Botulinum Toxin-A Infiltration to Control Post-Operative Pain after Mastectomy and Expander Reconstruction as Potentially Useful Tool: A Narrative Review.

Botulinum toxin-A (BTX-A), a neurotoxin produced by Clostridium botulinum, was assessed for relieving implant-related pectoralis major muscle's painful spasms. In detail, 100 units of BTX-A can reduce muscle activity and, as a consequence, muscle spasms. The latter is considered the leading cause of post-operative pain after the sub-pectoral tissue expansion, sometimes leading to early expanders' removal. In addition, women choosing post-mastectomy reconstruction surgery seem to suffer worse post-operative pain than those who stop at the mastectomy stage. However, there is no unanimous consensus concerning the potential benefits of BTX-A in reducing pain related to the sub-pectoral placement of tissue expanders in breast reconstruction due to the exiguity of evidence. Therefore, this review aims to describe BTX-A-related evidence in this reconstruction setting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Is Quality of Life After Breast Reduction Influenced by Different Surgery's Technique? A Prospective Study.

BACKGROUND: Breast hyperplasia is a condition with a significant impact on the quality of life and psychological well-being of patients. Over time, various surgical techniques have been developed to reduce breast mass, which have proven effective in improving the quality of life of women undergoing the procedure. It is not yet well described how various techniques may influence the improvement in QoL (Quality of Life). The aim of this study is to assess the impact of different techniques on the improvement of quality of life. MATERIAL AND METHODS: We analyzed the responses to the Breast-Q questionnaire from 95 patients undergoing breast reduction surgery between 2021 and 2023. The questionnaires were completed both before the procedure and during the 6-month follow-up. We assessed the questionnaire responses and overall satisfaction with the results, categorizing the data based on the specific surgical technique used. RESULTS: A statistically significant improvement in the quality of life was observed in the postoperative period, as well as a remarkable satisfaction with the outcome (mean score of 81 out of 100). We did not detect statistically significant differences in the levels of quality of life and satisfaction with the outcome among the various techniques. CONCLUSION: The breast reduction surgery procedure continues to prove its ability to significantly improve the quality of life for patients with breast hypertrophy, regardless of the specific surgical technique employed. LEVEL OF EVIDENCE III: 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 .

Highly Concentrated Stabilized Hybrid Complexes of Hyaluronic Acid: Rheological and Biological Assessment of Compatibility with Adipose Tissue and Derived Stromal Cells towards Regenerative Medicine.

Cells and extracts derived from adipose tissue are gaining increasing attention not only in plastic surgery and for aesthetic purposes but also in regenerative medicine. The ability of hyaluronan (HA) to support human adipose stromal cell (hASC) viability and differentiation has been investigated. However, the compatibility of adipose tissue with HA-based formulation in terms of biophysical and rheological properties has not been fully addressed, although it is a key feature for tissue integration and in vivo performance. In this study, the biophysical and biochemical properties of highly concentrated (45 mg/mL) high/low-molecular-weight HA hybrid cooperative complex were assessed with a further focus on the potential application in adipose tissue augmentation/regeneration. Specifically, HA hybrid complex rheological behavior was observed in combination with different adipose tissue ratios, and hyaluronidase-catalyzed degradation was compared to that of a high-molecular-weight HA (HHA). Moreover, the HA hybrid complex's ability to induce in vitro hASCs differentiation towards adipose phenotype was evaluated in comparison to HHA, performing Oil Red O staining and analyzing gene/protein expression of PPAR-γ, adiponectin, and leptin. Both treatments supported hASCs differentiation, with the HA hybrid complex showing better results. These outcomes may open new frontiers in regenerative medicine, supporting the injection of highly concentrated hybrid formulations in fat compartments, eventually enhancing residing staminal cell differentiation and improving cell/growth factor persistence towards tissue regeneration districts.

Late relapse after CAR-T cell therapy for adult patients with hematologic malignancies: A definite evidence from systematic review and meta-analysis on individual data.

Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.

Current and future therapeutic perspective in chronic heart failure.

