Counterfactual Sepsis Outcome Prediction Under Dynamic and Time-Varying Treatment Regimes.

Sepsis is a life-threatening condition that occurs when the body's normal response to an infection is out of balance. A key part of managing sepsis involves the administration of intravenous fluids and vasopressors. In this work, we explore the application of G-Net, a deep sequential modeling framework for g-computation, to predict outcomes under counterfactual fluid treatment strategies in a real-world cohort of sepsis patients. Utilizing observational data collected from the intensive care unit (ICU), we evaluate the performance of multiple deep learning implementations of G-Net and compare their predictive performance with linear models in forecasting patient outcomes and trajectories over time under the observational treatment regime. We then demonstrate that G-Net can generate counterfactual prediction of covariate trajectories that align with clinical expectations across various fluid limiting regimes. Our study demonstrates the potential clinical utility of G-Net in predicting counterfactual treatment outcomes, aiding clinicians in informed decision-making for sepsis patients in the ICU.

Prolonged Opioid Use Is Associated With Poor Pain Alleviation After Orthopaedic Surgery.

INTRODUCTION: Severe pain after orthopaedic surgery is common and often results in chronic postsurgical pain and chronic opioid use (COU). Poor pain alleviation (PPA) after surgery is a well-described modifiable risk factor of COU. Although PPA's role in inducing COU is recognized in other areas, it is not well defined in orthopaedic surgery. The aim of this study was to evaluate the influence of PPA on COU in the population who underwent orthopaedic surgery. METHODS: Medical records from a large academic medical center from 2015 to 2018 were available for analysis. Patients undergoing nononcologic surgical procedures by the orthopaedic surgery service that also required at least 24 hours of hospital stay for pain control were included in the study. Surgery type, body location, basic demographics, preoperative opioid use, comorbidities, medications administered in the hospital, opioid prescription after discharge, and length of stay were recorded. COU was defined as a continued opioid prescription at ≥ 3 months, ≥ 6 months, or ≥ 9 months after surgery. PPA was defined as having a recorded pain score of eight or more, between 4 and 12 hours apart, three times during the hospital stay. RESULTS: A total of 7,001 patients were identified. The overall rate of COU was 25.3% at 3 months after surgery. Charlson Comorbidity Index > 0 and PPA were statistically significant predictors of opioid use at all time points. Preoperative opioid naivety was associated with decreased COU. The type and location of surgical procedures were not associated with COU, after controlling for baseline variables. CONCLUSION: Our findings demonstrated an overall high rate of COU. The known risk factors of COU were evident in our study population, particularly the modifiable risk factor of acute postsurgical PPA. Better management of postsurgical pain in orthopaedic patients may lead to a decrease in the rates of COU in this group.

Titration of Ventilator Settings to Target Driving Pressure and Mechanical Power.

PURPOSE: Driving pressure (ΔP) and mechanical power (MP) may be important mediators of lung injury in acute respiratory distress syndrome (ARDS) however there is little evidence for strategies directed at lowering these parameters. We applied predictive modeling to estimate the effects of modifying ventilator parameters on ΔP and MP. METHODS: 2,622 ARDS patients (Berlin criteria) from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version1.0) admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center between 2008 and 2019 were included. Flexible confounding-adjusted regression models for time varying data were fit to estimate the effects of adjusting PEEP and tidal volume (VT) on ΔP, and adjusting VT and respiratory rate (f) on MP. RESULTS: Reduction in VT reduced ΔP and MP, with more pronounced effect on MP with lower compliance. Strategies reducing f, consistently increased MP (when VT was adjusted to maintain consistent minute ventilation). Adjustment of PEEP yielded a U-shaped effect on ΔP. CONCLUSIONS: This novel conditional modeling confirmed expected response patterns for ΔP, with the response to adjustments depending on patients' lung mechanics. Furthermore a VT -driven approach should be favored over a f -driven approach when aiming to reduce MP.

Mycosis fungoides with epidermal mucinosis: a variant of mycosis fungoides with a spongiosis-like pattern.

