Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies.

BACKGROUND: Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the best regimens of these antibiotics in the burn patient population. METHODS: We performed a systematic review of evidence available on MEDLINE (from its inception to 2023) of pharmacology studies that focused on the use of 13 broad-spectrum beta-lactams in burn patients. We extracted and synthetized data on drug regimens and their ability to attain adequate PK/PD targets. RESULTS: We selected 35 studies for analysis. Overall, studies showed that both high doses and the continuous infusion (CI) of broad-spectrum beta-lactams were needed to achieve internationally-recognized PK/PD targets, ideally with therapeutic drug monitoring guidance. The most extensive evidence concerned meropenem, but similar conclusions could be drawn about piperacillin-tazobactam, ceftazidime, cefepime, imipenem-clinastatin and aztreonam. Insufficient data were available about new beta-lactam-beta-lactamase inhibitor combinations, ceftaroline, ceftobiprole and cefiderocol. CONCLUSIONS: Both high doses and CI of broad-spectrum beta-lactams are needed when treating burn patients due to the peculiar changes in the PK/PD of antibiotics in this population. Further studies are needed, particularly about newer antibiotics.

The history of Lyme disease in Italy and its spread in the Italian territory.

Lyme borreliosis (LB) is the most common vector-borne zoonotic inflammatory disease in the Northern Hemisphere. In Italy, the first case was diagnosed in 1985 in a woman in Liguria, while the second, in 1986 in Friuli-Venezia Giulia, documenting the infection in northern Italy. Both diagnoses were confirmed by serological assessment by an indirect immunofluorescence (IFI) technique. Borrelia cultivation from both Ixodes ricinus ticks and human lesions in Trieste (Friuli-Venezia Giulia) identified Borrelia afzelii as the prevalent genospecies; nevertheless, Borrelia garinii, Borrelia burgdorferi (sensu stricto), and Borrelia valaisiana (VS116 Group) were also detected, although less frequently. LB was also documented in other Italian regions: in Tuscany (1991), Trentino-Alto Adige (1995-1996), Emilia-Romagna (1998), Abruzzo (1998), and more recently, Lombardy. Nevertheless, data on LB in other Italian regions, especially in southern Italy and islands, are poor. The aim of this study is to document the spread of LB in Italy through the collection of data from LB patients in eight Italian hospitals located in different Italian regions. Diagnostic criteria for LB diagnosis are as follows: i) the presence of erythema migrans (EM) or ii) a clinical picture suggestive of LB, confirmed by serological tests and/or PCR positivity for Borrelia detection. In addition, data also included the place of residence (town and region) and the place where patients became infected. During the observation period, 1,260 cases were gathered from the participating centers. Although different in extent from northern Italy to central/southern Italy, this study shows that LB is widespread throughout Italy.

Eccrine Angiomatous Hamartoma with Atypical Localization Treated by Mohs Micrographic Surgery.

ABSTRACT: Eccrine angiomatous hamartoma (EAH) is a rare hamartoma characterized by a benign proliferation of eccrine glands and vascular structures in the dermis. These tumors rarely regress spontaneously, so surgical excision of the involved tissue is required when pain or enlargement occurs. Here, the authors report the clinical case of a patient affected by an extremely painful EAH with the atypical localization at the last phalanx of the thumb of the right hand with involvement of nail matrix and nail bed. This report aims to emphasize the application of Mohs micrographic surgery for the treatment of painful EAH in a very difficult area at potential risk of amputation while preserving the maximum anatomical integrity and function of the damaged area. These results can pave the way for the use of Mohs micrographic surgery for very carefully selected benign neoplasms when their surgical removal is required.

[Acute kidney injury in severely burned patient: prevention and treatment].

Acute Kidney Injury (AKI) is associated with a great increase in morbidity and mortality in severely burned patients and occurs as a complication in more than 25% of these cases. The onset of ARF may be early or late. Early AKI depends mainly on reduced cardiac output resulting from fluid loss, rhabdomyolysis, or hemolysis. Late AKI, instead, is usually a consequence of sepsis and is often associated with multiorgan failure (MOF). The first sign of AKI is the contraction of diuresis despite adequate volemic filling, which is followed by elevation of serum urea and creatinine. Fluid therapy is the main treatment in the burned victim: in the first few hours after injury, it aims to avoid hypovolemic shock and the possible related MOF, while later it becomes the cornerstone of treatment, besides antibiotic therapy in the case of sepsis onset. Particular care must also be taken in the choice of administered drugs in order to avoid possible nephrotoxic damage in addition to burning injury. Hemodialytic renal replacement therapy is used both for water balance management in patients requiring massive fluid infusions and for blood purification purposes to control the metabolic state, acid-base balance, and electrolytes abnormality. Our team has been collaborating for over 25 years in the management of severely burned patients admitted to the Centro Grandi Ustionati at the Bufalini Hospital in Cesena.

