INVESTIGATING THE RELATIONSHIP BETWEEN BLEEDING, CLOTTING, AND COAGULOPATHY DURING AUTOMATED PARTIAL REBOA STRATEGIES IN A HIGHLY LETHAL PORCINE HEMORRHAGE MODEL.

ABSTRACT: Background: Death due to hemorrhagic shock, particularly, noncompressible truncal hemorrhage, remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently, whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer. In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared with pREBOA due to more oscillatory flow. Methods: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 min of automated pREBOA, iREBOA, or no balloon support (control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., eight key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 min). Citrated kaolin heparinase assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between the iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R time: P < 0.001; K time: P < 0.001) and clot strength (MA: P = 0.01; G: P = 0.02) over the duration of the experiment. Conclusions: Despite observing acute differences in peak proximal pressures between the iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.

A Comparative Analysis of "Surgery First" vs. "Endoscopy First" for Pediatric Choledocholithiasis Presenting at the End of the Week.

BACKGROUND: Choledocholithiasis in children is commonly managed with an "endoscopy first" (EF) strategy (endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) under a separate anesthetic). Endoscopic Retrograde Cholangiopancreatography is limited at the end of the week (EoW). We hypothesize that a "surgery first" (SF) approach with LC, intraoperative cholangiogram (IOC), and possible laparoscopic common bile duct exploration (LCBDE) can decrease length of stay (LOS) and time to definitive intervention (TTDI). METHODS: This is a retrospective single-center cohort study conducted between 2018 and 2023 in pediatric patients with suspected choledocholithiasis. Work week (WW) presentation included admission between Monday and Thursday. Time to definitive intervention was defined as time to LC. RESULTS: 88 pediatric patients were identified, 61 managed with SF (33 WW and 28 EoW) and 27 managed with EF (18 WW and 9 EoW). Both SF groups had shorter mean LOS for WW and EoW presentation (64.5 h, 92.4 h, 112.9 h, and 113.0 h; P < .05). There was a downtreading TTDI in the SF groups (SF: WW 24.7 h and EoW 21.7 h; EF: WW 31.7 h and EoW 35.9 h; P = .11). 44 patients underwent LCBDE with similar success rates (91.6% WW and 85% EoW; P = 1.0). All EF patients received 2 procedures; 69% of SF patients were definitively managed with one. CONCLUSION: Children with choledocholithiasis at the EoW have a longer LOS and TTDI. These findings are amplified when children enter an EF treatment pathway. An SF approach results in shorter LOS with fewer procedures, regardless of the time of presentation.

MAN VERSUS MACHINE: PROVIDER DIRECTED VERSUS PRECISION AUTOMATED CRITICAL CARE MANAGEMENT IN A PORCINE MODEL OF DISTRIBUTIVE SHOCK.

ABSTRACT: Background: Critical care management of shock is a labor-intensive process. Precision Automated Critical Care Management (PACC-MAN) is an automated closed-loop system incorporating physiologic and hemodynamic inputs to deliver interventions while avoiding excessive fluid or vasopressor administration. To understand PACC-MAN efficacy, we compared PACC-MAN to provider-directed management (PDM). We hypothesized that PACC-MAN would achieve equivalent resuscitation outcomes to PDM while maintaining normotension with lower fluid and vasopressor requirements. Methods : Twelve swine underwent 30% controlled hemorrhage over 30 min, followed by 45 min of aortic occlusion to generate a vasoplegic shock state, transfusion to euvolemia, and randomization to PACC-MAN or PDM for 4.25 h. Primary outcomes were total crystalloid volume, vasopressor administration, total time spent at hypotension (mean arterial blood pressure <60 mm Hg), and total number of interventions. Results : Weight-based fluid volumes were similar between PACC-MAN and PDM; median and IQR are reported (73.1 mL/kg [59.0-78.7] vs. 87.1 mL/kg [79.4-91.8], P = 0.07). There was no statistical difference in cumulative norepinephrine (PACC-MAN: 33.4 µg/kg [27.1-44.6] vs. PDM: 7.5 [3.3-24.2] µg/kg, P = 0.09). The median percentage of time spent at hypotension was equivalent (PACC-MAN: 6.2% [3.6-7.4] and PDM: 3.1% [1.3-6.6], P = 0.23). Urine outputs were similar between PACC-MAN and PDM (14.0 mL/kg vs. 21.5 mL/kg, P = 0.13). Conclusion : Automated resuscitation achieves equivalent resuscitation outcomes to direct human intervention in this shock model. This study provides the first translational experience with the PACC-MAN system versus PDM.

