Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data.

BACKGROUND: Urologic chronic pelvic pain syndrome (UCPPS), which includes interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis (CP/CPPS), is associated with increased voiding frequency, nocturia, and chronic pelvic pain. The cause of these diseases is unknown and likely involves many different mechanisms. Dysregulated renin-angiotensin-aldosterone-system (RAAS) signaling is a potential pathologic mechanism for IC/BPS and CP/CPPS. Many angiotensin receptor downstream signaling factors, including oxidative stress, fibrosis, mast cell recruitment, and increased inflammatory mediators, are present in the bladders of IC/BPS patients and prostates of CP/CPPS patients. Therefore, we aimed to test the hypothesis that UCPPS patients have dysregulated angiotensin signaling, resulting in increased hypertension compared to controls. Secondly, we evaluated symptom severity in patients with and without hypertension and antihypertensive medication use. METHODS: Data from UCPPS patients (n = 424), fibromyalgia or irritable bowel syndrome (positive controls, n = 200), and healthy controls (n = 415) were obtained from the NIDDK Multidisciplinary Approach to the Study of Chronic Pelvic Pain I (MAPP-I). Diagnosis of hypertension, current antihypertensive medications, pain severity, and urinary symptom severity were analyzed using chi-square test and t-test. RESULTS: The combination of diagnosis and antihypertensive medications use was highest in the UCPPS group (n = 74, 18%), followed by positive (n = 34, 17%) and healthy controls (n = 48, 12%, p = 0.04). There were no differences in symptom severity based on hypertension in UCPPS and CP/CPPS; however, IC/BPS had worse ICSI (p = 0.031), AUA-SI (p = 0.04), and BPI pain severity (0.02). Patients (n = 7) with a hypertension diagnosis not on antihypertensive medications reported the greatest severity of pain and urinary symptoms. CONCLUSION: This pattern of findings suggests that there may be a relationship between hypertension and UCPPS. Treating hypertension among these patients may result in reduced pain and symptom severity. Further investigation on the relationship between hypertension, antihypertensive medication use, and UCPPS and the role of angiotensin signaling in UCPPS conditions is needed.

NB-UVB plus oral Polypodium leucotomos extract display higher efficacy than NB-UVB alone in patients with vitiligo.

Polypodium leucotomos displayed a synergic effect with NB-UVB in psoriasis, but its application on vitiligo remains understudied. The aim of this study was to investigate whether oral supplementation with leaves extract of Polypodium leucotomos (PL) improves narrow band (NB) UVB phototherapy-induced repigmentation. Forty-four patients with generalized vitiligo were enrolled in this randomized, prospective, placebo controlled study. Twenty-three patients were randomly selected to receive combined treatment with NB-UVB phototherapy and 480 mg oral PL twice daily while 21 patients received NB-UVB phototherapy combined with placebo. All subjects were treated with NB-UVB twice weekly for 6 months. Our results demonstrated that oral PL combined with NB-UVB improved repigmentation as well as increased the response rate compared with patients treated with NB-UVB alone (47.8% vs 22%). Our study suggests that oral supplementation of PL and NB-UVB phototherapy enhance the extent of repigmentation.

Can intermittent, time-restricted circadian fasting modulate cutaneous severity of dermatological disorders? Insights from a multicenter, observational, prospective study.

The impact of intermittent circadian fasting (ICF) on skin disorders is far to be plenty deciphered. However, the circadian rhythm seems to exert a modulation on dermatoses severity, drug-response, and drug-related side effects. We aimed to evaluate ICF effect in the daily management of dermatological diseases. In this multicenter, prospective observational study we enrolled patients willing to undergo the 2018 ICF (from May 16 to June 14). Dermatoses severity were evaluated at the beginning of ICF (T0) and at the end of ICF (T1) by two independent board-certified dermatologists. Seventy-two patients suffering from different dermatoses volunteered to take part into the study. They displayed a mean age of 40.38 ± 12.46 years (median 41.0 years), 25 subjects were males (34.7% of the entire sample). The median weight change was 0 kg. The overall ICF effect size was -0.58 ([95% CI -0.83 to -0.33], P < .0001, medium effect size). Since in the present investigation no weight loss occurred, we could speculate that the impact of fasting in terms of improvements in the clinical symptoms could be rather due to the perturbation of the human biological clock. Despite our data remain preliminary, a chronobiological approach should be incorporated in the dermatological armamentarium.