Subungual Metastasis from Ovarian Cancer: Case Report and Brief Review of the Literature.

Introduction: Visceral solid cancers can metastasize in almost any organ, including the skin and its appendages. Case Presentation: We report here the case of a 19-year-old Caucasian girl carrying a diagnosis of malignant germ cell tumor of the ovary, with pulmonary and brain metastases, that developed a painful red-violaceous subungual papule of the 4th finger of the left hand, associated with an over-curvature of the nail plate. Dermoscopy was characterized initially by different shades of pink and red, while after few weeks, it showed black pigmentation due to subcorneal hematomas, hemorrhagic crusts, and a rainbow pattern. Histology confirmed a diagnosis of a metastasis from a poorly differentiated carcinoma of ovarian origin. Discussion and Conclusion: A brief review on the diagnosis and treatment of subungual metastases is reported.

Chemical composition, antioxidant and anti-inflammatory properties of Monarda didyma L. essential oil.

In the present study, Monarda didyma L. essential oil (isolated from the flowering aerial parts of the plant) was examined to characterize its chemotype and to evaluate, in addition to the quali-quantitative chemical analysis, the associated antioxidant and anti-inflammatory activities. The plants were grown in central Italy, Urbino (PU), Marche region. Different analyses (TLC, GC-FID, GC-MS and 1H-NMR) allowed the identification of twenty compounds among which carvacrol, p-cymene and thymol were the most abundant. On this basis, the chemotype examined in the present study was indicated as Monarda didyma ct. carvacrol. The antioxidant effect was assessed by DPPH assay. Moreover, this chemotype was investigated for the anti-inflammatory effect in an in vitro setting (i.e., LPS-stimulated U937 cells). The decreased expression of pro-inflammatory cytokine IL-6 and the increased expression of miR-146a are suggestive of the involvement of the Toll-like receptor-4 signaling pathway. Although further studies are needed to better investigate the action mechanism/s underlying the results observed in the experimental setting, our findings show that M. didyma essential oil is rich in bioactive compounds (mainly aromatic monoterpenes and phenolic monoterpenes) which are most likely responsible for its beneficial effect.

Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.

Neonatal encephalopathy (NE) is a pathological condition affecting long-term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic-ischemic (HI) brain injury. However, unlike animal models that enable the study of the brain and the pathophysiologic cascade, only blood is available from human subjects. Therefore, due to the unavailability of neonatal brain tissue, assumptions about the pathophysiology in pathways and cascades are made in human subjects with NE. We analyzed animal and human specimens to improve our understanding of the pathophysiology in human neonates. A neonate with NE who underwent hypothermia and enrolled in a melatonin pharmacokinetic study was compared to HI rats treated/untreated with melatonin. MicroRNA (miRNA) analyses provided profiles of the neonate's plasma, rat plasma, and rat brain cortexes. We compared these profiles through a bioinformatics tool, identifying Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways common to HI brain injury and melatonin treatment. After evaluating the resulting pathways and the literature, to validate the method, the key proteins expressed in HI brain injury were investigated using cerebral cortexes. The upregulated miRNAs in human neonate and rat plasma helped identify two KEGG pathways, glioma and long-term potentiation, common to HI injury and melatonin treatment. A unified neonatal cerebral melatonin-sensitive HI pathway was designed and validated by assessing the expression of protein kinase Cα (PKCα), phospho (p)-Akt, and p-ERK proteins in rat brain cortexes. PKCα increased in HI-injured rats and further increased with melatonin. p-Akt and p-ERK returned phosphorylated to their basal level with melatonin treatment after HI injury. The bioinformatics analyses validated by key protein expression identified pathways common to HI brain injury and melatonin treatment. This approach helped complete pathways in neonates with NE by integrating information from animal models of HI brain injury.