Contemporary outcomes for arterial reconstruction with non-saphenous vein cryo-preserved conduits.

OBJECTIVE: Cryopreserved (CP) products are utilized during challenging cases when autogenous or prosthetic conduit use is not feasible. Despite decades of experience with cadaveric greater saphenous vein (GSV), there is limited available data regarding the outcomes and patency of other CP products, specifically arterial and deep venous grafts. This study was designed to evaluate outcomes of non-GSV CP conduits in patients undergoing urgent, emergent, and elective arterial reconstruction at our institution. We hypothesized that non-GSV CP allografts have adequate patency and outcomes and are therefore a feasible alternative to GSV in settings where autologous graft is unavailable or prosthetic grafts are contraindicated. METHODS: This study was approved by the Institutional Review Board at our institution. We retrospectively reviewed charts of patients undergoing arterial reconstructions using CP conduits from 2010 to 2022. Data collected included demographics, comorbidities, smoking status, indications for surgery, indication for CP conduit use, anatomic reconstruction, urgency of procedure, and blood loss. Time-to-event outcomes included primary and secondary graft patency rates, follow-up amputations, and mortality; other complications included follow-up infection/reinfection and 30-day complications, including return to the operating room and perioperative mortality. Time-to-event analyses were evaluated using product-limit survival estimates. RESULTS: Of 96 identified patients receiving CP conduits, 56 patients received non-GSV conduits for 66 arterial reconstructions. The most common type of non-GSV CP product used was femoral artery (31 patients), followed by aorto-iliac artery (22 patients), and femoral vein (19 patients), with some patients receiving more than one reconstruction or CP product. Patients were mostly male (75%), with a mean age of 63.1 years and a mean body mass index of 26.7 kg/m2. Indications for CP conduit use included infection in 53 patients, hostile environment in 36 patients, contaminated field in 30 patients, tissue coverage concerns in 30 patients, inadequate conduit in nine patients, and patient preference in one patient. Notably, multiple patients had more than one indication. Most surgeries (95%) were performed in urgent or emergent settings. Supra-inguinal reconstructions were most common (53%), followed by extra-anatomic bypasses (47%). Thirty-day mortality occurred in 10 patients (19%). Fifteen patients (27%) required return to the operating room for indications related to the vascular reconstructions, with 10 (18%) cases being unplanned and five (9%) cases planned/staged. Overall survival at 6, 12, and 24 months was 80%, 68%, and 59%, respectively. Primary patency at 6, 12, and 24 months was 86%, 70%, and 62%, respectively. Amputation freedom at 6 months, 12 months, and 24 months was 98%, 95%, and 86%, respectively for non-traumatic indications. CONCLUSIONS: Non-GSV CP products may be used in complex arterial reconstructions when autogenous or prosthetic options are not feasible or available.

Spare the Needle, Discharge the Child: Trending Post-Op Labs After Laparoscopic Common Bile Duct Exploration in Pediatric Patients Is Not Helpful.

