Investigating Crimean-Congo haemorrhagic fever virus seropositivity in camels and human behavioural risks in an abattoir in Nigeria.

Crimean-Congo haemorrhagic fever virus (CCHFV) is an emerging viral pathogen with pandemic potential that is often misdiagnosed. Case fatality in low-resource settings could be up to 40% due to close contact between animals and humans. A two-year cross-sectional study was conducted in Fagge abattoir, Kano State, Nigeria, to estimate the seropositivity of CCHFV in camels using a commercial multi-species competitive enzyme-linked immunosorbent assay (ELISA). A closed-ended questionnaire was administered to the abattoir workers to assess their awareness, mitigation, and behavioural practices associated with CCHF. Of the 184 camels tested, 179 (97%) were seropositive for CCHFV (95% confidence interval (CI): 93.77, 99.11). The median (interquartile range (IQR)) age of respondents was 41 (35-52), with 62% having no education. Respondents had little knowledge about CCHFV and the concept of zoonotic disease. In this study, the high estimated prevalence of antibodies to CCHFV in camels highlights the heightened risk of transmission of CCHFV in Nigeria. Similarly, a concerning lack of knowledge and inadequate preventive practices, alongside a prevalence of high-risk behaviours associated with CCHF among abattoir workers, were noted in this study. Thus, there is an urgent need for comprehensive public health education and collaborative One Health strategies to avert the threats of spillover events.

Patient satisfaction with telemedicine in the Philippines during the COVID-19 pandemic: a mixed methods study.

BACKGROUND: The capacity to deliver essential health services has been negatively impacted by the COVID-19 pandemic, particularly due to lockdown restrictions. Telemedicine provides a safe, efficient, and effective alternative that addresses the needs of patients and the health system. However, there remain implementation challenges and barriers to patient adoption in resource-limited settings as in the Philippines. This mixed methods study aimed to describe patient perspectives and experiences with telemedicine services, and explore the factors that influence telemedicine use and satisfaction. METHODS: An online survey consisting of items adapted from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Clinician & Group Adult Visit Survey 4.0 (beta) and the Telehealth Usability Questionnaire (TUQ) was completed by 200 participants aged 18 to 65 years residing in the Philippines. A subsample of 16 participants was interviewed to provide further insights on their experiences. We used descriptive statistics to analyze survey data and thematically analyzed data from interviews guided by the principles of grounded theory. RESULTS: Participants were generally satisfied with telemedicine, and found it to be an efficient and convenient means of receiving healthcare. About 3 in 5 perceived telemedicine as affordable, with some finding telemedicine costs to be high and comparable to in-person consultations. Our results suggest that participants preferred telemedicine services, especially in cases where they feel that their condition is not urgent and does not need extensive physical examination. Safety against COVID-19, privacy, accessibility, and availability of multiple communication platforms contributed to patient satisfaction with telemedicine. Negative perceptions of patients on quality of care and service related to their telemedicine provider, inherent limitations of telemedicine in the diagnosis and management of patients, perceived high costs especially for mental health conditions, and poor connectivity and other technological issues were barriers to telemedicine use and satisfaction. CONCLUSION: Telemedicine is viewed as a safe, efficient, and affordable alternative to receiving care. Expectations of patients on costs and outcomes need to be managed by providers to increase satisfaction. Continued adoption of telemedicine will require improvements in technology infrastructure and technical support for patients, training and performance evaluation of providers to ensure quality of care and service, better patient communication to meet patient needs, and integration of telemedicine services in remote areas that have limited access to medical services. Telemedicine, to realize its full potential, should be centered in health equity - addressing patient barriers and needs, reducing health disparities across population groups and settings, and providing quality services to all.

Uncoiled linear looped vessels in basal cell carcinoma: a novel morphology.

We describe two cases of nodular basal cell carcinoma presenting with novel morphology of linear looped hairpin vessels under dermoscopy.

Giant congenital fibroepithelial polyp of the scrotum.

Fibroepithelial polyps are common tumors of mesodermal origin. However, only a few case reports of giant fibroepithelial polyps have been published, and they have mainly involved adults. This case report describes a 3-month-old boy with a pedunculated mass in the scrotum. To our knowledge, this is the first report of a giant congenital fibroepithelial polyp on this location.