The Association between Alopecia and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

IMPORTANCE: The link between autoimmune gut disorders and different types of hair loss conditions has been recently investigated with an increased interest. With acknowledgement of the connection between immune dysregulation and the gut microbiome, this pathway is now becoming recognized as playing an important role in hair growth. The inflammatory cascade that results from the disruption of gut integrity such as seen in inflammatory bowel diseases (IBD) has been associated with certain types of alopecia. OBJECTIVE: The aim of this work was to evaluate the association between alopecia and IBD. EVIDENCE REVIEW: A primary literature search was conducted using the PubMed, Embase, and Web of Science databases to identify articles on co-occurring alopecia and IBD from 1967 to 2020. A total of 79 studies were included in the review. A one-way proportional meta-analysis was performed on 19 of the studies to generate the pooled prevalence of alopecia and IBD. FINDING: The pooled prevalence of non-scarring alopecia among IBD patients was 1.12% (k = 7, I2 = 98.6%, 95% CI 3.1-39.9); the prevalence of IBD among scarring and non-scarring alopecia was 1.99% (k = 12; I2 = 99%, 95% CI 6.2-34). The prevalence of non-scarring alopecia areata (AA) among IBD was compared to the prevalence of AA in the general population (0.63 vs. 0.1%; p < 0.0001). Similarly, the prevalence of IBD among the scarring and non-scarring alopecia groups was compared to the prevalence of IBD in the general population (1.99 vs. 0.396%; p = 0.0004). CONCLUSION: IBD and alopecia, particularly AA, appear to be strongly associated. Dermatology patients with alopecia may benefit from screening for IBD.

Pure and Mixed Desmoplastic Melanomas: A Retrospective Clinicopathologic Comparison of 33 Cases.

BACKGROUND: Pure and mixed desmoplastic melanomas (DMs) may have different natural histories and behaviors. METHODS: We conducted a retrospective review of patients diagnosed with DM at our institution between January 1997 and April 2019. A total of 33 unique DMs were identified and subsequently analyzed based on the histologic type (pure vs. mixed). RESULTS: The majority (57.6%) of our cases were classified as pure histology. Patients with pure DMs were more likely to be men (P = 0.035) and be older than 65 years (P = 0.019) compared with patients with mixed DMs. Patients with mixed DM were more likely to have mitoses present (P = 0.001) compared with patients with pure DM. There were no differences in ulceration, perineural invasion, vascular invasion, or survival between patients with pure and mixed histologic subtypes. In addition, no differences in sentinel lymph node biopsy, radiation, or chemotherapy were noted between the 2 histologic subtypes. Immunohistochemistry showed that 27.3% of the pure DMs stained with Melan-A and HMB45 were positive for these immunomarkers. CONCLUSIONS: Pure and mixed variants of DM were found to have similar clinicopathologic characteristics. Patients with the mixed histologic subtype were more likely to have mitoses, but no difference in the therapeutic management or patient survival was seen between the 2 subtypes.

Racial differences in time to treatment for melanoma.

BACKGROUND: Longer time from diagnosis to definitive surgery (TTDS) is associated with increased melanoma-specific mortality. Although black patients present with later-stage melanoma and have worse survival than non-Hispanic white patients, the association between race and TTDS is unknown. OBJECTIVE: To investigate racial differences in time to melanoma treatment. METHODS: Retrospective review of the National Cancer Database (2004-2015). Multivariable logistic regression was used to evaluate the association of race with TTDS, controlling for sociodemographic/disease characteristics. RESULTS: Of the 233,982 patients with melanoma identified, 1221 (0.52%) were black. Black patients had longer TTDS for stage I to III melanoma (P < .001) and time to immunotherapy (P = .01), but not for TTDS for stage IV melanoma or time to chemotherapy (P > .05 for both). When sociodemographic characteristics were controlled for, black patients had over twice the odds of having a TTDS between 41 and 60 days, over 3 times the odds of having a TTDS between 61 and 90 days, and over 5 times the odds of having a TTDS over 90 days. Racial differences in TTDS persisted within each insurance type. Patients with Medicaid had the longest TTDS (mean, 60.4 days), and those with private insurance had the shortest TTDS (mean, 44.6 days; P < .001 for both). CONCLUSIONS: Targeted approaches to improve TTDS for black patients are integral in reducing racial disparities in melanoma outcomes.