The Use of Quercetin to Improve the Antioxidant and Regenerative Properties of Frozen or Cryopreserved Human Amniotic Membrane.

The biological properties of the human amniotic membrane (HAM) and its characteristic ability to be a reservoir of growth factors promoting wound healing make it an ideal biological dressing for the treatment of different clinical conditions, such as burns and non-healing wounds. However, the application of a preservation method on the HAM is required during banking to maintain biological tissue properties and to ensure the release overtime of protein content for its final clinical effectiveness after application on the wound bed. Although cryopreservation and freezing are methods widely used to maintain tissue properties, reactive oxygen species (ROS) are produced within tissue cellular components during their switching from frozen to thawed state. Consequently, these methods can lead to oxidative stress-induced cell injury, affecting tissue regenerative properties and its final clinical effectiveness. Taking advantage of the antioxidant activity of the natural compound quercetin, we used it to improve the antioxidant and regenerative properties of frozen or cryopreserved HAM tissues. In particular, we evaluated the oxidative damage (lipid peroxidation, malondialdehyde) as well as the regenerative/biological properties (bFGF growth factor release, wound healing closure, structure, and viability) of HAM tissue after its application. We identified the effectiveness of quercetin on both preservation methods to reduce oxidative damage, as well as its ability to enhance regenerative properties, while maintaining the unaltered structure and viability of HAM tissue. The use of quercetin described in this study appears able to counteract the side effects of cryopreservation and freezing methods related to oxidative stress, enhancing the regenerative properties of HAM. However, further investigations will need to be performed, starting from these promising results, to identify its beneficial effect when applied on burns or non-healing wounds.

Economic Burden of Denatured Alcohol-Induced Burns: A 20-Year Retrospective Study.

Burn care has rapidly improved over the past decades, but health innovations are expensive. We present the first study focusing on the economic burden of exclusive denatured alcohol-induced burns. The goal of this study was to determine costs for the public health system due to inpatients' burn care because of these specific burns. Moreover, we aimed to observe the incidence of methylated spirit-related burns in the past 20 years. We performed an observational retrospective study in our burn unit including all patients with a denatured alcohol-related burn injury from 1 January 2001 to 31 December 2020. A total of 503 patients with a mean burn size of 24% were hospitalized; the mean annual total costs per patient was €43,879, varying from €31,518 to €63,274.00€; the total costs for denatured alcohol-related burns during the period 2001-2020 was €21,145,076. We noted an increasing incidence of denatured alcohol-related burns and related costs over the years, especially in the last decade. Our results highlight that burns by methylated spirits are still a real and expanding problem. Therefore, authorities should focus on sales rules, characteristics of the containers, and education of people who misuse denatured alcohol, based on historical habits of use. To reduce the socioeconomic costs of burns, future intervention strategies and studies from the dermatology community and burn specialists should focus on prevention programs and prompt wound healing to shorten the length of hospital stay, enable quick return to work, and improve the outcomes of patients with burns.

Sub-muscular Reconstruction after NAC Sparing Mastectomy: Direct to Implant Breast Reconstruction with Human ADM Versus Tissue Expander.