The incidence of heart failure is primarily flat or declining for a presumably reflecting better management of cardiovascular diseases, but that of heart failure with preserved ejection fraction (HFpEF) is probably increasing for the lack of an established effective treatment. Moreover, there is no specific pharmacological treatment for patients with heart failure with mildly reduced ejection fraction (HFmrEF) since no substantial prospective randomized clinical trial has been performed exclusively in such population. According to the recent 2021 European Society of Cardiology (ESC) guidelines, the triad composed of an Angiotensin Converting Enzyme inhibitor or Angiotensin Receptor-Neprilysin Inhibitor (ARNI), a beta-blocker, and a Mineralcorticoid Receptor Antagonist is the cornerstone therapy for all patients with heart failure with reduced ejection fraction (HFrEF) but a substantial gap exists for patients with HFpEF/HFmrEF. Despite the important role of the Renin-Angiotensin-Aldosterone System (RAAS) in heart failure pathophysiology, RAAS blockers were found ineffective for HFpEF patients. Indeed, even the new drug class of ARNI was found effective only in HFrEF patients. In this regard, a therapeutic alternative may be represented by drug stimulating the non-classic RAAS (ACE2 and A1-7) as well as other emerging drug classes (such as SGLT2 inhibitors). Reflecting on this global health burden and the gap in treatments among heart failure phenotypes, we summarize the leading players of heart failure pathophysiology, the available pharmacological treatments for each heart failure phenotype, and that in future development.

Surgical Lip Remodeling Following Permanent Filler Injection: A Scoping Review.

ABSTRACT: Over the years, several techniques have been introduced to obtain permanent lip enhancement, such as the use of silicone lip implants or the off-label use of permanent fillers. Although some reports indicate that permanent lip filler is safe, many others describe early- and late-onset complications. The main issue with permanent lip fillers is the lack of a standard technique to correct undesirable results. The aim of this scoping review was to list and evaluate the surgical pathways described in literature to correct lip deformity resulted from the injection of permanent fillers. The methods and the inclusion criteria of this work were specified in advance and documented in a protocol, according to the PRISMA 2009 checklist. The research was carried out on electronic databases PubMed, Cochrane Library, and Scopus databases identifying articles from March 1991 to December 2020 and conducted up to December 23rd, 2020. Articles language was limited to English. The selection process identified 3 retrospective studies eligible for inclusion. 73 patients and a total of 111 lips (72 upper and 39 lower) were considered. Two early complications were identified, 1 suture dehiscence and 1 total lip mucosa necrosis. Surgical lip remodeling following permanent filler injection seems to be an effective approach although the surgical pathway needs to be customized per each patient. Complication rate seems to be coherent to lip surgery performed with reconstructive purposes. To confirm these data case-control studies with much wider cohorts are needed to reach statistical significance.

Transvascular Hydrolysis of Hyaluronic Acid Filler With Hyaluronidase: An Ex Vivo Study.

BACKGROUND: Despite the favorable safety profile of hyaluronic acid (HA) dermal fillers, side effects can occur. Skin necrosis is one of the most severe early-occurring complications resulting from accidental vascular impairment. Hyaluronidase (HYAL) is commonly used to degrade HA chains, allowing the degraded product to pass through vessels, and thus relieving the vascular obstruction. OBJECTIVE: The purpose of this study is to evaluate, in an ex vivo setting, the capability of HYAL to degrade crosslinked HA that was injected into human vessels. MATERIALS AND METHODS: During a neck dissection, a portion of the anterior jugular vein and facial artery was harvested. The vein and artery specimens were filled with 25 mg/mL of crosslinked HA filler. Each specimen was soaked in 0.5 mL of HYAL (300 IU/mL), in its own test tube, for 4 hours, after which the remaining HA was quantified. RESULTS: The remaining HA volume was found to be 0.02 mL in the vein segment and 0.002 mL in the artery segment. CONCLUSION: A single administration of HYAL may not be adequate to restore blood flow in the event of embolism, and relatively high doses of this enzyme must be injected hourly into the affected tissue until resolution is complete.

