Direct Measurement of Energy Transfer in Strongly Driven Rotating Turbulence.

A short, abrupt increase in energy injection rate into steady strongly driven rotating turbulent flow is used as a probe for energy transfer in the system. The injected excessive energy is localized in time and space and its spectra differ from those of the steady turbulent flow. This allows measuring energy transfer rates, in three different domains: In real space, the injected energy propagates within the turbulent field, as a wave packet of inertial waves. In the frequency domain, energy is transferred nonlocally to the low, quasigeostrophic modes. In wave number space, energy locally cascades toward small wave numbers, in a rate that is consistent with two-dimensional (2D) turbulence models. Surprisingly however, the inverse cascade of energy is mediated by inertial waves that propagate within the flow with small, but nonvanishing frequency. Our observations differ from measurements and theoretical predictions of weakly driven turbulence. Yet, they show that in strongly driven rotating turbulence, inertial waves play an important role in energy transfer, even in the vicinity of the 2D manifold.

Mechanical design principles in frustrated thin elastic sheets.

Using a geometric formalism of elasticity theory we develop a systematic theoretical framework for shaping and manipulating the energy landscape of slender solids, and consequently their mechanical response to external perturbations. We formally express global mechanical properties associated with non-Euclidean thin sheets in terms of their local rest lengths and rest curvatures, and we interpret the expressions as both forward and inverse problems for designing the desired mechanical properties. We show that by wisely designing geometric frustration, anomalous mechanical properties can be encoded into a material using accessible experimental techniques. To test the methodology we derive a family of ribbon-springs with extreme mechanical behavior such as tunable, anharmonic, and even vanishing rigidities. The presented formalism can be discretized, offering a new methodology for designing mechanical properties and thus opens a new pathway for the design of both continuum and discrete solids and structures.

Peri-operative individually tailored psychological intervention in breast cancer patients improves psychological indices and molecular biomarkers of metastasis in excised tumors.

Perioperative stress and inflammatory signaling can invigorate pro-metastatic molecular processes in patients' tumors, potentially worsening long-term survival. Yet, it is unknown whether pre-operative psychotherapeutic interventions can attenuate such effects. Herein, three weeks before surgery, forty women diagnosed with stage I-III invasive ductal/lobular breast carcinoma were randomized to a 6-week one-on-one psychological intervention (6 meetings with a medical psychologist and bi-weekly phone calls) versus standard nursing-staff-attention. The intervention protocol was individually tailored based on evaluation of patients' emotional, cognitive, physiological, and behavioral stress response-patterns, and also included psychoeducation regarding medical treatments and recruitment of social support. Resected primary tumors were subjected to whole-genome RNA sequencing and bioinformatic analyses, assessing a priori hypothesized cancer-relevant molecular signatures. Self-report questionnaires (BSI-18, Hope-18, MSPSS, and a stress-scale) were collected three (T1) and one (T2) week before surgery, a day before (T3) and after (T4) surgery, and three weeks (T5) and 3-months (T6) following surgery. The intervention reduced distress (GSI), depression, and somatization scores (BSI-18: p < 0.01, p < 0.05, p < 0.05; T5 vs. T1). Additionally, tumors from treated patients (vs. controls) showed: (i) decreased activity of transcription control pathways involved in adrenergic and glucocorticoid signaling (CREB, GR) (p < 0.001), pro-inflammatory signaling (NFkB) (p < 0.01), and pro-malignant signaling (ETS1, STAT and GATA families) (p < 0.001, p < 0.01, p < 0.005); (ii) increased M1 macrophage polarization (p < 0.05), and CD4+ T cell activity (p < 0.01); and an unexpected increase in epithelial-to-mesenchymal-transition (EMT) signature (p < 0.005). This is the first randomized controlled trial to show beneficial effects of a psychological perioperative intervention on tumor pro-metastatic molecular biomarkers.