Laparoscopic common bile duct exploration (LCBDE) utility in management of choledocholithiasis may decrease length of stay and patient cost, but postoperative management remains widely debated. We examined periprocedural LFTs for patients undergoing LCBDE and endoscopic retrograde cholangiopancreatography (ERCP) speculating for trend existence after successful LCBDE. We hypothesized that postoperative LCBDE LFTs would not downtrend even after successful ductal clearance. We identified 99 patients under 18 who underwent ERCP or LCBDE with at least one pre- and post-procedural LFT. Periprocedural LFTs between groups were compared using Wilcoxon signed-rank tests. The 22 ERCP patients demonstrated a significant downtrend across Tbili (P < .001), AST (P = .001), ALT (P = .002), and ALP (P < .001). The 27 LCBDE patients demonstrated a significant downtrend in Tbili (P = .002) only, while AST (P > .05), ALT (P > .05), and ALP (P > .05) were nonsignificant. Lack of consistent downtrend in the LCBDE group raises doubt regarding the utility of postoperative LFTs for post-procedural management.

Transcystic Laparoscopic Common Bile Duct Exploration for Pediatric Patients with Choledocholithiasis: A Multi-Center Study.

BACKGROUND: Patients with choledocholithiasis are often treated with endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Upfront LC, intraoperative cholangiogram (IOC), and possible transcystic laparoscopic common bile duct exploration (LCBDE) could potentially avoid the need for ERCP. We hypothesized that upfront LC + IOC ± LCBDE will decrease length of stay (LOS) and the total number of interventions for children with suspected choledocholithiasis. METHODS: A multicenter, retrospective cohort study was performed on pediatric patients (<18 years) between 2018 and 2022 with suspected choledocholithiasis. Demographic and clinical data were compared for upfront LC + IOC ± LCBDE and possible postoperative ERCP (OR1st) versus preoperative ERCP prior to LC (OR2nd). Complications were defined as postoperative pancreatitis, recurrent choledocholithiasis, bleeding, or abscess. RESULTS: Across four centers, 252 children with suspected choledocholithiasis were treated with OR1st (n = 156) or OR2nd (n = 96). There were no differences in age, gender, or body mass index. Of the LCBDE patients (72/156), 86% had definitive intraoperative management with the remaining 14% requiring postoperative ERCP. Complications were fewer and LOS was shorter with OR1st (3/156 vs. 15/96; 2.39 vs 3.84 days, p < 0.05). CONCLUSION: Upfront LC + IOC ± LCBDE for children with choledocholithiasis is associated with fewer ERCPs, lower LOS, and decreased complications. Postoperative ERCP remains an essential adjunct for patients who fail LCBDE. Further educational efforts are needed to increase the skill level for IOC and LCBDE in pediatric patients with suspected choledocholithiasis. LEVEL OF EVIDENCE: Level III.

Automated partial resuscitative endovascular balloon occlusion of the aorta reduces blood loss and hypotension in a highly lethal porcine liver injury model.

BACKGROUND: Partial and intermittent resuscitative endovascular balloon occlusion of the aorta (pREBOA and iREBOA, respectively) are lifesaving techniques designed to extend therapeutic duration, mitigate ischemia, and bridge patients to definitive hemorrhage control. We hypothesized that automated pREBOA balloon titration compared with automated iREBOA would reduce blood loss and hypotensive episodes over a 90-minute intervention phase compared with iREBOA in an uncontrolled liver hemorrhage swine model. METHODS: Twenty-four pigs underwent an uncontrolled hemorrhage by liver transection and were randomized to automated pREBOA (n = 8), iREBOA (n = 8), or control (n = 8). Once hemorrhagic shock criteria were met, controls had the REBOA catheter removed and received transfusions only for hypotension. The REBOA groups received 90 minutes of either iREBOA or pREBOA therapy. Surgical hemostasis was obtained, hemorrhage volume was quantified, and animals were transfused to euvolemia and then underwent 1.5 hours of automated critical care. RESULTS: The control group had significantly higher mortality rate (5 of 8) compared with no deaths in both REBOA groups, demonstrating that the liver injury is highly lethal ( p = 0.03). During the intervention phase, animals in the iREBOA group spent a greater proportion of time in hypotension than the pREBOA group (20.7% [16.2-24.8%] vs. 0.76% [0.43-1.14%]; p < 0.001). The iREBOA group required significantly more transfusions than pREBOA (21.0 [20.0-24.9] mL/kg vs. 12.1 [9.5-13.9] mL/kg; p = 0.01). At surgical hemostasis, iREBOA had significantly higher hemorrhage volumes compared with pREBOA (39.2 [29.7-44.95] mL/kg vs. 24.7 [21.6-30.8] mL/kg; p = 0.04). CONCLUSION: Partial REBOA animals spent significantly less time at hypotension and had decreased transfusions and blood loss. Both pREBOA and iREBOA prevented immediate death compared with controls. Further refinement of automated pREBOA is necessary, and controller algorithms may serve as vital control inputs for automated transfusion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Simulation in Surgical Resident Education: A Porcine Hemostasis and Laparoscopic Model.