Hyaluronic Acid Injections to Correct Lips Deformity Following Surgical Removal of Permanent Implant.

One of the most attractive areas of the face are the lips, they are crucial for emotion and communication, both during animation and at rest. Throughout the years, several techniques to obtain permanent lip enhancement have been introduced, such as the use of nonresorbable fillers. The main problem related to permanent fillers is that undesirable results could not always be repaired; although lip sequelae can be addressed surgically, some surgeons will not perform this type of procedure due to its complexity and the lack of guidelines.In this paper, the authors present a case of a labial incompetence developed after lips implant removal performed elsewhere; after clinical examination the patient was planned for surgery, although during preoperative instrumental examination (chest X-ray) a solitary pulmonary nodule was noted; further investigation performed with needle biopsy revealed a lung cancer. For this reason, the surgical procedure planned for lip restoration was not performed; however, the patient asked for a minimally invasive procedure, thus to improve, although temporarily, her lips appearance.For the aforementioned reasons, the patient was treated just with hyaluronic acid injections achieving a pleasant result, solving also the labial incompetence at rest.To the best of the author's knowledge, this paper represents the first one describing the use of hyaluronic acid injections to restore lip competence following surgical removal of permanent implant.

Skin Necrosis and Vision Loss or Impairment After Facial Filler Injection.

Purpose of the present study is to objectively evaluate the number of severe vascular complications, represented by skin necrosis and vision loss or impairment, following facial filler injection. The investigators implemented a review of the literature including articles published on PubMed database without limitation about year of publication, including all reports concerning skin necrosis and vision loss or impairment related to the injection of fillers for cosmetic uses. The search highlighted 45 articles and a total of 164 cases of skin necrosis and vision loss or impairment after injection of different substances. The injection site most frequently associated with complications was the nose (44.5%), followed by glabella (21%), nasolabial fold (15%), and forehead (10%). Results of the present study suggest that injectable filler can cause severe complications even in expertized hands. Treatments in the new defined "Dangerous triangle" must be carefully carried out. Despite our expectations, the highest rates of sever adverse events have been associated with autologous fat transfer practice.

Anti-Inflammatory Drugs as Anticancer Agents.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.

Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR-1-dependent pathway.

The aim of this study was to investigate whether telmisartan protects the heart from the ischaemia/reperfusion damage through a local microRNA-1 modulation. Studies on the myocardial ischaemia/reperfusion injury in vivo and on the cardiomyocyte hypoxia/reoxygenation damage in vitro were done. In vivo, male Sprague-Dawley rats administered for 3 weeks with telmisartan 12 mg/kg/d by gastric gavage underwent ischaemia/reperfusion of the left descending coronary artery. In these rats, infarct size measurement, ELISA, immunohistochemistry (IHC) and reverse transcriptase real-time polymerase chain reaction showed that expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and the protein Bcl-2 were significantly increased by telmisartan in the reperfused myocardium, paralleled by microRNA-1 down-regulation. In vitro, the transfection of cardiomyocytes with microRNA-1 reduced the expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2 in the cells. Telmisartan (50 µmol/L) 60 minutes before hypoxia/reoxygenation, while not affecting the levels of miR-1 in transfected cells in normoxic condition, almost abolished the increment of miR-1 induced by the hypoxia/reoxygenation to transfected cells. All together, telmisartan cardioprotected against the myocardial damage through the microRNA-1 modulation, and consequent modifications of its downstream target connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2.

Effect of nitric oxide reduction on arterial thrombosis.