CO2 Laser Matricectomy for the Treatment of Pincer Nail Deformity: A Retrospective Cohort Study.

BACKGROUND: Pincer nail deformity (PND) is a common toenail disorder characterized by transverse over-curvature of the nail plate. It can cause severe pain, chronic inflammation, and recurrent infections. Both conservative and surgical treatment options carry different disadvantages of limited efficacy, high recurrence rate, and poor cosmetic outcome. The study aimed to evaluate the safety and effectiveness of carbon dioxide (CO2) laser matricectomy for the treatment of PND. METHODS: The database of the laser unit of a tertiary medical center was retrospectively searched for all patients who were diagnosed with PND in 2016-2022 and treated with lateral and/or medial matricectomy using CO2 laser. Clinical and follow-up data were collected from the medical files.  Results: The cohort included 19 patients (5 male, 14 female) who underwent 25 partial matricectomies during the study period (some patients had more than one diseased nail). All procedures were successful, with no intraoperative or postoperative complications. There was one documented recurrence at 7 months after treatment. CONCLUSION: Partial CO2 laser matricectomy is safe and effective for the treatment of PND. J Drugs Dermatol. 2023;22(11):1099-1102     doi:10.36849/JDD.7574.

Different effects of chronic omeprazole use on osteoporotic fractures rate in the elderly.

AIMS: To investigate the potential association of chronic use of omeprazole with the occurrence of osteoporotic fractures (OF) in community-dwelling elderly subjects. METHODS: The cohort consisted of community-dwelling residents aged >65 years registered with a large health maintenance organization in Israel between January 2002 and December 2016. Data were retrospectively collected from the electronic medical files on demographics, parameters known to be associated with OF, diagnoses of osteoporotic hip, wrist, and vertebral fractures, and chronic use of omeprazole (>11 prescriptions/year). Time to OF/death/end of study was calculated from the beginning of the study (2002). The risk of fractures in the chronic users of omeprazole was analyzed by multivariate Cox proportional hazard regression model. RESULTS: In total, 46 805 subjects were included (41% men), mean age 83.4±6.4 years, of whom 10 272 (21.9%) were chronic users of omeprazole. During 14 years of follow-up, OF were diagnosed in 414 (4.0%) omeprazole users and 1007 (2.8%) omeprazole nonusers (p < 0.001). In a Cox regression model adjusted for age and gender only, chronic use of omeprazole was associated with a 16% excess of OF. However, when parameters known to be associated with OF were entered into the multivariate Cox regression model, chronic use of omeprazole was not found to be an independent risk factor for OF, either overall (adjusted hazard ratio = 0.965, 95% confidence interval 0.86-1.08, P = .55) or specifically, in the ≥85 years age group (adjusted hazard ration = 0.780, 95% confidence interval 0.635-0.958, P < .05) in which an inverse correlation between omeprazole use and OF, was demonstrated. CONCLUSIONS: Chronic use of omeprazole was not associated with the occurrence of OF in elders.

Gastric cancer risk in the elderly is associated with omeprazole use and inversely associated with aspirin use.

BACKGROUND: The association between long-term omeprazole use and gastric cancer (GC) risk is controversial. The aim of this study was to investigate the incidence of GC in elderly community-dwelling omeprazole chronic users with/without aspirin compared to non-users. METHODS: The registry of a large health management organization was searched for all community-dwelling members aged ≥65 years from January 2002 to December 2016. Data on demographics, background parameters, and chronic omeprazole and aspirin use (>11 prescriptions/year) were retrieved. Those diagnosed with new-onset GC during the study period (from January 2003) were identified. RESULTS: Of 51 405 subjects who met the inclusion criteria, 197 were diagnosed with GC during a mean follow-up period of 8.74 ±â€…4.16 years. This group accounted for 0.7% of PPI chronic users (72/11 008) and 0.3% (125/40 397) of nonusers (P < 0.001). GC risk was directly associated with omeprazole chronic use [hazard ratio (HR) 2.03, 95% confidence interval (CI): 1.51-2.73, P < 0.001] and inversely associated with aspirin chronic use (HR 0.55, 95% CI: 0.40-0.75, P < 0.001). Each year of omeprazole use increased GC risk by 9%, and each year of aspirin use decreased GC risk by 10% among omeprazole chronic users. The lowest rate of GC was found in omeprazole nonusers/ aspirin chronic users, and the highest, in omeprazole chronic users/aspirin nonusers. CONCLUSION: Higher GC rate was associated with omeprazole chronic use and inversely associated with aspirin chronic use relative to omeprazole nonuse in community-dwelling elderly.