Incidence and outcomes of cutaneous angiosarcoma: A SEER population-based study.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, malignant tumor of vascular mesenchymal origin accounting for less than 1% of all sarcomas. OBJECTIVE: To examine epidemiologic trends and outcomes in CAS. METHODS: In this retrospective, population-based study, patients with CAS were identified from the Surveillance Epidemiology and End Results database. Age, sex, and race-standardized incidence rates (IRs) were calculated. Survival was assessed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 811 patients with CAS, 43% had a prior primary cancer. CAS IR for patients without prior primary cancers dropped from 5.88 per 100,000 in 1973 to 1984 to 2.87 per 100,000 in 2005 to 2014. In those with prior primary cancers, IR rose from 0.03 per 100,000 in 1973 to 1984 to 2.25 per 100,000 in 2005 to 2014. On multivariate analysis, patients older than 70 years of age had a higher risk of death compared with those younger than 50 years (hazard ratio, 2.16; 95% confidence interval 1.33-3.57; P = .002), and distant disease was associated with increased risk of death compared with localized disease (hazard ratio, 1.50; 95% confidence interval, 1.11-2.03; P = .008). Receipt of surgery and/or radiation therapy was not associated with survival. LIMITATIONS: Potential selection and miscoding bias, retrospective nature. CONCLUSION: CAS rates are rising among those with other prior primary cancers. Survival is not affected by current therapeutic strategies, highlighting the need for additional treatment options.

Therapeutic Plasma Exchange: A potential Management Strategy for Critically Ill COVID-19 Patients.

In the 5 months since initial reports of COVID-19 came to light, the death toll due to SARS-CoV-2 has rapidly increased. The morbidity and mortality of the infection varies based upon patient age, comorbid conditions, viral load, and the availability of effective treatments. Findings from limited autopsies, clinical observations, and laboratory data suggest that high cytokine levels and a procoagulant state can precipitate acute respiratory distress syndrome and multi-organ dysfunction syndrome in critically ill patients. To complicate matters, comorbidities may affect the response to medical treatments currently in use, all of which are still in trial phase. Therapeutic plasma exchange (TPE) merits consideration in the treatment of critically ill COVID-19 patients and is an avenue for clinical trials to pursue. If efficacious, faster recovery of patients may lead to shorter intensive care unit stays and less time on mechanical ventilation. Herein, we briefly discuss some of the various approaches currently being investigated for the treatment of SARS-CoV-2 with a focus on potential benefits of TPE for selected critically ill patients.

Predicting Secukinumab Fast-Responder Profile in Psoriatic Patients: Advanced Application of Artificial-Neural-Networks (ANNs).

BACKGROUND: Drug resistance to biologics in psoriasis therapy can occur – it may be acquired during a treatment or else present itself from the beginning. To date, no biomarkers are known that may reliably guide clinicians in predicting responsiveness to biologics. Biologics may pose a substantial economic burden. Secukinumab efficiently targets IL-17 in the treatment of psoriasis. OBJECTIVE: To assess the “fast responder” patient profile, predicting it from the preliminary complete blood count (CBC) and clinical examination. MATERIALS AND METHODS: From November 2016 to May 2017 we performed a multicenter prospective open label pilot study in three Italian reference centers enrolling bio-naive plaque psoriasis patients, undergoing the initiation phase secukinumab treatment (300mg subcutaneous at week 0,1,2,3,4). We define fast responders as patients having achieved at least PASI 75 at the end of secukinumab induction phase. Clinical and CBC data at week 0 and at week 4 were analyzed with linear statistics, principal component analysis, and artificial neural networks (ANNs), also known as deep learning. Two different ANNs were employed: Auto Contractive Map (Auto-CM), an unsupervised ANNs, to study how this variables cluster and a supervised ANNs, Training with Input Selection and Testing (TWIST), to build the predictive model. RESULTS: We enrolled 23 plaque psoriasis patients: 19 patients were responders and 4 were non-responders. 30 attributes were examined by Auto-CM, creating a semantic map for three main profiles: responders, non-responders and an intermediate profile. The algorithm yielded 5 of the 30 attributes to describe the 3 profiles. This allowed us to set up the predictive model. It displayed after training testing protocol an overall accuracy of 91.88% (90% for responders and 93,75% for non-responders). CONCLUSIONS: The present study is possibly the first approach employing ANNs to predict drug efficacy in dermatology; a wider use of ANNs may be conducive to useful both theoretical and clinical insight. J Drugs Dermatol. 2020;19(12) doi:10.36849/JDD.2020.5006.

