive daily HBOT sessions, compared with PCP alone. Pain, pruritus, erythema, crusting, scaling, and edema were daily evaluated up to 28 days following PCP. Photographs taken on days 14 and 35 following PCP were assessed. Confidence to appear in public was assessed 14 days following PCP. Results: Eight participants equally assigned to HBOT and control groups. Lower severity scores for erythema, scaling, and pruritus were documented in the HBOT group (mean difference 1.19, P = .006; .84, P = .04; and 2.19, P = .001, respectively). Photographic assessment severity score was higher for skin tightness, edema, erythema, crusting, and scaling in the control group on day 14 post PCP (P < .05) and for erythema on day 35 post PCP (P < .05). Epithelialization percentage was higher in the HBOT group on day 14 post PCP compared with controls (98.5% ± 1% vs 94.2% ± 1%; P = .021). The HBOT group scored higher in confidence to appear in public (20.8 ± 1.7 vs 14.5 ± 1.3; P = .029). Conclusion: Hyperbaric oxygen therapy following PCP is associated with faster recovery as assessed by both patients and caregivers. So far, HBOT was mainly used in the treatment of problematic or chronic wounds. Our study suggests expanding the indications in which hyperbaric oxygen treatment is applicable and recommended.

Introduction: The purpose of this study was to evaluate the most commonly used preoperative assessment tools for patients undergoing surgical treatment for secondary upper extremity lymphedema. Methods: This was a prospective cohort study performed at a tertiary cancer center specializing in the treatment of secondary lymphedema. Lymphedema evaluation included limb volume measurements, bio-impedance, indocyanine green lymphography, lymphoscintigraphy, magnetic resonance angiography, lymphedema life impact scale (LLIS) and upper limb lymphedema 27 (ULL-27) questionnaires. Results: 118 patients were evaluated. Limb circumference underestimated lymphedema compared to limb volume. Bioimpedance (L-Dex) scores highly correlated with limb volume excess (r2 = 0.714, p < 0.001). L-Dex scores were highly sensitive and had a high positive predictive value for diagnosing lymphedema in patients with a volume excess of 10% or more. ICG was highly sensitive in identifying lymphedema. Lymphoscintigraphy had an overall low sensitivity and specificity for the diagnosis of lymphedema. MRA was highly sensitive in diagnosing lymphedema and adipose hypertrophy as well as useful in identifying axillary vein obstruction and occult metastasis. Patients with minimal limb volume difference still demonstrated significantly impaired quality of life. Conclusion: Preoperative assessment of lymphedema is complex and requires multimodal assessment. MRA, L-Dex, ICG, and PROMs are all valuable components of preoperative assessment.

BackgroundAugmentation mammoplasty is one of the most common esthetic procedures worldwide. A wide range of motivations leads women to undergo this procedure, among them socioeconomic status and age group. The aim of this study was to identify the motivation spectrum for augmentation mammoplasty through different age groups.MethodsWe conducted a cross-sectional prospective survey given to Israeli women seeking augmentation mammoplasty consults in a hospital and private clinic settings, using a 17-item Motivation for Augmentation questionnaire. Three motivation domains were examined: appearance, sexuality and social. Study participants were divided into three age groups: 18–29, 30–39 and over 40 years.ResultsA total of 101 women participated in the study. Motivations were rated similar among all age groups. Appearance and sexuality domains were rated significantly higher compared with the social domain throughout all age groups (3.28 ± 0.91 and 3.15 ± 1.03 vs. 1.88 ± 1.16, p < 0.001, respectively).ConclusionsMotivations in Israeli women seeking breast augmentation do not change with age. The desire to improve one’s appearance and sexuality is more prominent than improving social and work status.Level of Evidence IVThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The threat of using variola virus in a bioterrorist attack urged different countries to renew the production of traditional vaccines and develop new generations of smallpox vaccines. Manufacturers try to combine smallpox vaccine past experience with technological advances in vaccine development to achieve protection similar to that of the traditional vaccines with a higher level of safety and fewer contraindications. In light of the reported immunogenicity and reactogenicity of the stockpiled smallpox vaccines employed in the last immunization campaigns of “first responders”, we review recently accumulated data on the assessment of new smallpox vaccine candidates and discuss their role in possible vaccination policies.

Introduction: Mass-casualty triage is implemented when available resources are insufficient to meet the needs of all patients in a disaster situation. The basic principle is to do the maximum good for the most casualties with the least amount of resources. There are limited data to support the applicability of this principle in massive disasters such as the January 2010 earthquake in Haiti, in which the number of patients seeking medical attention overwhelmed the local resources. Objective: To analyze the application of a triage system developed for use in a mass-casualty setting with limited resources. The system was designed to admit only those patients who had medical conditions requiring urgent treatment that were within the capabilities of the hospital and had a good chance of survival after discharge. Priority was given to those whose treatment could be administered within a short hospital stay. Method: A retrospective, observational review of computerized registration forms of Haitian earthquake victims who sought medical care at a 72-bed field hospital within four to 14 days after the event. An analysis of the efficacy of the triage protocol that was used followed, using length of hospital stay to measure consumption of resources. Results: A total of 1,111 patients were triaged for treatment in the field hospital within 14 days of the earthquake. The median length of stay for all patients for whom data was available was 16 hours (mean = 29.7 hours). The majority of patients (n = 620, 65%) were discharged within 24 hours. Two hundred five patients underwent surgery and were discharged within a median of 39 hours (mean = 52.6 hours); of these, 124 (62%) were discharged within 48 hours. The total mortality of the treated patients was 1.5% (n = 17). Conclusions: Currently accepted triage principles for the most part are appropriate for efficiently providing medical care in a disaster area with extremely limited resources, but require extensive adaptation to local conditions.

Background. Mass vaccination is the principal preventive measure against a smallpox outbreak after an act of bioterrorism. Vaccination of subjects who received immunosuppressive therapies is problematic because of smallpox vaccine reactogenicity. Moreover, long-term immunity to vaccinia might be affected. Objective. The objective of the study was to examine the effect of cytotoxic chemotherapy on long-term immunity to vaccinia. Methods. In a case-control study, 67 patients with breast cancer who received cytotoxic chemotherapy and who were disease free for at least 1 year were matched with healthy controls according to age, sex, and the number of smallpox vaccinations received. Markers of immunity to smallpox were examined. Forty-one patients with breast cancer who did not receive chemotherapy were used to assess the affect of cancer and radiotherapy on immunity to smallpox. Results. Patients with breast cancer who received chemotherapy had lower levels of vaccinia total immunoglobulin G and immunoglobulin G1 (expressed as enzyme-linked immunosorbent assay units per milliliter), neutralizing antibodies, vaccinia:memory B cell ratio (expressed as a percentage), and interferon-g level (expressed as picograms per milliliter), compared with healthy control individuals. Conclusions. Immunity to smallpox is reduced after receipt of chemotherapy for breast cancer. This finding should be considered when planning smallpox vaccination campaigns. The effect of immunosuppressive treatments on persistence of immunity should be tested with respect to additional vaccines or natural infections.