The steep learning curve associated with learning laparoscopic techniques and limited training opportunities represents a challenge to general surgery resident training. The objective of this study was to use a live porcine model to improve surgical training in laparoscopic technique and management of bleeding. Nineteen general surgery residents (ranging from PGY 3 to 5) completed the porcine simulation and completed pre-lab and post-lab questionnaires. The institution's industry partner served as sponsors and educators on hemostatic agents and energy devices. Residents had a significant increase in confidence with laparoscopic techniques and the management of hemostasis (P = .01 and P = .008, respectively). Residents agreed and then strongly agreed that a porcine model was suitable to simulate laparoscopic and hemostatic techniques, but there was no significant change between pre- and post-lab opinions. This study demonstrates that a porcine lab is an effective model for surgical resident education and increases resident confidence.

Resolution of Liver Function Tests After Laparoscopic Common Bile Duct Exploration Versus Endoscopic Retrograde Cholangiopancreatography.

Laparoscopic cholecystectomy (LC) with laparoscopic common bile duct exploration (LCBDE) is gaining traction for the management of choledocholithiasis. Liver function tests (LFTs) are often used to determine the success of ductal clearance, yet the impact of differing therapeutic interventions, endoscopic retrograde cholangiopancreatography (ERCP) or LCBDE, have on postprocedure LFT is insufficiently described. We hypothesize that these interventions have different postoperative LFT profiles. The preprocedural and postprocedural total bilirubin (Tbili), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were analyzed of 167 patients who had successful ERCPs (117) or LCBDEs (50). Endoscopic retrograde cholangiopancreatography patients demonstrated a significant decrease in all LFTs postprocedure (n = 117; P = <0.001 for all) with a continued downtrend when a second set of LFTs was obtained (n = 102; P = <0.001 for all). For successful LC+LCBDEs, there was no significant change between preoperative and 1st postoperative Tbili, AST, ALT, and ALP and the 2nd postoperative labs.

Primary cutaneous adenoid cystic carcinoma of the scalp: dermatosurgical approach with favourable outcome.

Although described as early as 1975 as a distinct, rare form of cancer with diverse localization, primary cutaneous adenoid cystic carcinoma (PCACC) remains a mystery and challenge for both clinicians and pathologists. The clinical presentation cannot be clearly distinguished from amelanotic melanoma or intradermal nevus, Merkel cell carcinoma, trichofolliculoma, trichoepithelioma or other rare tumors of the adnexa, or dermatofibrosarcoma protuberans. The histopathological diagnosis requires not only careful evaluation of standard hematoxylin/eosin preparations, but also immunohistochemical staining with a number of markers such as epithelial membrane antigen (EMA), S-100, SOX-10, Ki- 67, CD-117 (c-kit), Vimentin, carcinoembryonic antigen (CEA), Ber-EP4 and many others. The surgical approach should consist of excision with margins between 1 and 2 cm, with the choice of margins depending upon the histopathological findings in the primary excisional specimen. We present a 31-year-old patient with an enlarging, amelanotic, plaque-like tumor of the scalp with a duration of no more than 18-24 months. Surgical treatment was performed within two surgical sessions with a total resection field of 1.3 cm. A good cosmetic result was achieved.

