Effectiveness of Gabapentin as a Benzodiazepine-Sparing Agent in Alcohol Withdrawal Syndrome.

Background and Objectives: Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Materials and Methods: Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. Results: A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose (p < 0.01)). However, there were no significant differences in outcomes between the two groups. Conclusions: Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation.

Isolated IgG4 related disease of the trachea.

IgG4 related disease (IgG4-RD) is a multisystem inflammatory disease and can affect several organs including salivary glands, orbits, lungs, pancreas, kidneys and lymph nodes. Up to 40 % of patients have allergic manifestations including asthma, chronic rhinosinusitis, eczema and asthma. Commonly pulmonary manifestations include pulmonary nodules ranging from <1 to 5 cm in diameter, interstitial opacities and mediastinal lymphadenopathy. Rarely, IgG4-RD presents as isolated tracheal disease. Symptoms include dyspnea and stridor due to airway narrowing. Diagnosis of IgG4-RD including tracheal IgG4-RD requires a biopsy. The histologic specimen is characterized by lymphoplasmacytic infiltrate with high density of IgG4 positive plasma cells, and storiform fibrosis (a cartwheel appearance of fibroblasts and inflammatory cells). Up to 30 % of patients with IgG4-RD have normal serum IgG4 levels. The mainstay of therapy is glucocorticoids for those with systemic disease. Rituximab is an alternative for those who cannot tolerate glucocorticoids or those with disease recurrence. Patients with tracheal disease often require balloon dilation. Recurrence is common in patients and up to two thirds of patients have residual disease despite treatment. These patients often require surgical resection of affected area for symptomatic relief.

Visible-Light-Induced Radical Sulfonylative-Cyclization Cascade of 1,6-Enynol Derivatives with Sulfinic Acids: A Sustainable Approach for the Synthesis of 2,3-Disubstituted Benzoheteroles.

Benzoheteroles are promising structural scaffolds in the realm of medicinal chemistry, but sustainable synthesis of 2,3-difunctionalized benzoheterole derivatives is still in high demand. Indeed, we have conceptually rationalized the intrinsic reactivity of propargylic-enyne systems for the flexible construction of 2,3-disubstituted benzoheteroles through radical sulfonylative-cyclization cascade under organophotoredox catalysis. We hereby report an efficient visible-light-induced sulfonyl radical-triggered cyclization of 1,6-enynols with sulfinic acids under the dual catalytic influence of 4CzIPN and NiBr2⋅DME, which led to the formation of 2,3-disubstituted benzoheteroles in good to high yields. Additionally, the Rose Bengal (RB)-catalyzed radical sulfonylative-cycloannulation of acetyl-derived 1,6-enynols with sulfinic acids under blue LED irradiation allowed to access 3-(E-styryl)-derived benzofurans and benzothiophenes in moderate to good yields. The scope and limitations of the present strategies were successfully established using different classes of 1,6-enynols and sulfinic acids bearing various sensitive functional groups, yielding the desired products in a highly stereoselective fashion. Plausible mechanistic pathways were also proposed based on the current experimental and control experiments.

Impact of Virtual Interviews on Pulmonary and Critical Care Fellowship Match: An Analysis of National Data.

Background: Internal Medicine residents have historically expressed hesitancy in pursuing a career in pulmonary and critical care medicine (PCCM). However, recent studies have demonstrated newfound competitiveness. The coronavirus disease (COVID-19) global outbreak prompted the implementation of a virtual interviewing model for PCCM fellowship match. The effect of this new paradigm on PCCM match results has not been studied previously. Objective: With the shift to virtual interviewing, we aim to determine how this new method of interviewing may influence the selection of candidates for fellowship training programs. Methods: We acquired data of 4,333 applicants ranking PCCM for the years 2017-2021 from the National Resident Matching Program and the Electronic Residency Application Service websites for the years 2017-2021. Chi-square (χ2) analysis of the applicants' demographics and the percentage of applicants matching at their first choice versus those who matched at lower than their third-choice program before and after the implementation of virtual interviews season was performed. Results: The matching probability for the U.S. Doctors of Osteopathic Medicine significantly increased after the implementation of virtual interviews compared with the years 2017-2020 (χ2 = 8.569; P = 0.003). The matching probability remained unchanged for U.S. Doctors of Medicine (χ2 = 2.448; P = 0.118). Overall, an applicant's probability of matching at their first choice has significantly decreased after the virtual interview format (χ2 = 4.14; P = 0.04). Conversely, the probability of matching at a program that is lower than the third choice has significantly increased (χ2 = 11.039; P < 0.001). Conclusion: Our study provides evidence regarding the effect of the virtual interview format on PCCM match results. Strikingly, applicants are more likely to match at lower-ranked programs in their rank list after the implementation of the virtual interview process. These results can be helpful for both programs and applicants, to guide their future expectations and decisions while going through the interview process.

Recent trends in the synthesis and applications of ß-iodovinyl sulfones: a decade of progress.