Laser and light therapy for pediatric hair removal: a systematic review.

Hair removal with lasers and intense pulsed light (IPL) is considered safe. However, data on the efficacy and safety of these procedures specifically in the pediatric population remain sparse. To determine the efficacy and safety of lasers and IPL for hair reduction in children and adolescents, a systematic review was conducted of original studies evaluating hair removal with lasers or IPL in patients aged less than 18 years. Primary outcome measures were efficacy and safety of treatment. The literature review yielded 2 retrospective cohort studies and 11 case reports/case series including a total of 71 patients aged 9 months to 17 years. Diagnoses ranged from localized lumbosacral to generalized hypertrichosis. Six treatment modalities were evaluated: alexandrite, Nd:YAG, Q-switched Nd:YAG, ruby, and diode lasers and IPL. Only one of the cohort studies (n = 28), using the ruby laser, provided efficacy data. The results showed a 63% hair loss in 89% of patients after completion of treatment, although partial regrowth was evident during 6 to 32 weeks of follow-up. Most of the case reports and case series (10/11) reported significant hair reduction following laser and IPL treatments. None of the patients experienced scarring or dyspigmentation. Some kind of pain management was necessary in 65% of patients; 25% required general anesthesia. On the basis of the limited available data which consisted primary of case reports and case series, lasers and IPL might be effective for pediatric hair reduction. Recurrence following treatment may be higher in children than adults, and pain control may be a limiting factor.

Predictors of poor outcome following liver biopsy for the investigation of new hepatic space occupying lesion/s.

BACKGROUND: Ultrasound-guided percutaneous liver biopsy (UPLB) is currently performed mainly to determine if new hepatic space occupying lesions (SOL) represent benign, primary malignant, or metastatic disease. This study sought to investigate the outcome of UPLB in this setting. METHODS: In a retrospective study, patients with a new hepatic SOL who underwent UPLB during 1/2006-12/2016 were included and followed to 12/2018. Clinical data and pathology reports were reviewed. Mortality within 60 days and no change in patients' management following UPLB were defined as medically futile. RESULTS: Included 140 patients, 50% male, mean age 68.8 ± 11.5 years; 112 patients died, all of malignant disease. 32 patients (23%) died within 60 days of UPLB. Median post-UPLB survival was 151 days. Survival was significantly shorter in patients with >1 hepatic lesion (n = 108) or an extrahepatic malignant lesion (n = 77) (p = 0.0082, p = 0.0301, respectively). On Cox Proportional Hazards analysis, significant predictors of mortality within 60 days of UPLB were: age as a continuous variable, (HR 1.070, 95% CI 1.011-1.131, p = 0.018), serum albumin <2.9 g/dL, (HR 4.822 95% CI 1.335-17.425, p = 0.016) and serum LDH >1500 U/L (HR 9.443, 95% CI 3.404-26.197, p < 0.0001). CONCLUSIONS: In patients with these features or with disseminated disease, liver biopsy should be carefully reconsidered.

Rate of breast biopsy referrals in female BRCA mutation carriers aged 50 years or more: a retrospective comparative study and matched analysis.