The Antiedematous Effect of Exogenous Lactate Therapy in Traumatic Brain Injury: A Physiological and Mechanistic Approach.

BACKGROUND: Sodium lactate (SL) has been described as an efficient therapy in treating raised intracranial pressure (ICP). However, the precise mechanism by which SL reduces intracranial hypertension is not well defined. An antiedematous effect has been proposed but never demonstrated. In this context, the involvement of chloride channels, aquaporins, or K-Cl cotransporters has also been suggested, but these mechanisms have never been assessed when using SL. METHODS: In a rat model of traumatic brain injury (TBI), we compared the effect of SL versus mannitol 20% on ICP, cerebral tissue oxygen pressure, and brain water content. We attempted to clarify the involvement of chloride channels in the antiedematous effects associated with lactate therapy in TBI. RESULTS: An equimolar single bolus of SL and mannitol significantly reduced brain water content and ICP and improved cerebral tissue oxygen pressure 4 h after severe TBI. The effect of SL on brain water content was much longer than that of mannitol and persisted at 24 h post TBI. Western blot and immunofluorescence staining analyses performed 24 h after TBI revealed that SL infusion is associated with an upregulation of aquaporin 4 and K-Cl cotransporter 2. CONCLUSIONS: SL is an effective therapy for treating brain edema after TBI. This study suggests, for the first time, the potential role of chloride channels in the antiedematous effect induced by exogenous SL.

Insight into the microphysics of antigorite deformation from spherical nanoindentation.

The mechanical behaviour of antigorite strongly influences the strength and deformation of the subduction interface. Although there is microstructural evidence elucidating the nature of brittle deformation at low pressures, there is often conflicting evidence regarding the potential for plastic deformation in the ductile regime at higher pressures. Here, we present a series of spherical nanoindentation experiments on aggregates of natural antigorite. These experiments effectively investigate the single-crystal mechanical behaviour because the volume of deformed material is significantly smaller than the grain size. Individual indents reveal elastic loading followed by yield and strain hardening. The magnitude of the yield stress is a function of crystal orientation, with lower values associated with indents parallel to the basal plane. Unloading paths reveal more strain recovery than expected for purely elastic unloading. The magnitude of inelastic strain recovery is highest for indents parallel to the basal plane. We also imposed indents with cyclical loading paths, and observed strain energy dissipation during unloading-loading cycles conducted up to a fixed maximum indentation load and depth. The magnitude of this dissipated strain energy was highest for indents parallel to the basal plane. Subsequent scanning electron microscopy revealed surface impressions accommodated by shear cracks and a general lack of dislocation-induced lattice misorientation. Based on these observations, we suggest that antigorite deformation at high pressures is dominated by sliding on shear cracks. We develop a microphysical model that is able to quantitatively explain Young's modulus and dissipated strain energy data during cyclic loading experiments, based on either frictional or cohesive sliding of an array of cracks contained in the basal plane. This article is part of a discussion meeting issue 'Serpentinite in the earth system'.

Stages of Change for Mammography Among Mexican Women and a Decisional Balance Comparison Across Countries.

An analysis of the adoption of secondary preventive behaviors is significant in regions with disparities in mammography use and breast cancer survival. Therefore, we determined the cognitive factors and the degree to which they differentiate stages of change in mammography among Mexican women. We also compared the decisional balance performance at Mexico, Switzerland, South Korea, and the USA. A cross-sectional study was designed for women in the stages of precontemplation (n = 240), contemplation (n = 243), action (n = 205), maintenance (n = 311), and relapse (n = 348). We only considered those ≥40 years with no cancer history. We measured the pros, cons, and self-efficacy, among other components. The decisional balance was estimated, and the result was transformed into T-scores. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with multinomial logistic regression using precontemplation as the reference group. The decisional balance distinguished stages partially: in contemplation, the OR was 1.26 (95%CI 1.08, 1.47) and in maintenance, 1.34 (95%CI 1.13, 1.59); in action and relapse, the statistical significance was marginal (p < 0.10). The decisional balance T-score performance registered variations among countries. Additionally, the effect of self-efficacy progressively ascended from contemplation to action and maintenance (OR = 1.29 [95%CI 1.05, 1.58], 1.53 [95%CI 1.20, 1.96], and 2.48 [95%CI 1.82, 3.39], respectively). Furthermore, risk perception and severity did not have an effect on stages of change among Mexican women. Recognition of what provokes action in a population is a key factor in the efficacy of screening programs. Variations among countries highlight the necessity for importance of investigating cognitive determinants for mammography in specific areas.