Early trajectories of motor skills in infant siblings of children with autism spectrum disorder.

Delays in motor development are not considered a core feature of autism spectrum disorder (ASD). Yet, recent studies of infant siblings of children with ASD suggest that early delays in motor skills may be associated with later delays in developmental areas considered to be core features of an ASD diagnosis. While these studies demonstrate the longitudinal association between core features and motor delays observed at single time points, there is considerable interest in studying the trajectories of motor development over the first 3 years of life. To accomplish this, we investigated early trajectories of motor development in a cohort of 499 infant siblings of children with ASD and 176 children with no family history of ASD. Data for the current study were drawn from the prospective, multi-site, Canadian Infant Sibling Study. We evaluated trajectories of fine and gross motor development over the first 3 years using group-based trajectory modeling. Our results show that membership for both fine and gross motor trajectory groups was related to expressive language skills, receptive language skills, ASD symptom severity scores, and diagnostic classification at age 3. These results provide evidence that the trajectory of a child's early motor development may have important prognostic implications in ASD.

Telmisartan (and/or nitrosamine) - induced occult melanoma: first reported case in world literature.

Introduction: The known connections between the terms 'sartans' and 'melanoma' has grown recently in the clinical field, suggesting that the relationship between these concepts is very likely to be significant, rather than hypothetical or unfeasible. This is because: 1) the presence of angiotensin receptors in melanoma tissue, melanocytes and skin is a known fact; 2) the influence of sartans on the processes of melanogenesis has already been presented in recent published scientific papers; 3) key in vitro studies have shown that angiotensin receptor blockers (sartans) could potentiate carcinogenesis in the direction of melanoma and metastases; and 4) clinical examples of the occurrence of melanoma after starting therapy with sartans have become numerous and difficult to ignore.Areas covered: We report the first case of occult melanoma in an 87-year-old Bulgarian patient, this manifested in the form of a solitary metastasis on the left arm, which occurred after long-term therapy with telmisartan.Expert opinion: The fact that nitrosamines have a proven carcinogenic effect and are the cause of heterogeneous neoplasms shows that they have the potential to be possible melanoma triggers. The multifactorial pathogenesis of melanoma could certainly be clarified after the 'crystallization' of this currently serious issue.

Immunogenicity in humans of a transdermal multipeptide melanoma vaccine administered with or without a TLR7 agonist.

BACKGROUND: Experimental cancer vaccines are traditionally administered by injection in subcutaneous tissue or muscle, commonly with adjuvants that create chronic inflammatory depots. Injection of melanoma-derived peptides induces T cell responses; however, the depots that form following injection may inhibit optimization of the immune response. In skin, epidermal Langerhans cells (LC) are a dominant source of professional antigen presenting cells. We hypothesized that: (1) applying melanoma-derived peptides topically, in proximity to LC, could be immunogenic and safe, with low vaccine-site toxicity and (2) topical toll-like receptor 7 (TLR7) agonist would increase immunogenicity of the peptide vaccine. METHODS: Twelve melanoma peptides plus a tetanus helper peptide were combined with granulocyte macrophage colony stimulating factor (GM-CSF) and were administered topically on days 1, 8, and 15, to 28 patients randomized to one of four adjuvant preparations: (1) incomplete Freund's adjuvant (IFA); (2) IFA plus a TLR7 agonist (imiquimod) administered on days 0, 7, 14; (3) dimethyl sulfoxide (DMSO) or (4) DMSO+ imiquimod administered on day 0, 7, 14. Every 3 weeks thereafter (x 6), the peptides were combined with GM-CSF and were injected into the dermis and subcutis in an emulsion with IFA. Toxicities were recorded and immune responses assayed by ELIspot. RESULTS: CD8+ T cell responses to transdermal vaccination in DMSO occurred in 83% of participants in group 3 and 86% in group 4, and responses to vaccination in IFA were observed in 29% of participants in group 1 and 14% in group 2. Overall, 61% of participants had CD4+ T cell immune responses to the tetanus peptide, with large, durable responses in groups 3 and 4. Five of seven participants in group 4 had a severe rash, one that was dose limiting. Ten-year overall survival was 67% and disease-free survival was 44%. CONCLUSIONS: These data provide proof of principle for immunogenicity in humans of transdermal immunization using peptides in DMSO. Further study is warranted into the pharmacokinetics and immunobiology of TLR agonists as vaccine adjuvants during transcutaneous application. Overall survival is high, supporting further investigation of this immunization approach.