BACKGROUND: Nipple areola complex (NAC) sparing mastectomy allows good oncological and aesthetic results. The study compares the results, in terms of self-evaluated satisfaction and symmetry, of direct to implant (DTI) sub-muscular breast reconstruction, with the aid of human acellular dermal matrix (ADM) versus two-stage reconstruction with sub-muscular tissue expander, followed by implant. MATERIALS AND METHODS: This is a retrospective, observational, single-center, non-randomized, case-control study. Inclusion criteria were: unilateral NAC sparing mastectomy at Forlì Hospital between 2014 and 2018; sub-muscular reconstruction; minimum follow-up of 12 months from the reconstructive stage; no history of radiotherapy. Patients were divided into two groups: group A included patients who underwent DTI breast reconstruction with the aid of human ADM; group B were those who underwent a two-stage reconstruction with tissue expander then implant. We collected data on: (1) Self-evaluated satisfaction by Breast Q questionnaire (scores from 0 to 100). (2) Observer-evaluated symmetry. Bi-dimensional photographs were collected and evaluated by 11 breast surgeons blinded to each other, who assigned a score for symmetry (from 0 to 10). (3) Symmetry of anthropometric measures collected by hand and volume estimated by Breast V application. RESULTS: Group A included 28 patients; group included B 26 patients. Breast-Q questionnaires reported the following results: satisfaction with breasts in group A 65 ± 12 versus group B 68 ± 14; satisfaction with outcome in group A 88 ± 16 versus group B 93 ± 11; psychosocial well-being in group A 71 ± 20 versus group B 76 ± 17; sexual well-being in group A 63 ± 26 versus group B 60 ± 13; physical well-being in group A 68 ± 15 versus group B 60 ± 12. The average symmetry breast score assigned to group A was 6.9, versus group B 7.2. Regarding the anthropometric measures in group A, the differences between right and left were major to those in group B. Regarding breast volume, the mean difference between right and left in group A was 31.89 cc ± 24.97, whereas in group B was 25.46 cc ± 23.59. CONCLUSION: Our data show better symmetry and better psychosocial well-being in the two-stage reconstruction, and higher satisfaction with sexual and physical well-being in DTI reconstructions. These aspects should be discussed with the patient while collecting the informed consent. LEVEL OF EVIDENCE IV: This 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 .

Italian recommendations on enzymatic debridement in burn surgery.

INTRODUCTION: Nexobrid®, a bromelain-based type of enzymatic debridement, has become more prevalent in recent years. We present the recommendations on enzymatic debridement (Nexobrid®)'s role based on the practice knowledge of expert Italian users. METHODS: The Italian recommendations, endorsed by SIUST (Italian Society of Burn Surgery), on using enzymatic debridement to remove eschars for burn treatment were defined. The definition followed a process to evaluate the level of agreement (a measure of consensus) among selected experts, representing Italian burn centers, concerning defined clinical aspects of enzymatic debridement. The consensus involved a multi-phase process based on the Delphi method. RESULTS: The consensus panel included experts from Italy with a combined experience of 1068 burn patients treated with enzymatic debridement. At the end of round 3 of the Delphi method, the panel reached 100% consensus on 26 out of 27 statements. The panel achieved full, strong consensus (all respondents strongly agreed on the statement) on 24 out of 27 statements. DISCUSSION: The statements provided by the Italian consensus panel represent a "ready to use" set of recommendations for enzymatic debridement in burn surgery that both draw from and complete the existing scientific literature on the topic. These recommendations are specific to the Italian experience and are neither static nor definitive. As such, they will be updated periodically as further quality evidence becomes available.

The Use of Allograft Skin for the Treatment of Darier Disease.

Darier disease is an autosomal dominant skin disorder characterized by keratotic papules. After their appearance, these lesions tend to grow over time, producing large and exudative plaques that compromise the general condition of the affected patient's skin. The authors report the clinical case of a patient affected by Darier disease with superinfected de-epithelialized areas over 30% of his body. In addition to antibiotic and antifungal therapy, providers used allograft skin to cover the injured areas and stimulate their progressive re-epithelialization with complete healing after 2 months. To the authors' knowledge, this is the first clinical case of treating Darier disease with allograft skin on an extensively damaged area. The effectiveness of this treatment may lead clinicians to consider allograft skin tissue a new, alternative dressing to treat Darier disease when this pathologic condition manifests with extensive eroded skin.

The Enzymatic Debridement for the Treatment of Burns of Indeterminate Depth.

The rapid eschar removal by surgical debridement is currently considered the standard of care for the treatment of burned patients. However, the excision of viable dermal residues can frequently occur when this procedure is applied affecting, in turn, the possible spontaneous re-epithelialization of the lesion area and increasing the amount of autologous skin grafts required for its treatment. To overcome these problems, the use of enzymatic debridement by proteolytic enzymes enriched in Bromelain has aroused great interest in the clinical field as a valid alternative to surgical procedure for the treatment of burns when they appear of indeterminate depth. With the aim to evaluate the effectiveness of this new approach in comparison with a surgical procedure for the treatment of these types of burns we performed a retrospective data analysis taking into account patients hospitalized in our Burn Center from 2014 to 2017. The results obtained show a significant reduction in the time frame to perform debridement when an enzymatic approach is chosen, with the maintenance of viable dermal tissue on the superficial areas of the wounds, their spontaneous re-epithelialization, and a reduction of the bleeding time in the treated patients. A reduced amount of autologous skin grafts is also used when enzymatic treatment is applied. The length of stay of the patients treated with enzymatic debridement did not show significant differences compared to that treated with surgery, with excellent aesthetic results after 1 to 3 years.