BACKGROUND: The histopathologic diagnosis of mycosis fungoides (MF) has classically relied on the presence of atypical epidermotropic T-lymphocytes predominating over spongiosis. However, in some cases of MF, prominent epidermal mucinosis in a spongiosis-like pattern mimics a spongiotic dermatitis. To our knowledge, only one series in the literature has thus far recognized the presence of epidermal mucinosis in MF. METHODS: We evaluated 30 skin biopsies from 18 patients with the clinical diagnosis of MF, which fulfilled all histopathologic criteria for patch- or plaque-stage MF, but also showed epidermal mucinosis in a spongiosis-like pattern. A total of 15 specimens were studied by immunohistochemistry, and seven were tested for T-cell receptor (TCR) gene rearrangements. Twenty biopsies of spongiotic dermatitides were included as controls. RESULTS: We confirmed the presence of epidermal mucinosis in all 30 cases of MF with a spongiosis-like pattern based on histopathologic criteria and the colloidal iron stain for mucin. Immunohistochemistry in 15 specimens showed significant loss of pan-T-cell antigens CD5 (10/15) and CD7 (14/15); and TCR clonality was detected in 7 specimens from 6 patients, supporting the diagnosis of MF. CONCLUSIONS: We report helpful histopathologic criteria for distinguishing MF with epidermal mucinosis in a spongiosis-like pattern from spongiotic dermatitis.

Co-occurrence of Kikuchi-Fujimoto's disease and Still's disease: case report and review of previously reported cases.

Kikuchi-Fujimoto's disease (KFD) and adult-onset Still's disease (AOSD) are rare inflammatory conditions with some overlapping features. We encountered a 22-year-old male patient who presented with daily fevers, neck discomfort, and sore throat and subsequently developed rash, arthritis, and cervical lymphadenopathy. Biopsy of the skin rash was consistent with KFD skin involvement. Given that the patient also met criteria for AOSD, a final diagnosis of KFD/AOSD co-occurrence was made. Anti-IL-1ß therapy with anakinra resulted in rapid resolution of all symptoms. A literature search identified eight more cases of KFD/AOSD. Fever, rash, arthritis, and lymphadenopathy were present in all patients. No case report demonstrated an association of rash eruption clearly associated with fever spikes. Duration of symptoms ranged from 3 weeks to 10 years. Seven patients had leukocytosis, six had anemia, and five demonstrated elevated ferritin and/or decreased glycosylated ferritin. Seven patients had elevated erythrocyte sedimentation rate (ESR), and seven had transaminitis. Eight of nine patients had no evidence of infectious disease. Autoantibodies were absent from all patients. KFD and AOSD are very rare diseases, yet they may overlap. The two conditions not only share several clinical and laboratory characteristics but also differ in characteristic ways. Given the rapid response observed with anakinra in the index patient, IL-1ß likely plays a role in both diseases.

Primary cutaneous follicle-center lymphoma.

We present a 64-year-old man with a three-year history of pruritic, pink papules and nodules of the face who was found to have a clonal lymphoproliferative B-cell disease that was characterized by a clonal IGH rearrangement. Although morphologic features present in the biopsy specimen were consistent with a reactive process, additional clinicopathologic correlation (anatomic presentation of lesions on the face, the absence of t(14:18) translocation, and bcl-2 and MUM1 expression) reinforced suspicion of a cutaneous B-cell lymphoma. Systemic work-up with CT/PET and a bone marrow biopsy ultimately excluded systemic disease and primary cutaneous follicle-center lymphoma (PCFCL) was a strong diagnostic consideration. The patient was treated with systemic rituximab with a partial resolution of the facial lesions. The case demonstrates both clinical and pathologic challenges to the diagnosis of primary cutaneous B-cell lymphoma (PCBCL). Furthermore, despite a newly refined classification system, the case also specifically highlights the persistent requirement for flexible clinical reasoning and pathologic correlation. Such reasoning is necessary to generate individualized strategies for diagnosis and treatment when cutaneous B-cell lymphoma is suspected.

Cranial fasciitis.