Omalizumab in Chronic Urticaria: An Italian Survey.

Omalizumab is approved for use in chronic spontaneous urticaria (CSU); however, it is not approved for chronic inducible urticaria (CIndU). The aim of the present study was to assess the effectiveness of omalizumab in treating CSU and CIndU in Italy. This is a multicentre prospective observational real-life study involving patients with severe urticaria capable of undergoing omalizumab therapy. We enrolled 127 patients (59.1% females), ranging in age from 15 to 83 years, 69.3% had CSU alone, 26.8% had CSU and CIndU, and 3.9% had only CIndU (30.8% delayed pressure, 35.9% dermographic, 15.3% cholinergic, 12.8% cold, 5.1% aquagenic). After the first cycle of omalizumab (300 mg every 4 weeks for 24 weeks), 16 CSU patients and 10 patients (20.5%) with CIndU with or without CSU did not require a second cycle of omalizumab (300 mg every 4 weeks for 20 weeks). The patient with aquagenic urticaria achieved remission after the first cycle. None showed a lack of response to the second cycle of omalizumab. Omalizumab is a promising drug for both spontaneous and inducible chronic urticaria. Current evidence indicates that omalizumab may be approved also for CIndU.

Predictors of sentinel lymph node positivity in thin melanoma using the National Cancer Database.

BACKGROUND: Sentinel lymph node biopsy (SLNB) specimens are often obtained from patients for further staging after these patients have undergone melanoma excision. Limited data regarding predictors of SLNB positivity in thin melanoma are available. OBJECTIVE: We sought to evaluate predictors of SLNB positivity in thin melanoma. METHODS: Patients with cutaneous melanoma with a Breslow thickness ≤1.00 mm who received a SLNB were identified from the National Cancer Database between 2004 and 2014 (n = 9186). Predictors of SLNB positivity were analyzed using logistic regression. RESULTS: In a multivariate analysis, patients <60 years of age (P < .001) and Breslow thickness >0.8 mm (P = .03) were at increased risk for positive sentinel lymph node (SLN). Moreover, on multivariate analysis, the presence of dermal mitoses increased the odds of SLN positivity by 95% (odds ratio [OR] 1.95 [95% confidence interval {CI} 1.53-2.5], P < .001), ulceration by 63% (OR 1.63 [95% CI 1.21-2.18], P < .001), and Clark level IV to V by 48% (OR 1.48 [95% CI 1.19-1.85]). Patients without ulceration but with dermal mitoses had 92% (OR 1.92 [95% CI 1.5-2.48], P < .001) increased SLN positivity. LIMITATIONS: Limited survival data are available. CONCLUSIONS: Younger age, a Breslow thickness >0.8 mm, the presence of dermal mitoses, ulceration, and Clark level IV to V are positive predictors of positive SLN. While the new American Joint Committee on Cancer system has removed dermal mitotic rate from staging, continued evaluation of dermal mitotic rate could be valuable for guiding surgical decision making about SLNB.