Results of Perilunate Dislocations and Perilunate Fracture Dislocations With a Minimum 15-Year Follow-Up.

PURPOSE: To evaluate the long-term clinical, functional, and radiological outcomes in 30 patients with at least 15 years of follow-up. METHODS: We performed a retrospective study that identified 73 patients. Thirty patients agreed to participate and were included. The mean follow-up was 18 years (range, 15-24 years). There were 14 cases of perilunate dislocation and 16 cases of perilunate fracture-dislocation (including 13 transscaphoid perilunate fracture-dislocations). At the last follow-up, the clinical and functional evaluation was based on the range of motion, grip strength, the Mayo wrist score, the Quick Disabilities of the Arm Shoulder and Hand score, and the Patient-Rated Wrist Evaluation score. Radiological abnormalities, according to the Herzberg classification, were 5 type A1 cases, 7 type B, 16 type B1, and 2 type C. RESULTS: The mean flexion-extension arc, radial-ulnar abduction arc, and pronation-supination arc were, respectively, 68%, 67%, and 80%, relative to the contralateral side. The mean grip strength was 70%, relative to the contralateral side. The mean Mayo wrist score was 70, and the mean Quick Disabilities of the Arm Shoulder and Hand and Patient-Rated Wrist Evaluation scores were, respectively, 20 and 21. Five patients had secondary procedure. Six patients had a complex regional pain syndrome type 1. CONCLUSIONS: Although arthritis occurred in 70% of cases, its clinical and functional impact appeared to be low. However, the 2 lowest Mayo wrist scores corresponded to the patients with the most advanced arthritis. Complex regional pain syndrome appeared to have an impact on long-term outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

A postoperative heterotopic ossification leading to radial palsy.

We report the case of a 58-year-old man who developed radial palsy three months after surgical reinsertion of the distal biceps brachii through a single anterior approach. Radiographs and ultrasound examinations revealed heterotopic ossification compressing the deep branch of the radial nerve. Surgical excision and neurolysis were performed. At the two-month follow-up, the patient was asymptomatic. Practitioners and orthopedic surgeons should be aware of the risk of heterotopic ossification after distal biceps reinsertion and its possible atypical clinical presentation.

New radiographic monitoring indices for total trapeziometacarpal prostheses.

OBJECTIVE: The objective of this study is to propose and evaluate a method of monitoring implants via the calculation of a trapezial and metacarpal index from radiological measurements and to describe an initial patient analysis. METHODS: This retrospective study describes the trapezial index which reflects the trapezial bone stock not occupied by the trapezial cup, while the metacarpal index reflects the rate of metacarpal occupation by the prosthetic stem. Those indexes were used on a series of 20 patients with a Maïa™ prosthesis with a minimum follow-up of seven years. The indexes were measured immediately postoperatively and at the various annual check-ups. Four observers measured each index on two occasions, to obtain an inter- and intra-observer correlation coefficient. RESULTS: The average intra-observer correlation coefficient for the trapezium index was 0.94, for the metacarpal index 0.98. The inter-observer correlation coefficient was 0.93 for the trapezium index, 0.94 for the metacarpal index on average. The post-hoc calculated power was 0.98 as the number of subjects required was not usable. The mean immediate postoperative trapezial index was 45.74%, compared with a value at longest follow-up of 41.74%, reflecting a highly significant loss of height of 8,74%. The mean immediate postoperative metacarpal index was 77.69% compared with a mean value at longest follow-up of 78.99% indicating a non-significant increase in the index of 1,67%. CONCLUSION: Proposed indexes had excellent inter- and intra-observer correlation, the metacarpal one is stable over time whereas the trapezial one reveals changes in some patients, requiring further investigations. These simple and reproducible indexes allow precise monitoring of trapeziometacarpal prostheses and identify radiographic changes that should lead to additional examinations to improve survival of implants. LEVEL OF EVIDENCE: III, retrospective single cohort study.