A 26-year-old man presented with an 18-month history of a subcutaneous mass on his forehead that occurred shortly after being struck by a blunt object. Histopathologic examination showed a proliferation of bland spindle cells and a collagenous stroma that was consistent with cranial fasciitis. Cranial fasciitis, which is a variant of nodular fasciitis, is a benign fibroblastic neoplasm that overlies the skull and often is associated with trauma. Although its rapid onset may give the clinical impression of a malignant condition, cranial fasciitis typically is cured by simple excision without further sequelae.

Candida parapsilosis of the nail-bed without onychomycosis.

Candida parapsilosis is an emerging fungal pathogen that was once thought to be solely a colonizing organism. C. parapsilosis is increasingly becoming reported as the most common Candida species that causes onychomycosis. Clinical findings include typically severe dystrophy of the nail fold and plate as well as thickening and fragmentation of the plate, particularly in the distal plate. We present a unique case of C. parapsilosis infection of the nail bed without infection of the nail plate and with twenty-nail melanonychia.

Trauma-related papular granuloma annular.

Granuloma annulare (GA) is a benign, granulomatous disease with several clinical manifestations, which include localized, generalized, perforating, subcutaneous, patch, papular, and linear forms. We report a case of papular GA of the dorsal aspects of the hands that arose after repeated, direct trauma to the site of subsequent involvement. Although multiple etiologies for GA have been proposed, which include ultraviolet light, arthropod bites, trauma, tuberculin skin tests, viral infections, and PUVA photochemotherapy, the underlying pathogenesis of the disorder remains unclear. However, owing to the key histopathologic findings of focal collagen and elastic fiber degeneration and mucin deosition in GA, it is not surprising that cutaneous trauma may have played a role in connective tissue injury, subsequent degeneration, and the production of a granulomatous response with increased mucin deposition.

Minocycline-induced hyperpigmentation in multibacillary leprosy.

Minocycline has been used in the treatment of leprosy since the demonstration of its efficacy in inhibiting Mycobacterium leprae growth in 1987. Hyperpigmentation, a well-documented adverse effect, classically shows 3 clinical and histological patterns: type I consists of blue-black pigmentation in areas of current or previous inflammation, type II consists of blue-gray pigmentation of normal skin, often seen on the legs, and type III consists of diffuse muddy-brown pigmentation accentuated on sun-exposed sites. Whereas type I hyperpigmentation stains positively for hemosiderin and type III hyperpigmentation stains positively for melanin, type II hyperpigmentation stains positively for both. We describe 2 patients with leprosy on minocycline therapy who developed multiple patches of blue-gray pigmentation within preexisting leprosy lesions. Biopsies from both patients demonstrated deposition of brownish-black pigment granules within the cytoplasm of foamy histiocytes that was highlighted by both Perls and Fontana-Masson stains. Given the clinical and histological findings in our patients, it is as yet unclear whether this coexistent type I clinical pattern and type II histopathologic pattern of pigmentation is unique to multibacillary leprosy. These findings provide support for the existence of additional subtypes of minocycline-induced hyperpigmentation that do not adhere to the classic 3-type model described.

Patient follow-up after participating in a beach-based skin cancer screening program.

Many skin cancer screenings occur in non-traditional community settings, with the beach being an important setting due to beachgoers being at high risk for skin cancer. This study is a secondary analysis of data from a randomized trial of a skin cancer intervention in which participants (n = 312) had a full-body skin examination by a clinician and received a presumptive diagnosis (abnormal finding, no abnormal finding). Participants' pursuit of follow-up was assessed post-intervention (n = 283). Analyses examined: (1) participant's recall of screening results; and (2) whether cognitive and behavioral variables were associated with follow-up being as advised. Just 12% of participants (36/312) did not correctly recall the results of their skin examination. One-third (33%, 93/283) of participants' follow-up was classified as being not as advised (recommend follow-up not pursued, unadvised follow-up pursued). Among participants whose follow-up was not as advised, 71% (66/93) did not seek recommended care. None of the measured behavioral and cognitive variables were significantly associated with recall of screening examination results or whether follow-up was as advised. Research is needed to determine what factors are associated with follow-up being as advised and to develop messages that increase receipt of advised follow-up care.

Chronic cutaneous graft-versus-host disease simulating hypertrophic lupus erythematosus--a case report of a new morphologic variant of graft-versus-host disease.