Sentinel lymph node biopsy in Merkel cell carcinoma: Predictors of sentinel lymph node positivity and association with overall survival.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive malignancy with high rates of recurrence and metastasis. OBJECTIVE: To evaluate predictors of sentinel lymph node (SLN) positivity in MCC using the National Cancer Database. METHODS: The National Cancer Database, from 2012 to 2014, was used to identify 3048 patients with MCC, of whom 1174 received an SLN biopsy. Predictors of SLN positivity were evaluated using logistic regression. Overall survival was evaluated using a Cox proportional hazards model. RESULTS: Of patients who underwent SLN biopsy, those with primary lesions on the trunk (odds ratio, 1.98; 95% confidence interval [CI], 1.23-3.17; P = .004), tumor-infiltrating lymphocytes (odds ratio, 1.58; 95% CI, 1.01-2.46; P = .04), or lymphovascular invasion (odds ratio, 3.45; 95% CI, 2.51-4.76; P < .001) were more likely to have positive SLNs on multivariate analysis. Overall survival was negatively affected by age ≥75 years (hazard ratio [HR], 2.55; 95% CI, 1.36-4.77; P = .003), male sex (HR, 1.78; 95% CI, 1.09-2.91, P = .022), immunosuppression (HR, 3.51; 95% CI, 1.72-7.13; P = .001), and SLN positivity (HR, 3.15; 95% CI, 1.98-5.04; P < .001). LIMITATIONS: Lack of disease-specific survival and potential selection bias from a retrospective data set. CONCLUSIONS: Truncal MCC, tumor-infiltrating lymphocytes, and presence of lymphovascular invasion were independent predictors of positive SLNs. Overall survival was negatively affected by advancing age, male sex, immunosuppression, and SLN positivity.

From randomized clinical trials to real life data. An Italian clinical experience with ixekizumab and its management.

Interleukin(IL)-17 inhibitors display higher efficacy than both TNFi and IL-12/23i, which increased the goal psoriasis area severity index (PASI) from 75 to PASI 90 or even PASI 100. Ixekizumab, a recombinant, humanized IgG4 monoclonal antibody targeting IL-17A displayed a high efficacy and safety in RCTs, namely UNCOVER-2 and UNCOVER-3. However, few studies examined real-life data for these medications, and those which exist highlight discrepancies in efficacy and safety between RCTs and real-life data, likely due to the heterogeneity of patients treated outside of trials. Thus, we performed a single center large prospective observational study (RLSD) that enrolled 47 psoriatic patients followed for 20 weeks and we compared the obtained data with the UNCOVER studies. At week 20 in RLSD versus UNCOVER-3 both PASI-90 and PASI-100 results were similar, whilst at week 12, the RLSD cohort obtained higher PASI 90 (76 vs 69,3%) and PASI-100 (55 vs 39%) than UNCOVER cohorts. Interestingly we also reported higher injection-site related pain that disappeared after week 12. In conclusion, real-life data together with RCTs contribute to enrich the information background available to dermatologists in daily practice.

When IL-17 inhibitors fail: Real-life evidence to switch from secukinumab to adalimumab or ustekinumab.

Psoriasis is a chronic, systemic inflammatory disease that in the moderate to severe forms may benefit of biologics, namely TNF and IL-12/23 and IL-17 inhibitors. Loss of response, lack of response, or discontinuation due to adverse events represent a concrete therapeutic challenge for dermatologists that have to switch patients to other treatments. Although some evidences already exist toward the switch from IL-12/23 and TNF inhibitors to IL-17 inhibitors, conversely nothing is present toward the switch from IL-17 inhibitors to IL-12/23 and TNF inhibitors. We performed a real-life study enrolling 50 patients randomly switched to adalimuamb, a TNF inhibitor, or ustekinumab, an IL-12/23 inhibitor. Our observational study suggests that switching from IL-17i to TNFi and IL-12/23i is a safe and effective therapeutic strategy.

Sex-specific differences in the efficacy of traditional low frequency versus high frequency spinal cord stimulation for chronic pain.