OBJECTIVES: Nitric oxide (NO) represents the most powerful endogenous molecule with vasodilator action mainly produced by endothelial nitric oxide synthase (eNOS) enzyme. Polymorphisms and epigenetic-sensitive mechanisms can modulate the expression of eNOS gene, leading to the endothelial dysfunction. This review updates on the mechanistic role of NO in the regulation of platelet activation, as well as the impact of eNOS genetic and epigenetic modifications on arterial thrombosis onset. DESIGN: A systematic search was addressed to examination of PubMed databases with the following terms: nitric oxide; arterial thrombosis; endothelial dysfunction; DNA variations; epigenetic modifications; personalized therapy; network medicine. RESULTS: G894T, -786T/C, and 4b/4a variable number tandem repeat (VNTR), are the main classes of polymorphisms harbored in eNOS gene associated to increased arterial thrombosis risk. DNA methylation, histone/non-histone modifications, and microRNA (miRNAs) can modulate eNOS gene expression. Investigators largely focused on the role of miRNAs in modulating NO production in arterial thrombosis development. In detail, miR-195, and miR-582 are inversely correlated both to eNOS and NO levels, thus suggesting novel biomarkers. CONCLUSION: We are far from incorporating omics pathogenic data from bench to arterial thrombosis bedside. Network medicine is an emerging paradigm that ideally overcomes the current shortcomings of the reductionist approach. Despite several clinical limitations, the network-based analysis of the interactome might reveal the key nodes underlying the perturbations of the arterial thrombosis, thus advancing personalized therapy.

Postural Changes After Abdominoplasty in Morbid Obese Patients.

BACKGROUND: In the multidisciplinary treatment of obesity, the role of a plastic surgeon is to remove the excess of skin after weight loss to obtain cosmetic, functional, and psychological benefits. Obesity modifies body geometry, increases the mass of different segments, and imposes functional limitations in life activities that may predispose the obese to injury. The authors evaluated the postural conditions of obese patients, before and 12 months after surgery. METHODS: The study included 15 obese patients of both genders affected by class II obesity. Postural function was evaluated preoperatively and 12 months postoperatively. Patients underwent conventional abdominoplasty surgical procedure. In all patients, plantar pressure distribution and balance (stabilometric test) were evaluated before and 3 months after surgery. RESULTS: The static pedobarographic revealed a significant reduction in forefoot peak pressure; total plantar force; rearfoot plantar force percentage; midfoot plantar force percentage; and forefoot, midfoot, and rearfoot plantar contact areas percentage 3 months after surgery; the dynamic's one showed a reduction in the first metatarsal peak pressure and plantar contact. The stabilometric values showed a reduction in the range of center of foot pressure (CP) displacement along y axis, the average displacement of the CP speed from the mean (RMS y velocity), and CP mean peak in the condition of vision. CONCLUSIONS: Our study demonstrates the beneficial effect of dermolipectomies and the consequential weight loss on postural stability of obese men. Such findings may support the hypothesis that dermolipectomy may improve postural stability with and without vision. The data demonstrate that the benefits are related to the magnitude of the resected tissue.

Effects of Fat Grafting Containing Stem Cells in Microstomia and Microcheilia Derived from Systemic Sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease with multisystem involvement, dominated by a general fibrosis. The early stage of the disease is associated with progressive damage to microcirculation, particularly in the respiratory tract, the gastrointestinal tract and skin. The face assumes a typical appearance characterized by microstomia (reduction of mouth opening) and microcheilia (thinning of the lips). These conditions cause a considerable reduction in performance status of patients. We treated them by fat grafting, rich in adipose stem cells, and we evaluated through time clinical, functional and aesthetic evaluation of oral pathology associated with SSc. MATERIALS AND METHOD: From September 2014 to May 2016, we enrolled and treated seven patients in the plastic, reconstructive and aesthetic surgery clinic. Through time, we evaluated the following parameters: evaluation of mouth opening (maximum opening in superior-inferior and lateral directions) and lip thicknesses, both measured by doctors of the aforementioned operating unit; variation in the quality of life as perceived by patients according to the MHISS scale (Mouth Handicap Systemic Sclerosis); variation in severity of labial fibrosis assessed by microscopic analysis of pre- and post-fat transfer samples in the pathology clinic; safety of the protocol, according to the management of side effects resulting from the procedure; aesthetic evaluation, made by external observers and non-experts in the field, on pre- and post-operative photographs. RESULTS AND CONCLUSIONS: We reported satisfying results, both functionally and aesthetically, for all parameters except one, for which the sample size might have proven critical. These data should be a starting point for further experimental research and clinical trials. 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 .