The spectrum of clinical and histopathologic features associated with chronic graft-versus-host disease (GVHD) is broad, with recognized variants simulating scleroderma, lichen sclerosus, eosinophilic fasciitis, and de novo diffuse melanoderma. We report a case of a patient with multiple myeloma who presented approximately 1 year after his allogeneic hematopoietic stem cell transplantation with lesions of chronic lichenoid GVHD that harbored features of hypertrophic lupus erythematosus (LE) and that was initially mistaken for a superficial well-differentiated squamous cell carcinoma (SCC). However, in 4 years of follow-up, the patient failed to develop any evidence of cutaneous or systemic LE, actinic damage, or SCC, and the lesions cleared with topical and systemic treatments appropriate for chronic GVHD. For proper interpretation of the histologic findings of GVHD, it is important for the dermatopathologist to be aware of unusual manifestations. Knowledge of the occurrence of hypertrophic LE and familiarity with its histologic features is also important to avoid an erroneous diagnosis of SCC in immunosuppressed patients.

Morbihan disease.

Morbihan disease, which consists of solid facial edema, is a rare complication of rosacea, a common cutaneous disorder in middle-aged individuals. The characteristic features of Morbihan disease are its chronic course, typical clinical picture, lack of specific laboratory and histopathologic findings, and refractoriness to therapeutic measures. Since its initial description in 1957, only a small number of cases have been reported in the dermatologic literature. We report a 54-year-old man who developed a two-year duration of erythema and edema that affects the upper and mid face, with accentuation in the periorbital region. Patch tests excluded an allergic contact dermatitis and histopathologic investigation showed small, nodular clusters of epithelioid cells in the dermis that were consistent with sarcoidal granulomata. A diagnosis of Morbihan disease was made owing to the combination of clinical and histopathologic findings. Therapeutic options for the disease remain unsatisfactory and treatments reported in the literature include systemic glucocorticoids, oral tetracyclines, thalidomide, isotretinoin, ketotifen, and clofazimine. Our patient failed a six-to-seven months course of minocycline prior to presentation and has since experienced improvement on gradually-increasing doses of isotretinoin.

Acquired brachial cutaneous dyschromatosis.

Acquired brachial cutaneous dyschromatosis (ABCD) is a newly described disorder of pigmentary change that occurs on the dorsal aspects of the forearms in post-menopausal women. We report a case of a 62-year-old woman who developed an asymptomatic, reticulated, gray-brown eruption on the dorsal aspects of the forearms of gradual onset that is clinically and histopathologically consistent with ABCD. Whereas the original report found an association between hypertension and/or the use of anti-hypertensive medications in the original cohort, we propose that this entity may, in fact, be associated more closely with cumulative sun damage and may be related to such acquired disorders of the skin as poikiloderma of Civatte. Treatment of these lesions may prove to be a challenge, with an emphasis on rigorous sun protection and adjunctive measures with depigmentating agents, chemical peels, and lasers.

Acute graft-versus-host disease following hematopoietic stem-cell transplantation.

Hematopoietic stem-cell transplantation has become the standard of care for numerous malignant and nonmalignant conditions. As the number of stem-cell transplants performed worldwide rises, it is imperative that dermatologists taking care of these patients are able to understand the methods of transplantation, as well as to recognize and treat the cutaneous complications that commonly follow transplant, particularly acute graft-versus-host disease.

Skin cancer education and early detection at the beach: a randomized trial of dermatologist examination and biometric feedback.

BACKGROUND: There are limited data on the effectiveness of skin cancer prevention education and early detection programs at beaches. OBJECTIVES: We evaluate 4 strategies for addressing skin cancer prevention in beach settings. METHODS: This prospective study at 4 beaches included 4 intervention conditions: (1) education only; (2) education plus biometric feedback; (3) education plus dermatologist skin examination; or (4) education plus biometric feedback and dermatologist skin examination. Outcomes included sun protection behaviors, sunburns, and skin self-examinations. RESULTS: There was a significant increase in hat wearing, sunscreen use, and a reduction in sunburns in the education plus biometric feedback group (odds ratio = 1.97, 1.94, and 1.07, respectively), and greater improvements in knowing what to look for in skin-self examinations (odds ratio = 1.13); there were no differences in frequency of self-examinations. Skin examinations plus biometric feedback led to greater reductions in sunburns. The dermatologist examinations identified atypical moles in 28% of participants. LIMITATIONS: Inclusion of only one beach per condition, use of self-report data, and a limited intervention period are limitations. CONCLUSIONS: Education and biometric feedback may be more effective than education alone for impacting sun protective attitudes and behaviors in beachgoing, high-risk populations.