INTRODUCTION: Spinal cord stimulation (SCS), an FDA-approved therapy for chronic pain, uses paresthesia (low frequency SCS (LF-SCS)) or paresthesia-free (such as high-frequency SCS (HF-SCS)) systems, providing analgesia through partially-elucidated mechanisms, with recent studies indicating a sexual dimorphism in pain pathogenesis (Bretherton et al., Neuromodulation, 2021; Paller et al., Pain Med 10:289-299, 2009; Slyer et al., Neuromodulation, 2019; Van Buyten et al., Neuromodulation 20:642-649, 2017; Mekhail et al., Pain Pract, 2021). We aim to evaluate SCS therapy sex effects based on paradigm, utilizing visual analog scores (VAS), perceived pain reduction (PPR), and opioid use. METHODS: A retrospective cohort study of SCS patients implanted between 2004 and 2020 (n = 237) was conducted. Descriptive statistics and linear mixed methods analyses were used. RESULTS: HF-SCS (10 kHz) was implanted in 94 patients (40 females, 54 males), and LF-SCS in 143 (70 females, 73 males). At 3 months and 6 months, HF-SCS (p < 0.001) and LF-SCS (p < 0.005) had lower VAS scores compared to baseline (p < 0.005), with no differences across groups. PPR improved in both post-implantation (p < 0.006) and at 3 months (p < 0.004 respectively), compared to baseline persisting to 6 (p < 0.003) and 12 months (p < 0.01) for HF-SCS, with significantly better PPR for HF-SCS at 3 (p < 0.008) and 6 (p < 0.001) months compared to LF-SCS. There were no differences in opioid use from baseline for either modality; however LF-SCS patients used more opioids at every time point (p < 0.05) compared to HF-SCS. VAS was improved for all modalities in both sexes at 3 months (p = 0.001), which persisted to 6 months (p < 0.05) for HF-SCS males and females, and LF-SCS females. Female HF-SCS had improved PPR at 3 (p = 0.016) and 6 (p = 0.022) months compared to baseline, and at 6 (p = 0.004) months compared to LF-SCS. Male HF-SCS and LF-SCS had improved PPR post-implantation (p < 0.05) and at 3 months (p < 0.05), with HF-SCS having greater benefit at 3 (p < 0.05) and 6 (p < 0.05) months. LF-SCS males but not females used less opioids at 6 months (p = 0.017) compared to baseline; however this effect did not persist. On linear mixed model analyses, including age, sex and stimulator type, VAS decreased with age, at each timepoint, and had a trend towards increasing with female sex, while PPR increased at 3 and 6 months and lastly HF-SCS was associated with decreased opioid use. DISCUSSION: PPR at 3 and 6 months improved to a greater extent in HF-SCS. HF-SCS females had improved PPR at 3 and 6 months, and only LF-SCS males used less opioids at 6 months, potentially indicating sex-based pathway. Future studies should further elucidate differences in sex-based pathways and identify optimal SCS opioid-sparing paradigms for chronic pain patients.

The Association of Frontal Alopecia with a History of Facial and Scalp Surgical Procedures.

INTRODUCTION: The prevalence of frontal fibrosing alopecia (FFA) is increasing worldwide, though the pathogenesis remains unknown. Anecdotal reports describe alopecia occurring in an FFA pattern following facial surgical procedures, but this potential link remains unexplored. OBJECTIVE: The objective of this study is to determine if a significant association exists between the diagnosis of FFA and a history of facial and scalp surgical procedures. METHODS: This retrospective study comparing data from frontal alopecia patients to controls was conducted at a tertiary medical center. Additionally, a literature review was conducted on scarring alopecias occurring from scalp procedures. RESULTS: Fifty percent of frontal alopecia patients (n = 54) reported a history of facial surgical procedures compared to 9.8% of controls (n = 51) (OR: 7.8 [95% CI: 2.77-25.98, p < 0.001]). Although no significant differences were observed in current daily facial sunscreen use, sunscreen use prior to alopecia onset was significantly higher in frontal alopecia (p = 0.295; p = 0.021). Sunscreen use was not a significant modifier in the association between frontal alopecia and facial surgical procedures (p = 0.89). CONCLUSIONS: A significant association exists between frontal alopecia clinically consistent with FFA and a history of facial surgery, the nature of which is unclear. The role of sunscreen use and frontal alopecia development in this setting needs to be better elucidated.