PURPOSE: To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. METHODS: The study group consisted of 330 women with pathogenic variants (PVs) in BRCA1/2 attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients aged 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended by international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. RESULTS: The total biopsy rate per 1000 follow-up years was 61.7 in the study group and 22.7 in the control group (p < 0.001). The corresponding positive biopsy rates per 1000 follow-up years were 26.4 and 2.0 (p < 0.001), and the positive biopsy percentages, 42.9% and 8.7% (p < 0.0001). CONCLUSION: Women aged 50 + years with PVs in BRCA1/2 attending a dedicated clinic have a 2.7 times higher biopsy rate per 1000 follow-up years, a 13.2 times higher positive biopsy rate per 1000 follow-up years, and a 4.9 times higher positive biopsy percentage than same-aged women in the general population.

Association of Anemia with Dementia and Cognitive Decline among Community-Dwelling Elderly.

INTRODUCTION: The association of anemia with dementia in elders is controversial. We examined the potential association of anemia with dementia in a large population of elders. METHODS: Historical-prospective registry-based study. Included 36,951 community-dwelling elders (65-113 years) that were followed during 2002-2012. Anemia of all kinds was defined according to Clalit Health Services (CHS) definitions: hemoglobin (HGB) <14 g/dL men, <12 g/dL women; and World Health Organization (WHO): HGB <13 g/dL men, <12 g/dL women. Anemia was categorized as mild (HGB 11-13 g/dL men, 11-12 g/dL women) or moderate-severe (HGB <8-10.9 g/dL men and women). Background data, laboratory values, and diagnosis of dementia and cognitive decline (DCD) were reviewed. RESULTS: During the 10-year follow-up period, DCD was newly diagnosed in 7,180 subjects (19.4%). Subjects with DCD had a higher rate of anemia than those without DCD. Time to development of DCD was 1.5 years shorter in those with than without anemia. On multivariate Cox regression analysis adjusted for age and sex, the hazard ratio (HR) for DCD was 1.45 (95% CI: 1.37-1.54) by CHS and 1.51 (95% CI: 1.41-1.61) WHO anemia criteria. The more severe the anemia, the greater the risk of DCD development (HGB 13-14 g/dL [men only], HR = 1.20 [95% CI: 1.09-1.32]; mild anemia, HR = 1.38 [95% CI: 1.28-1.49]; moderate-severe anemia, HR = 1.64 [CI: 1.41-1.90]). Every decrease in 1 standard deviation of HGB (1.4 g/dL) increased the DCD risk by 15%. A competing risk model has weakened the association of anemia with DCD risk. CONCLUSIONS AND IMPLICATIONS: Anemia in community-dwelling elders appears to be associated with an increased DCD risk in a dose-response manner. Application of the WHO anemia criteria in men may miss patients with mild anemia that places them at DCD risk. Further research should look at anemia as a cause of reversible dementia.

Wood Warping Composite by 3D Printing.

Wood warping is a phenomenon known as a deformation in wood that occurs when changes in moisture content cause an unevenly volumetric change due to fiber orientation. Here we present an investigation of wood warped objects that were fabricated by 3D printing. Similar to natural wood warping, water evaporation causes volume decrease of the printed object, but in contrast, the printing pathway pattern and flow rate dictate the direction of the alignment and its intensity, all of which can be predesigned and affect the resulting structure after drying. The fabrication of the objects was performed by an extrusion-based 3D printing technique that enables the deposition of water-based inks into 3D objects. The printing ink was composed of 100% wood-based materials, wood flour, and plant-extracted natural binders cellulose nanocrystals, and xyloglucan, without the need for any additional synthetic resins. Two archetypal structures were printed: cylindrical structure and helices. In the former, we identified a new length scale that gauges the effect of gravity on the shape. In the latter, the structure exhibited a shape transition analogous to the opening of a seedpod, quantitatively reproducing theoretical predictions. Together, by carefully tuning the flow rate and printing pathway, the morphology of the fully dried wooden objects can be controlled. Hence, it is possible to design the printing of wet objects that will form different final 3D structures.