Non-dermatophytic onychomycosis diagnostic criteria: an unresolved question.

Non-dermatophytic moulds (NDMs) have been increasingly recognised as causative agents of onychomycosis. The diagnosis of onychomycosis is most often obtained by microscopic observation of nail specimens where fungal elements can be detected and cultured by standard mycological techniques. Direct microscopic examination does not always result positive in NDM onychomycosis; therefore to perform a correct diagnosis, a proper mycological culture is often required. The purpose of our study was to evaluate the role of direct microscopic examination in the NDM onychomycosis diagnosis. The results show that only 57.2% of the specimens from onychomycosis patients could be properly diagnosed showing positivity to both direct microscopic examination and NDMs culture isolation in two or more subsequent inoculations, while 42.8% of analysed specimens with a negative direct microscopic examination, showed NDMs growth after three or more subsequent inoculations. The large proportion of false negatives (more than 42%) could be related to the duration of the infection and/or to the experience and skills of the personnel dedicated to specimen collection. We point out the need for thoroughly evaluating all specimens showing cultural growth in at least three subsequent medium inoculations, whatever the result of the microscopic examination, in order to reduce false-negative rates. This strategy would allow for more accurate diagnosis of this mycosis.

Structural insights into and activity analysis of the antimicrobial peptide myxinidin.

The marine environment has been poorly explored in terms of potential new molecules possessing antibacterial activity. Antimicrobial peptides (AMPs) offer a new potential class of pharmaceuticals; however, further optimization is needed if AMPs are to find broad use as antibiotics. We focused our studies on a peptide derived from the epidermal mucus of hagfish (Myxine glutinosa L.), which was previously characterized and showed high antimicrobial activity against human and fish pathogens. In the present work, the activities of myxinidin peptide analogues were analyzed with the aim of widening the original spectrum of action of myxinidin by suitable changes in the peptide primary structure. The analysis of key residues by alanine scanning allowed for the design of novel peptides with increased activity. We identified the amino acids that are of the utmost importance for the observed antimicrobial activities against a set of pathogens comprising both Gram-negative and Gram-positive bacteria. Overall, optimized bactericidal potency was achieved by adding a tryptophan residue at the N terminus and by the simultaneous substitution of residues present in positions 3, 4, and 11 with arginine. These results indicate that the myxinidin analogues emerge as an attractive alternative for treating drug-resistant infectious diseases and provide key insights into a rational design for novel agents against these pathogens.

Metabolic syndrome is associated with a poor outcome in patients affected by outflow tract premature ventricular contractions treated by catheter ablation.

BACKGROUND: The purpose of this study was to investigate the impact of metabolic syndrome (MS) on outcome of catheter ablation (CA) for treatment of frequent premature ventricular contraction beats (PVCs) originating from right ventricular outflow tract (RVOT), left ventricular outflow tract (LVOT) or coronary cusps (CUSPs), in patients with normal ventricular systolic function and absence of cardiac structural disease. METHODS: In this multicentre prospective study we evaluated 90 patients with frequent PVCs originating from RVOT (n = 68), LVOT (n = 19) or CUSPs (n = 3), treated with CA. According to baseline diagnosis they were divided in patients with MS (n = 24) or without MS (n = 66). The study endpoint was a composite of recurrence of acute or delayed outflow tract ventricular arrhythmia: acute spontaneous or inducible outflow tract ventricular arrhythmia recurrence or recurrence of outflow tract PVCs in holter monitoring at follow up. RESULTS: Patients with MS compared to patients without MS showed a higher acute post-procedural recurrence of outflow tract PVCs (n = 8, 66.6%, vs. n = 6, 9.0%, p = 0.005). At a mean follow up of 35 (17-43) months survival free of recurrence of outflow tract PVCs was lower in patients with baseline MS compared to patients without MS diagnosis (log-rank test, p < 0.001). In cox regression analysis, only MS was independently associated with study endpoint (HR = 9.655 , 95% CI 3.000-31.0.68 , p < 0.001). CONCLUSIONS: MS is associated with a higher recurrence rate of outflow tract PVCs after CA in patients without structural heart disease.