Telmisartan/hydrochlorothiazide-induced nevus-associated cutaneous melanoma: first report in the medical literature.

Introduction: The treatment of hypertension with certain groups of drugs may be problematic, particularly because certain drugs are capable of potentiating carcinogenesis. The presence of various receptors or components of the renin - angiotensin system in the skin, and particularly in melanocytes, determines the possible influence on this tissue by the so-called angiotensin receptor blockers or sartans. Thiazide diuretics can further influence the processes of carcinogenesis in all forms of skin cancer - melanocytic and non-melanocytic.Areas covered: We present a 67-year-old patient treated for a period of 3 years with a combined preparation containing Telmisartan/hydrochlorothiazide 80 mg/12.5 mg. Within 2 years, the patient observed the rapid development of a nevus that progressed to melanoma and was subsequently identified histopathologically as nevus-associated cutaneous melanoma with a 0.6 mm thickness, Clark IV. Following surgical treatment, no tumor progression has occurred to date. To our knowledge, this is the first reported case of a patient who developed a nevus-associated cutaneous melanoma after combination therapy with generic sartan and hydrochlorothiazide.Expert opinion: We discuss the diverse but mutually potentiating pro-carcinogenic effects of this class of agents, potentially leading to the development of cutaneous melanoma.

A novel surgical margin (1 cm) might be from benefit for patients with dysplastic nevi, thin melanomas, and melanoma in situ: Analysis based on clinical cases.

Malignant melanoma is an oncologic disease, whose current management among others includes surgical and immunological therapy. According to the current recommendations of the American Joint Committee on Cancer, the surgical excision of the primary tumor should be performed in two operative sessions, which has several consequences. The following paper will present and discuss six cases of pigmented lesions and the advantages of the one-step melanoma surgery in their management.

Granulomatous slack skin mycosis fungoides developing simultaneously with sarcoid-like lesions in a patient with repeated anabolic injections in the past?

We present a 32-year-old man with successful treatment and remission of mycosis fungoides of both axillae in 2016 after PUVA therapy and systemic and local administration of corticosteroids. Subsequently, in 2017, the patient also achieved remission of a T-cell CD 30 positive, ALK-1 negative large-cell lymphoma of a retroperitoneal and inguinal lymph node after chemotherapy and radiotherapy. One year later, in 2018, the patient presented to our clinic with progression of skin lesions in both axillary areas and the appearance of а tumor in the right gluteal region.Dermatological examination showed livid-to-erythematous, partly sclerotic plaques in the right inguinal area, cutis laxa-like plaque formations in the right axillary region with similar but less-developed changes in the left axillary fold, a solitary subcutaneous tumor formation affecting the entire right gluteal region, and enlarged, palpable lymph nodes in the right para-axillary area. Biopsies were obtained from an axillary lesion and the surgically removed axillary lymph nodes, and histological examination revealed changes of granulomatous slack skin in the axilla and reactive inflammatory changes in the lymph nodes. Histology of gluteal tissue showed a "foreign body" type of reaction with sarcoid-like features, where the patient in the past have been injected with anabolic and steroidal drugs. Herein we describe a patient with simultaneous occurrence of granulomatous slack skin type mycosis fungoides and a sarcoid-like reaction. The question remains open whether this represents the so-called sarcoidosis-lymphoma syndrome or, more likely, granulomatous slack skin MF associated with a sarcoid-like reaction of "foreign body" type. The possibility that disturbance of tissue homeostasis by incorporation of certain adjuvants within injections (for example) in the past might have been an inducer of cutaneous T cell lymphoma and sarcoidosis/sarcoid like lesions seems reasonable but also speculative.