[DIFFERENT APPROACHES TO MAMMOGRAPHY AS A SCREENING TOOL FOR BREAST CANCER].

INTRODUCTION: Mammography as a screening tool can reduce mortality from breast cancer. Nevertheless, it has disadvantages such as false positive results, false negative, impaired sensitivity in women with dense breast over-diagnosis and radiation. Due to the different weight given to the advantages versus the disadvantages of mammography, different approaches to screening have developed. These range from annual screening starting at the age of 40 years, to biannual screening starting at the age of 50. The official screening program in Israel is biannual screening between the ages of 50 and 74.

Chronic omeprazole use in the elderly is associated with decreased risk of dementia and cognitive decline.

BACKGROUND: The association between proton pump inhibitor (PPI) use and increased risk of dementia is controversial. AIM: Investigating this issue in a large population of community-dwelling elders. METHODS: Our database was retrospectively searched for all community-dwelling patients aged ≥65 years who newly diagnosed with dementia/cognitive decline (DCD) between January 2002 - December 2012. Receiving ≥11 prescriptions of PPIs/year was categorized as PPI users. Clinical data were collected from the medical files. Risk of DCD in PPI users was analyzed by Cox regression models. RESULTS: Included 48,632 elders of whom 8,848 were diagnosed with DCD (18.2%). PPI use was documented in 10,507, of whom 1,959 were subsequently diagnosed with DCD (18.6%). Among 38,125 non-PPI users, 6,889 (18.1%) were diagnosed with DCD. The hazard ratio for occurrence of DCD in PPI users compared to non-users was 0.85 (95% CI: 0.81-0.89, P <0.001) in an un-adjusted Cox regression model and 0.83 in a Cox regression model adjusted for age and sex (95% CI: 0.79-0.87, P <0.001). Multivariate Cox regression accounting for background diseases, marital status, and socioeconomic state yielded a hazard ratio of 0.77 (95% CI: 0.73-0.81, P <0.001). CONCLUSION: PPI use wasn't associated with DCD development in chronic PPI users.

Shaping by Internal Material Frustration: Shifting to Architectural Scale.

Self-morphing of thin plates could greatly impact the life if used in architectural context. Yet, so far, its realizations are limited to small-scale structures made of model materials. Here, new fabrication techniques are developed that turn two conventional construction materials-clay and fiber composites (FRP)-into smart, self-morphing materials, compatible with architectural needs. Controlled experiments verify the quantitative connection between the prescribed small-scale material structure and the global 3D surface, as predicted by the theory of incompatible elastic sheets. Scaling up of desired structures is demonstrated, including a method that copes with self-weight effects. Finally, a method for the construction of FRP surfaces with complex curvature distribution is presented, together with a software interface that allows the computation of the 3D surface for a given fiber pattern (the forward problem), as well as the fiber distribution required for a desired 3D shape (the inverse problem). This work shows the feasibility of large-scale self-morphing surfaces for architecture.

Buckling-Fracture Transition and the Geometrical Charge of a Crack.

We present a unifying approach that describes both surface bending and fracture in the same geometrical framework. An immediate outcome of this view is a prediction for a new mechanical transition: the buckling-fracture transition. Using responsive gel strips that are subjected to nonuniform osmotic stress, we show the existence of the transition: Thin plates do not fracture. Instead, they release energy via buckling, even at strains that can be orders of magnitude larger than the Griffith fracture criterion. The analysis of the system reveals the dependence of the transition on system's parameters and agrees well with experimental results. Finally, we suggest a new description of a mode I crack as a line distribution of Gaussian curvature. It is thus exchangeable with extrinsic generation of curvature via buckling. The work opens the way for the study of mechanical problems within a single nonlinear framework. It suggests that fracture driven by internal stresses can be completely avoided by a proper geometrical design.