Pityriasis versicolor: a systematic review of interventions.

OBJECTIVE: To determine the efficacy of topical or systemic agents in the treatment and prevention of pityriasis versicolor. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The Cochrane Skin Group Specialized Register (to June 2008), Cochrane Central Register of Controlled Trials, MEDLINE (1950 to June 2008), EMBASE (1974 to June 2008), LILACS (to March 2009), the gray literature, and sources for registered trials to November 2008. Reference lists of all retrieved trials and review articles were checked for additional trials. STUDY SELECTION: Controlled trials that examined therapies used in children or adults with a clinical or microscopic diagnosis of pityriasis versicolor. DATA EXTRACTION: The primary outcome measure included a negative result from mycological evaluation of participants with direct microscopy using potassium hydroxide smear. The secondary outcome measures were findings from Wood's light examination and a negative clinical evaluation result, with disappearance of visual signs (except pigmentary defects) and symptoms. DATA SYNTHESIS: Results of treatment and prevention of pityriasis versicolor infection in 8327 participants in 93 controlled trials were examined. Overall, trials investigating the efficacy of therapeutic and prophylactic treatments for pityriasis versicolor are poorly reported and may be of low quality. Most trials did not adequately report the methods of randomization, concealment of allocation, and blinding, and many did not use intention-to-treat analysis. Most topical treatments used to treat pityriasis versicolor are effective compared with placebo, with numbers needed to treat of 1 to 3. Data suggest that longer durations of treatment and higher concentrations of active agents produce greater cure rates. CONCLUSIONS: Most topical and systemic treatments used for pityriasis versicolor are effective compared with placebo. Randomized controlled clinical trials are needed to establish relative efficacy of topical and systemic agents used for treatment and prevention of pityriasis versicolor.

Willingness-to-pay stated preferences for 8 health-related quality-of-life domains in psoriatic arthritis: a pilot study.

OBJECTIVES: Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis found in up to 5 to 42% of patients with psoriasis. As current instruments do not fully capture health-related quality of life (HR-QOL) in PsA from the patient's perspective, we piloted a novel application of "willingness-to-pay" (WTP) as a Patient Reported Outcome to measure the relative impact of PsA in 8 domains of HR-QOL. METHODS: Fifty-nine PsA patients were interviewed on 8 WTP HR-QOL domains (physical, emotional, sleep, work, social, self-care, intimacy, and concentration). Participants were asked to rank the 8 domains of health in order of HR-QOL impact. In each domain, participants were asked whether PsA affected that domain, whether they were willing to pay for a cure in that domain, and the amount they were willing to pay. Median WTP amounts were compared with the proportion of participants affected by and willing to pay in each domain. Responses in US dollars were interpreted as strength of preference rather than absolute monetary values. RESULTS: The majority of participants were white (98%), > or =45 years of age (70%), insured (98%), and earned >$65,000/yr (66%). The physical domain was most affected by PsA; intimacy and concentration were ranked lowest. Participants reported a wide range of WTP amounts ($0 to $1,000,000), and median WTP amounts were highest in the physical, work, sleep, and self-care domains. Related domains elicited median WTP amounts that were highly correlated. No significant differences in median WTP amounts were found across ages, genders, and income levels for the different domains. CONCLUSIONS: WTP is a novel quantitative patient-perspective measure that is comprehensible and feasible to administer in PsA patients. It represents a unique tool for capturing the complex manifestations of PsA and its impact on the individual, allowing the quantification of specific HR-QOL parameters and providing the potential for comparison across various disease processes in a given individual.