Association of rs4711998 of IL-17A, rs2275913 of IL-17A and rs763780 IL-17F gene polymorphisms with non-segmental vitiligo in a Mexican population.

Vitiligo is the most common depigmenting disease characterized by achromic macules due to selective loss of melanocytes. The pathogenesis remains poorly elucidated, and multiple hypotheses exist regarding its pathogenesis. Evidence suggests that stress on melanocytes can result in activation of the immune system, and involvement of both activated cluster of differentiation (CD8+) cytotoxic and CD4+ T cells in the dysfunction, depigmentation, and apoptosis of melanocytes. Recent studies show that the interleukin 17 (IL-17) axis plays a central role in the pathogenesis of the disease. IL-17 is an important regulatory effector cytokine in this pathway. The aim of this study was to evaluate the association of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) with vitiligo in a Northeastern Mexican population. This was a case-control study and included 116 patients with vitiligo and 116 control subjects. Genotype characterization of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A p ≤ 0.05 was considered significant. It was observed that the combination of the genotypes GG/GA for IL-17F rs763780 (7488A/G) was associated with an increased risk for the development of vitiligo (OR 2.0943, 95% Cl 1.2375-3.5445, p = 0.0056). Regarding IL-17A rs4711998 (-832A/G) and IL-17A rs2275913 (-197G/A) genotyping, no association with vitiligo development was found. In conclusion, the SNP rs763780 in the IL-17F gene appears to be a risk factor for vitiligo development in this Mexican population and it may be useful in future studies, especially for the development of new therapies.

Massive Facial Presentation of Dermatofibrosarcoma Protuberans.

Dermatofibrosarcoma protuberans is a low-grade cutaneous sarcoma typically located on the trunk or proximal extremities. Less common locations include the head, face, and neck area. This tumour is slow growing with variable clinical appearance. It is known for its locally invasive nature and low metastatic propensity. Because imaging findings are rather nonspecific, biopsy is needed for definite diagnosis. This case describes an unusually large example of dermatofibrosarcoma protuberans in the less common preauricular region.

Association between the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants with vitiligo: study on a Mexican population.

BACKGROUND: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. OBJECTIVE: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. METHODS: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. RESULTS: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). CONCLUSION: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.

Experimental study to assess the impact of vasopressors administered during maintenance of the brain-dead donation in the quality of the intestinal graft.

BACKGROUND: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model. METHODS: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3+ counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10. RESULTS: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3+ mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE (p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver (p ˂ 0.01). CONCLUSION: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.

BACKGROUND: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model. METHODS: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3 + counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10. RESULTS: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3 + mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE ( p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver ( p ˂ 0.01). CONCLUSION: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.

Impact of pharmacist-led care on glycaemic control of patients with uncontrolled type 2 diabetes: a randomised controlled trial in Nigeria.

BACKGROUND: Diabetes mellitus is a chronic, degenerative disease, requiring a multi-dimensional, multi-professional care by healthcare providers and substantial self-care by the patients, to achieve treatment goals. OBJECTIVE: To evaluate the impact of pharmacist-led care on glycaemic control in patients with uncontrolled Type 2 Diabetes. METHODS: In a parallel group, single-blind randomised controlled study; type 2 diabetic patients, with greater than 7% glycated haemoglobin (A1C) were randomised into intervention and usual care groups and followed for six months. Glycated haemoglobin analyzer, lipid analyzer and blood pressure monitor/apparatus were used to measure patients' laboratory parameters at baseline and six months. Intervention group patients received pharmacist-structured care, made up of patient education and phone calls, in addition to usual care. In an intention to treat analysis, Mann-Whitney U test was used to compare median change at six months in the primary (A1C) and secondary outcome measures. Effect size was computed and proportion of patients that reached target laboratory parameters were compared in both arms. RESULTS: All enrolled participants (108) completed the study, 54 in each arm. Mean age was 51 (SD 11.75) and majority were females (68.5%). Participants in the intervention group had significant reduction in A1C of -0.75%, compared with an increase of 0.15% in the usual care group (p<0.001; eta-square= 0.144). The proportion of those that achieved target A1C of <7% at 6 months in the intervention and usual care group was 42.6% vs 20.8% (p=0.02). Furthermore, intervention patients were about 3 times more likely to have better glucose control; A1C<7% (aOR 2.72, 95% CI: 1.14-6.46) compared to usual care group, adjusted for sex, age, and duration of diabetes. CONCLUSIONS: Pharmacist-led care significantly improved glycaemic control in patients with uncontrolled T2DM.