A novel role for an old target: CD45 for breast cancer immunotherapy.

Breast cancer subtypes have not shown significant response to current immunomodulatory therapies. Although most subtypes are treatable, triple negative breast cancer (TNBC), an aggressive highly metastatic cancer, comprising 10-20% of breast cancers, remains an unmet medical need. New strategies are needed in order to overcome flaws in the responsiveness to current TNBC therapies. Our aims were: first, to determine the efficacy of a novel immunomodulatory peptide, C24D, on TNBC and second, to elucidate the molecular mechanism by which C24D induces immune-modulating tumor killing. Using mass spectrometry analysis, we identified CD45 as the C24D binding receptor. In vitro and in vivo TNBC models were used to assess the efficacy of C24D in reversing TNBC-induced immunosuppression and in triggering immune-modulated tumor cell killing. The CD45 signal transduction pathway was evaluated by western blot and FACS analyses. We revealed that addition of PBMCs from healthy female donors to TNBC cells results in a cascade of suppressive CD45 intracellular signals. On binding to CD45's extra-cellular domain on TNBC-suppressed leukocytes, the C24D peptide re-activates the Src family of tyrosine kinases, resulting in specific tumor immune response. In vitro, immune reactivation by C24D results in an increase of CD69+ T and CD69+ NK cells, triggering specific killing of TNBC cells. In vivo, C24D induced CD8+ and activated CD56+ tumor infiltrated cells, resulting in tumor apoptosis. Our results should renew interest in molecules targeting CD45, such as the C24D peptide, as a novel strategy for TNBC immunotherapy.

Packing of stiff rods on ellipsoids: Geometry.

We suggest a geometrical mechanism for the ordering of slender filaments inside nonisotropic containers, using cortical microtubules in plant cells and the packing of viral genetic material inside capsids as concrete examples. We show analytically how the shape of the cell affects the ordering of phantom elastic rods that are not self-avoiding (i.e., self-crossing is allowed). We find that for oblate cells, the preferred orientation is along the equator, while for prolate spheroids with an aspect ratio close to 1, the orientation is along the principal (long axis). Surprisingly, at a high enough aspect ratio, a configurational phase transition occurs and the rods no longer point along the principal axis, but at an angle to it, due to high curvature at the poles. We discuss some of the possible effects of self-avoidance using energy considerations. These results are relevant to other packing problems as well, such as the spooling of filament in the industry or spider silk inside water droplets.

A combination of 1064 nm Q-switched fractional ND-YAG laser with a nonfractional microsecond pulsed technology has a synergistic effect for nonablative facial rejuvenation.

BACKGROUND: Non-ablative fractionated lasers for facial rejuvenation are increasingly preferred over ablative lasers due to their minimal downtime and fewer adverse events. The synergistic effect of the Q-switched fractional (QSF) 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, in combination with the non-fractional microsecond pulsed technology has yet to be fully evaluated. AIM: Our objective was to determine the safety and efficacy of this combination treatment for skin rejuvenation. METHODS: Patients who underwent treatment using the QSF-Nd:YAG laser, followed by the non-fractional microsecond pulsed Nd:YAG were evaluated retrospectively using a novel 3D imaging modality for degree of facial erythema, wrinkles surface area, and wrinkle depth. Pain perception, adverse effects, and patient satisfaction were assessed at the 2-month post-treatment follow-up visit, graded on a scale of 1- 5 (1 = not satisfied, 5 = very satisfied). RESULTS: Ten female patients' ages 44-67 (mean 55 years) completed both treatment and follow-up period, with an overall mild improvement in facial erythema and wrinkle surface area (mean improvement of 18% and 19.5% accordingly), as well as a mild improvement in overall wrinkle depth. Pain and adverse effects were mild and transient. Patients' satisfaction was high. CONCLUSION: The combination of the QSF-Nd:YAG laser and non-fractional microsecond pulsed technology, using a single Nd:YAG 1064 nm laser platform, was found safe and effective as a non-ablative modality for facial rejuvenation, as demonstrated by a novel 3D imaging modality.