Scleromyxedema (Arndt - Gottron Syndrome) Developing Under Tenofovir Treatment for Hepatitis B: Unique Presentation in a Bulgarian Patient!

BACKGROUND: Scleromyxedema, also referred to as the Arndt-Gottron (S-AG) syndrome or the systemic form of Lichen myxedematosus (LM), is a cutaneous mucinosis with a chronic course and high lethality from systemic involvement of other organs and systems. Interesting in several aspects is the association between scleromyxedema and viral hepatitis about: 1) hepatitis virus infection as a possible etiological factor for the development of scleromyxedema, 2) antiretroviral therapy for the treatment of hepatitis as a method of reversing scleromyxedema and 3) antiviral drugs as inducers of scleromyxedema. CASE REPORT: We present a 53-year old patient who for nine months had been on tenofovir disoproxil 245 mg (0-0-1) therapy for chronic hepatitis B. Three months after the start of antiviral therapy (i.e. for a period of 6 months), the patient observed swelling, itching and hardening of the skin on the face, ears and hands, which subsequently spread throughout the trunk. Subsequent histological study of a skin biopsy revealed changes of scleromyxedema at an advanced stage, though immunoelectrophoresis of serum and urine excluded the presence of paraproteinaemia or para proteinuria. Systemic antihistamine and topical corticosteroid therapy were instituted. Bone involvement with possible plasmacytoma was excluded, and a myelogram showed evidence of an erythroblastic reaction of bone marrow. CONCLUSION: We believe that drug-induced scleromyxedema is a rare but possible phenomenon. We describe the first case of tenofovir-induced scleromyxedema within the framework of chronic hepatitis B treatment.

Cutaneous paraneoplastic syndromes.

A variety of cutaneous abnormalities can be seen in patients with malignant diseases, some of which are infectious, with others representing direct involvement of the skin by the underlying disorder. Yet another group of lesions can be regarded as associated markers of the malignant process, and, as such, are termed "paraneoplastic." This review considers the latter collection of conditions, grouping them by the generic type of malignancy that is usually linked to the paraneoplasia. Some of the processes show a predominant association with alimentary tract malignancies (acanthosis nigricans, acrodermatitis paraneoplastica, florid cutaneous papillomatosis, necrolytic migratory erythema, palmoplantar keratoderma, pancreatic fat necrosis, and pityriasis rotunda). Others are usually linked to a hematolymphoid malignancy (acquired ichthyosis, exfoliative erythroderma, necrobiotic xanthogranuloma, pemphigus paraneoplastica, plane xanthoma, pyoderma gangrenosum, scleromyxedema, Sweet syndrome, and leukocytoclastic vasculitis). Finally, yet another collection of paraneoplastic skin disorders can associate themselves with anatomically-diverse malignancies (Leser-Trelat syndrome, Trousseau syndrome, dermatomyositis, erythema gyratum repens, hypertrichosis lanuginosa acquisita, papuloerythroderma of Ofuji, tripe palms, and multicentric reticulohistiocytosis). Recognition of these processes by the pathologist can be a valuable step in the characterization of underlying malignant diseases.

Diagnostic histochemistry in non-neoplastic skin diseases.

Non-neoplastic skin lesions comprise a sizable group of disorders with variable etiologies and clinical manifestations. They can be grouped into vesiculopustular dermatitides; spongiotic and psoriasiform diseases; lichenoid dermatitides; lymphoid infiltrates of the dermis; granulomatous processes; bullous disorders; vasculopathies; panniculitides; deposition disorders; and defects in maintenance of dermal connective tissue. The use of histochemical methods continues to be an indispensable adjunct to conventional microscopy in the further characterization of such lesions. This review considers that topic.