Efficacy of combined liman peloid baths and heliotherapy in the treatment of psoriasis at Cervia spa, Emilia, Italy.

This study assessed the effects of liman peloid, followed by bath and heliotherapy in psoriatic patients at Cervia, Emilia, Italy. The psoriatic patients were randomized into two groups: group 1 with 56 patients, treated with liman applications, bath, and heliotherapy, and group 2 with 35 subjects, treated with mud-bath therapy using a clay peloid mixed with tap water and heliotherapy. Data was collected for the following: psoriasis area and severity index (PASI); delta-PASI (difference between post- and pre-treatment PASI); delta-PASI3 and delta-PASI6, 3 and 6 months after the end of treatment, respectively; psoriasis recurrences; and the use of both topical and systemic drugs. Although not significant, a decrease in PASI was recorded in group 1 at the end of treatment and after 3 and 6 months. Compared with group 2, there was a significant change in delta-PASI, delta-PASI3, and psoriasis recurrences in group 1 as well as a significant reduction in the topical use of drugs, both cortisone and nonsteroid drugs. This is the first and preliminary study which documented the efficacy of a specific protocol of liman bath heliotherapy in psoriatic patients as documented by a reduction in delta-PASI and delta-PASI3, a decrease in psoriasis recurrences, and use of topical drugs.

A New Human-Derived Acellular Dermal Matrix for 1-Stage Coverage of Exposed Tendons in the Foot.

The closure of wounds associated with soft tissue defects is surgically challenging, frequently requiring extensive plastic surgery and free flaps. The combination of ADM and STSG is an innovative method used to cover such wounds. The human-derived ADMs (H-ADMs) are the most described in the literature but according to European legislations, Companies H-ADMs outside the EC are not allowed to commercialize them in Europe, H-ADMs being "human products" and not "medical devices", so being ruled by European legislations on transplants. The Skin Bank of the Bufalini Hospital (Cesena, Italy) obtained in 2009 the approval for the production and distribution of the first human cadaver-donor derived ADM from the Italian National Transplant Center and National Health Institute, we called with the Italian acronym M.O.D.A. (Matrice Omologa Dermica Acellulata). We present here the first use of a new H-ADM for treatment of distal lower extremity wounds with exposed tendons managed in one-stage pocedure with STSG. The excellent performance suggests that in cases where autologous tissue is unavailable or undesirable, the use of M.O.D.A. in one-stage procedure represents a promising alternative for covering wounds associated with tendons exposition.

When basal cell carcinomas became giant: an Italian multicenter study.

BACKGROUND: Giant basal cell carcinoma (GBCC) is a basal cell carcinoma (BCC) enlarged in a diameter more than 5 cm. Since GBCCs are a highly infrequent entity and the occurrence rate is approximately 0.5-1% out of all BCC types, only anecdotal cases are reported, and causes and characteristics inducing development of this tumor are not defined. OBJECTIVES: Evaluate causative factors and clinico-histological characteristics of GBCCs. METHODS: The study is a 6-month, hospital-based case series study performed in 12 Italian dermatologic centers. RESULTS: A total of 59 cases and 458 control BCCs were collected. No significant differences existed between the two groups if we take into account social or cultural factors. The average duration of GBCCs is considerably longer than controls. GBCCs are located on unexposed areas while BCCs are on areas not usually covered by clothes. Superficial histological subtype was more frequent in the BCCs group, while infiltrative in GBCCs. GBCCs showed significantly higher local invasiveness, and greater metastatic capacity. More than half of GBCCs had been previously treated with one or more treatments. CONCLUSIONS: Patients with GBCCs appear to belong to two categories: (i) those who present with GBCC due to delay in accessing medical attention, and (ii) those who have BCCs previously treated with inappropriate strategies. Only very few cases can be carried out with intrinsic biological features of tumor aggressiveness. Social and cultural conditions do not appear to be involved in the development of GBCCS. These observations may help clinicians in selecting correct therapeutic strategies in the treatment of BCCs, which give rise to GBCC.