Laser Treatment for Non-Melanoma Skin Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgery is the mainstay of treatment for non-melanoma skin cancer. Lasers are an additional option. OBJECTIVE: The objective of this study was to review the literature on the efficacy and safety of lasers for the treatment of non-melanoma skin cancer. METHODS: A systematic review and meta-analysis of laser treatment for non-melanoma skin cancer was performed. The primary outcome was recurrence rate (RR). RESULTS: The review included 32 studies (six randomized controlled trials and 26 cohort studies): 27 evaluated basal cell carcinomas (BCCs), three squamous cell carcinomas, and two both, for a total of 4755 BCCs and 214 squamous cell carcinoas. Most BCCs were low risk. The Nd:YAG laser (seven studies, 3286 BCCs) had a 3.1% RR (95% confidence interval [CI] 1.4-6.4%) during a mean follow-up of 7.9 years, with a low rate (< 20%) of scarring and dyspigmentation. The CO2 laser (ten studies, 904 BCCs) had a 9.4% RR (95% CI 4.1-20) during a mean follow-up of 2.1 years, with a low rate of side effects. The pulsed dye laser (eight studies, 206 BCCs) had a 38% RR (95% CI 24-55). In two studies, the Nd:YAG laser demonstrated a RR of 10% (95% CI 2-31) for Bowen's disease, and in three studies, the CO2 laser demonstrated a RR of 22% (95% CI 5-61) for squamous cell carcinoma. CONCLUSIONS: Based on cohort studies, the Nd:YAG laser is a safe and efficacious modality for the treatment of low-risk BCC. Based on settings applied in prior studies in the literature, the CO2 laser is less efficacious than the Nd:YAG laser, thus it cannot be recommended for BCC treatment. Insufficient data preclude conclusions regarding laser treatment for squamous cell carcinoma. REGISTRATION: PROSPERO registration number CRD42019129717.

Treatment of Bullous Pemphigoid in People Aged 80 Years and Older: A Systematic Review of the Literature.

BACKGROUND: Bullous pemphigoid commonly affects older adults and has a detrimental effect on both quality of life and longevity. Systemic corticosteroids, the mainstay of therapy, may cause significant adverse effects, especially in older patients. Therefore, safer therapeutic options are being sought. OBJECTIVE: The objective of this article was to systematically review the published evidence on the efficacy and safety of different treatment modalities for bullous pemphigoid in older patients. METHODS: We performed a systematic review of all publications until May 2020 in PubMed, Google Scholar, and the ongoing trials registry of the US National Institutes of Health databases evaluating the efficacy and safety of bullous pemphigoid treatments in patients aged older than 80 years. The primary outcome was complete response. The secondary outcomes were partial response, complete remission on minimal therapy or during tapering, recurrence, adverse events, and mortality. RESULTS: Twenty-eight publications were included: 2 randomized controlled trials, 5 prospective cohort studies, 10 retrospective cohort studies, and 11 case series, with a total of 153 older patients. The overall complete response rate was 31%. Topical corticosteroids had the highest complete response rate (55%) with a low side-effect profile. Biologics (omalizumab and rituximab) were effective in achieving complete remission on minimal therapy (29%) without recurrence, although rituximab was associated with a relatively high mortality rate (29%). CONCLUSIONS: Current data suggest that topical corticosteroids are effective and safe and should remain the first line of treatment for bullous pemphigoid in older adults. However, their application is difficult and requires a high-functioning patient, third-party assistance, or a relatively mild disease. Biological agents are effective but warrant meticulous patient selection owing to the relatively high mortality rate associated with rituximab. CLINICAL TRIAL REGISTRATION: PROSPERO registration number CRD42020186686.