A systematic review of cranioplasty material toxicity in human subjects.

PURPOSE: Local and systemic toxic reactions to implanted materials can result in morbidities. However, little is reported about cranioplasty implants. Therefore, we performed a systematic review on the toxicity of different materials used for cranioplasty implants. MATERIALS AND METHODS: A systematic search was conducted by browsing the Pubmed, Embase, and Cochrane Library databases. All human studies that identified toxic (aseptic) reactions to any types of material used as cranioplasty implants or onplants, published up to January 1, 2019, were included in the review. RESULTS: Nineteen studies were identified. Collectively, 36 patients endured some type of toxic reaction to an implanted material. Eleven studies presented several types of toxicity for PMMA cranioplasties in several tissue types. One article highlighted the risk of neurotoxicity for PMMA cranioplasty. Three articles presented toxic reactions to calcium phosphate and titanium implants. Three additional articles presented toxic reactions to PEEK, polypropylene-polyester, and polyethylene. CONCLUSION: All materials currently used for cranioplasty showed occasional toxicity and morbidities. Therefore, none can be considered completely biologically inert. We found that aseptic inflammatory reactions have been underreported in the literature due to a high incidence of infections with questionable evidence.

Vaccine Hesitancy Against SARS-CoV-2 in Health Personnel of Northeastern Mexico and Its Determinants.

With the emergence of effective vaccines against SARS-CoV-2, the need to find the determinants for its correct distribution is created, with health personnel being an essential group where coverage must be ensured. MATERIALS AND METHODS: A cross-sectional study was conducted through an electronic survey that was distributed to health personnel in the state of Nuevo Leon, Mexico. Potential determinants for vaccine hesitancy were covered including their intention to be vaccinated against SARS-CoV-2. RESULTS: A total of 543 responses were collected from health professionals, which 30 (5.5%) of the subjects stated that they would reject SARS-CoV-2 vaccination. How well informed the subjects were was the most determining factor, where misinformation related to vaccination and COVID-19 was the most important cause of vaccine rejection. CONCLUSION: The implementation of educational strategies for health personnel are required.

Netherton Syndrome: Case Report and Review of the Literature.

Netherton syndrome (NS) is a rare genodermatosis with an autosomal recessive pattern of inheritance caused by pathogenic variants in the SPINK5 gene. It is characterized by a triad consisting of atopic diathesis, ichthyosis linearis circumflexa, and hair shaft abnormalities. Ichthyosis linearis circumflexa can be confused with atopic dermatitis leading to a delayed diagnosis. Furthermore, difficulty in making the differential diagnosis with other atopiform, erythrodermic, and ichthyosiform entities that exhibit hair shaft abnormalities represent a challenge. Trichoscopy is an accessible and noninvasive auxiliary diagnostic tool in these cases; the hair shaft abnormalities found in NS are bamboo, golf tee, and matchstick hairs. Identification of a pathogenic variant in the SPINK5 gene through genetic testing is necessary to confirm the diagnosis. Multiple treatment options are available including topical therapy with emollients, corticosteroids, calcineurin inhibitors, antiseptics, and narrowband UVB phototherapy. Systemic treatments comprehend intravenous immunoglobulins, and advances in the understanding of the pathophysiology of NS have led to more directed therapies with biologics such as infliximab, ixekizumab, secukinumab, ustekinumab, and dupilumab. Treatments currently under investigation include inhibitors of kallikrein 5, cathelicidins, drugs activating the transcription factor nuclear factor erythroid-derived 2-like 2, and gene therapy using autologous keratinocytes induced with a lentiviral vector encoding SPINK5.