Extremely rare case of unilateral gigantomastia after hormonal stimulation treated with a modified wise pattern technique: A case report.

INTRODUCTION: Gigantomastia, characterized by excessive breast size (usually heavier than 2.5 kg), can result from various causes and significantly affect patients' lives. Surgical intervention is often required, and over time, several techniques have been developed for its treatment. These techniques aim to address the functional and aesthetic concerns associated with gigantomastia, providing relief to patients and improving their quality of life. PRESENTATION OF THE CASE: A 40-year-old primiparous housewife developed unilateral gigantomastia as a consequence of hormone therapy. To address this, a modified reduction mammoplasty procedure was undertaken, incorporating NAC (Nipple-Areola Complex) grafting. The reduction involved removing 3450 g of tissue, resulting in restored breast symmetry and enabling the patient to reintegrate into normal daily life. DISCUSSION: Compared to the traditional technique, the introduction of some modifications in the design allowed for the absence of complications such as dehiscence of the scar at the intersection of the T, the failure of the nipple graft attachment, and the maintenance of a conical shape over time, enabling complete symmetrization of the two breasts. CONCLUSION: The use of a modified version of the Thorek technique allowed for optimal functional and aesthetic restoration even in the case of a significantly disproportionate breast compared to the contralateral one, with no complications.

Comparative Analysis of Nipple Reconstruction Techniques: Five Flap vs. C-V Flap.

Background: Nipple-areola complex reconstruction represents the final phase in the comprehensive post-mastectomy treatment regimen. Despite the diversity of approaches available, there is currently no universally accepted benchmark technique for this critical aspect of breast reconstruction. In this study, we conducted a comparative assessment of two prominent techniques, the five Flap and C-V Flap. Materials and Methods: Between November 2016 and April 2023, we recruited 100 female patients who had undergone unilateral post-oncological mastectomy and divided them into two groups: Group A comprising 50 patients who underwent the 5-Flap technique, whereas Group B comprising the remaining 50 underwent the C-V Flap technique. Over a 6-month observation period, we assessed nipple projection loss and evaluated overall satisfaction through self-reporting by patients and independent assessments by a medical observer. Results: In our study, none of the reconstructed nipples in Group A (5 Flap) experienced either total or partial necrosis, contrasting with Group B (C-V Flap) which encountered a 10% incidence of partial necrosis and 4% incidence of total necrosis. Furthermore, the average nipple projection loss in Group B was substantial, measuring a 30% reduction from the initial projection at the 1-year mark, whereas Group A demonstrated a significantly lower 13% reduction. Notably, despite these variations in outcomes, both groups reported an equal and high level of satisfaction, with patients and external observers providing an average satisfaction score of 8.0 and 9.0, respectively. Conclusion: The five-flap technique represents a safe and effective approach for patients undergoing nipple reconstruction.

Precision medicine in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that has diverse clinical manifestations, ranging from restricted cutaneous involvement to life-threatening systemic organ involvement. The heterogeneity of pathomechanisms that lead to SLE contributes to between-patient variation in clinical phenotype and treatment response. Ongoing efforts to dissect cellular and molecular heterogeneity in SLE could facilitate the future development of stratified treatment recommendations and precision medicine, which is a considerable challenge for SLE. In particular, some genes involved in the clinical heterogeneity of SLE and some phenotype-related loci (STAT4, IRF5, PDGF genes, HAS2, ITGAM and SLC5A11) have an association with clinical features of the disease. An important part is also played by epigenetic varation (in DNA methylation, histone modifications and microRNAs) that influences gene expression and affects cell function without modifying the genome sequence. Immune profiling can help to identify an individual's specific response to a therapy and can potentially predict outcomes, using techniques such as flow cytometry, mass cytometry, transcriptomics, microarray analysis and single-cell RNA sequencing. Furthermore, the identification of novel serum and urinary biomarkers would enable the stratification of patients according to predictions of long-term outcomes and assessments of potential response to therapy.