Curvilinear regression analysis of benzenoid hydrocarbons and computation of some reduced reverse degree based topological indices for hyaluronic acid-paclitaxel conjugates.

Graph theoretical molecular descriptors alias topological indices are a convenient means for expressing in numerical form the chemical structure encoded in a molecular graph. The structure descriptors derived from molecular graphs are widely used in quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) studies. The reason for introducing new indices is to obtain predictions of target properties of considered molecules that are better than the predictions obtained using already known indices. In this paper, we apply the reduced reverse degree based indices introduced in 2021 by Vignesh et al. In the QSPR analysis, we first compute the reduced reverse degree based indices for a family of benzenoid hydrocarbon molecules and then we obtain the correlation with the Physico-chemical properties of the considered molecules. We show that all the properties taken into consideration for the benzenoid hydrocarbons can be very effectively predicted by the reduced reverse degree based indices. Also, we have compared the predictive capability of reduced reverse degree based topological descriptors against 16 existing degree based indices. Further, we compute the defined reduced reverse degree based topological indices for Hyaluronic Acid-Paclitaxel Conjugates [Formula: see text], [Formula: see text].

Characterizing DRESS syndrome recurrence: a systematic review.

Recurrence of DRESS syndrome is poorly characterized, and dermatologists must be prepared to predict, identify, and manage patients after treatment of the initial presentation. In this study, a primary literature search was conducted using PubMed, capturing all articles recording cases of DRESS syndrome recurrence. Forty-two articles were included for review comprising a total of 60 patients. The average age of patients was 46.3 years and time to recurrence was 123 days. Recurrent episodes presented more frequently with a higher fever and eosinophil absolute peak. Relapse was most often attributed to the introduction of a new medication (n = 18). Of the 17 cases in which outcome data were available, the survival rate of those experiencing recurrence was 71%. Viral reactivation with HHV-6 and organ involvement of the liver were frequently recorded complications. In essence, viral reactivation, severe internal organ involvement, and hematological abnormalities all portended a poorer prognosis in those experiencing DRESS syndrome recurrence. An adequate course of treatment should be maintained until clinical and laboratory parameters normalize, with a slow taper to minimize the likelihood of relapse in those most at risk.

Evaluation of a Case Series of Patients With Generalized Pustular Psoriasis in the United States.

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. RESULTS: Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). CONCLUSIONS AND RELEVANCE: Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.

Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States.

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.

Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

ABSTRACT: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Overlap between hemophagocytic lymphohistiocytosis and drug reaction and eosinophilia with systemic symptoms: a review.

Drug reaction and eosinophilia with systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), shares features with hemophagocytic lymphohistiocytosis (HLH), most notably fever, rash, and internal organ involvement. However, there is increasing recognition of drug-induced (secondary) HLH and biopsy-proven hemophagocytosis in DRESS, suggesting that HLH and DRESS not only overlap but also may be diseases on the same spectrum of immune dysfunction. To characterize existing literature on HLH/DRESS overlap, we queried the PubMed/MEDLINE database for 23 cases of HLH-DRESS codiagnosis. Average time-to-onset of rash after exposure to inciting drug was 2.7 weeks. Fourteen cases (61%) clinically worsened despite initial therapy, prompting a workup with diagnosis of HLH on average 2.3 weeks after diagnosing DRESS. Nine cases met HLH diagnostic criteria and had a RegiSCAR score ≥4. Nine cases met one set of criteria with a presentation suggestive of the other. Five cases met neither criteria. A patient presenting with fever, generalized rash, bicytopenia, and internal organ involvement after drug exposure was most predictive of meeting diagnostic criteria for both HLH and DRESS. Treatment was highly variable, although most initiated systemic corticosteroids with/without IVIG, plasmapheresis, or etoposide. Patients with poor outcomes in this review were treated using steroid monotherapy and had viral reactivation. Dermatologists should consider the possibility of HLH in any patient presenting with fever, rash, internal organ involvement, and cytopenia. Additional studies will be necessary to further characterize HLH and DRESS overlap and determine optimal management.

Pure Endoscopic Supracerebellar Infratentorial Approach to the Pineal Region: A Case Series.

BACKGROUND: Surgical approaches to pineal lesions present a challenge because of limited visibility and maneuverability within the posterior fossa. The supracerebellar infratentorial (SCIT) technique has emerged as an approach to pineal lesions. We aim to demonstrate the efficacy of the endoscopic SCIT technique through a case series conducted at our institution and highlight the advantages of the endoscopic technique over the microscopic alternative. OBJECTIVE: To evaluate the effectiveness and safety of the endoscopic SCIT approach. METHODS: We conducted a retrospective review of pure endoscopic SCIT cases conducted at our institution. Demographic information, preoperative and postoperative imaging, neurological status, surgical data, and complications were recorded. RESULTS: Six patients who underwent pure endoscopic SCIT surgery were identified for analysis. The average lesion volume was 14.12 ± 7.24 cm3. The median postoperative length of stay was 5.0 days. The average surgical duration was 3.54 ± 0.71 hours. All operations were performed in prone position with zero- and 30-degree endoscopes. Pathology included one each of the following lesions: Pineoctyoma, metastatic melanoma, atypical teratoma rhabdoid tumor, ependymoma, epidermoid, abscess. Gross total resection (GTR) was achieved in 5/6 patients, and near-total resection was achieved in 1/6 patients. Surgical complications included one case of postoperative infection. CONCLUSION: The purely endoscopic SCIT approach is a safe and effective approach for deep-seated pineal lesions. This approach allows for visibility and maneuverability around the lesion and facilitates high rates of GTR.

Stevens-Johnson syndrome and toxic epidermal necrolysis-like reactions to checkpoint inhibitors: a systematic review.

The use of checkpoint inhibitors for treatment of advanced malignancies is increasing. Rashes, pruritus, and more rarely, reactions resembling Stevens-Johnsons syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur secondary to checkpoint inhibitors. To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of SJS or TEN associated with checkpoint inhibitors. We identified 18 cases of SJS or TEN-like reactions to checkpoint inhibitors in the literature. There were 12 cases of SJS-like rashes with median time to onset of 5.6 weeks (average of 8.9 weeks), of which five were delayed to week 8 or later from checkpoint inhibitor initiation. The five TEN-like reactions had a median time to onset of 4 weeks (average of 5.38 weeks), of which two were delayed to week 6 or later. SJS/TEN-like reactions to nivolumab (seven cases) had median onset time of 3 weeks, whereas five cases secondary to pembrolizumab had median onset time of 11 weeks. Seven cases in this study described prodromal rashes, which varied from localized papular rashes to generalized morbilliform rashes, prior to evolution into SJS or TEN-like patterns. SJS-like patterns generally improved well on systemic treatment/supportive care and no cases of death were identified, but mortality occurred in three of five patients with TEN-like reactions. Dermatologists should consider the possibility for unique features of SJS/TEN in response to checkpoint inhibitors. Additional studies will be necessary to further characterize SJS/TEN-like eruptions on checkpoint inhibitors and determine the optimal management of these cases.

Neutrophilic dermatoses as adverse effects of checkpoint inhibitors: A review.

Checkpoint inhibitors are a new class of drugs that enhance the immune system's intrinsic ability to destroy tumor cells by blocking signaling through the programmed cell death (PD-1) receptor, its ligand (PD-L1), and the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). The resulting increase in immunologic activity is responsible for a variety of adverse cutaneous reactions, which sometimes include neutrophilic dermatoses. We queried the PubMed database for existing cases of checkpoint inhibitors causing neutrophilic dermatoses. The literature search identified four cases of Sweet syndrome, four cases of pustular eruptions, two cases of pyoderma gangrenosum, and one case of bullous lupus erythematosus secondary to checkpoint inhibitors. All neutrophilic dermatoses were treated with topical or systemic steroids and most (9 of 11) completely resolved. Dermatologists should be aware of these rare, adverse cutaneous reactions to checkpoint inhibitors and how to approach their treatment, especially as their use increases.

SCN11A Arg225Cys mutation causes nociceptive pain without detectable peripheral nerve pathology.

OBJECTIVE: The SCN11A gene encodes the NaV1.9 sodium channel found exclusively in peripheral nociceptive neurons. METHODS: All enrolled participants were evaluated clinically by electrophysiologic studies, DNA sequencing, and punch skin biopsies. RESULTS: All affected family members are afflicted by episodes of pain. Pain was predominantly nociceptive, but not neuropathic in nature, which led a diagnosis of fibromyalgia in some patients. All patients had normal findings in nerve conduction studies for detecting large nerve fiber neuropathies and skin biopsies for detecting small nerve fiber pathology. CONCLUSIONS: Unlike those patients with missense mutations in SCN11A, small fiber sensory neuropathy, and neuropathic pain, the Arg225Cys SCN11A in the present study causes predominantly nociceptive pain with minimal features of neuropathic pain and undetectable pathophysiologic changes of peripheral neuropathy. This finding is consistent with dysfunction of nociceptive neurons. In addition, since nociceptive pain in patients has led to the diagnosis of fibromyalgia, this justifies a future search of mutations of SCN11A in patients with additional pain phenotypes such as fibromyalgia to expand the clinical spectrum beyond painful small fiber sensory neuropathy.

Myelin abnormality in Charcot-Marie-Tooth type 4J recapitulates features of acquired demyelination.

OBJECTIVE: Charcot-Marie-Tooth type 4J (CMT4J) is a rare autosomal recessive neuropathy caused by mutations in FIG4 that result in loss of FIG4 protein. This study investigates the natural history and mechanisms of segmental demyelination in CMT4J. METHODS: Over the past 9 years, we have enrolled and studied a cohort of 12 CMT4J patients, including 6 novel FIG4 mutations. We evaluated these patients and related mouse models using morphological, electrophysiological, and biochemical approaches. RESULTS: We found sensory motor demyelinating polyneuropathy consistently in all patients. This underlying myelin pathology was associated with nonuniform slowing of conduction velocities, conduction block, and temporal dispersion on nerve conduction studies, which resemble those features in acquired demyelinating peripheral nerve diseases. Segmental demyelination was also confirmed in mice without Fig4 (Fig4-/- ). The demyelination was associated with an increase of Schwann cell dedifferentiation and macrophages in spinal roots where nerve-blood barriers are weak. Schwann cell dedifferentiation was induced by the increasing intracellular Ca2+ . Suppression of Ca2+ level by a chelator reduced dedifferentiation and demyelination of Schwann cells in vitro and in vivo. Interestingly, cell-specific knockout of Fig4 in mouse Schwann cells or neurons failed to cause segmental demyelination. INTERPRETATION: Myelin change in CMT4J recapitulates the features of acquired demyelinating neuropathies. This pathology is not Schwann cell autonomous. Instead, it relates to systemic processes involving interactions of multiple cell types and abnormally elevated intracellular Ca2+ . Injection of a Ca2+ chelator into Fig4-/- mice improved segmental demyelination, thereby providing a therapeutic strategy against demyelination. Ann Neurol 2018;83:756-770.