Direct vicinal difunctionalization of π-systems has emerged as a powerful platform for constructing multiple bonds in a single synthetic operation using simple chemical feedstocks. Over the past decade, there has been exponential growth in the direct construction of successive C-S and C-I bonds using a wide variety of sulfonyl and iodide reactants through 1,2-iodosulfonylation of alkynes in a regio- and stereo-selective manner. In this review, we mainly focus on the recent developments in the preparation of ß-iodovinyl sulfones and their practical applications in organic synthesis. The most promising photoredox and electrochemical transformations for synthesizing ß-iodovinyl sulfones are also reviewed. The multifunctional ß-iodovinyl sulfones have recently been burgeoning as versatile synthetic precursors due to the combination of vinyl iodide and vinyl sulfone moieties, essential building blocks for diverse synthetic manipulations. We hereby present the chemistry of ß-iodovinyl sulfones, which can be classified into numerous sections based on the sulfonyl surrogates, and potential synthetic approaches are systematically outlined.

Epidemiology and Clinical Outcomes of Fusobacterium Infections: A Six-Year Retrospective Study.

Background and Objectives: Anaerobic bacteria like Fusobacterium can lead to severe and life-threatening infections. The inherent complexities in the isolation of these bacteria may result in diagnostic and therapeutic delays, thereby escalating both morbidity and mortality rates. We aimed to examine data from patients with infections due to Fusobacterium to gain insights into the epidemiology and clinical outcomes of patients with these infections. Methods and Results: We conducted a retrospective analysis of clinical data from a cohort of patients with cultures positive for Fusobacterium species at a tertiary care medical center in the United States. Between 2009 and 2015, we identified 96 patients with cultures positive for Fusobacterium. Patients could be categorized into three groups based on the site of primary infection. Patients with head and neck infections constituted 37% (n 36). Patients with infections of other soft tissue sites accounted for 38.5% (n 37). Patients with anaerobic bacteremia due to Fusobacterium formed 24% (n 23) of the cohort. Surgical intervention coupled with antibiotic therapy emerged as cornerstones of management for patients with head and neck or other soft tissue infections, who generally exhibited more favorable outcomes. Patients with bacteremia were older, more likely to have malignancy, and had a high mortality rate. When speciation was available, Fusobacterium necrophorum was the most frequently isolated species. Conclusions: Our retrospective analysis of epidemiology and clinical outcomes of Fusobacterium infections revealed three distinct cohorts. Patients with head, neck, or soft tissue infections had better outcomes than those with bacteremia. Our findings highlight the importance of employing management strategies based on infection site and underlying comorbidities in patients with Fusobacterium infections. Further research is needed to investigate the optimal therapeutic strategies and identify prognostic indicators to improve clinical outcomes for these complex infections.

A Unique Case of Prostate Carcinoma Presenting as Retroperitoneal Lymphadenopathy With Normal Levels of Prostate-Specific Antigen and a Prostate of Normal Size: A Case Report.

Despite the significant advancements in prostate-specific antigen (PSA) screening and the diverse array of available treatments, prostate cancer (PCa) still significantly contributes to cancer-related illness. The most prevalent sites for metastases are bones, distant lymph nodes, and abdominal organs. Nevertheless, metastasis to the renal and retroperitoneal regions originating from prostate cancer constitutes an exceptionally uncommon clinical occurrence. Metastatic PCa commonly presents with elevated serum PSA levels, a hallmark of its diagnostic profile. However, there are instances where patients exhibit atypical metastatic patterns or maintain normal PSA levels. In the case under consideration, the patient exhibited a periureteral tumor with an indeterminate primary origin, subsequently confirmed to be metastatic prostate cancer. This case underscores the importance of recognizing the varied and sometimes elusive presentations of metastatic PCa. Despite its rarity, the occurrence of renal and retroperitoneal metastasis emphasizes the need for vigilance and a comprehensive understanding of the diverse manifestations of advanced PCa for timely and accurate diagnosis, which is paramount in optimizing patient care and outcomes.

Echocardiography and pulmonary hypertension in patients with chronic obstructive pulmonary disease undergoing lung transplantation evaluation.

BACKGROUND: The use of echocardiography in pulmonary hypertension (PH) in advanced chronic obstructive pulmonary disease (COPD) is understudied. We aimed to compare the performance of echocardiography with right heart catheterization (RHC) in the diagnosis of PH in COPD patients undergoing lung transplant evaluation. METHODS: We included 111 patients with severe COPD who underwent RHC in a single center as part of lung transplantation evaluation. COPD-PH and severe COPD-PH were defined based on RHC per the 6th world symposium on pulmonary hypertension. Echocardiographic probability of PH was described according to the European Society of Cardiology guidelines. Summary and univariate analyses were performed. RESULTS: The mean age (±SD) was 62 (8) and 47% (n=52) were men. A total of 82 patients (74 %) had COPD-PH. The sensitivity, specificity, positive predictive, and negative predictive values of echocardiography in diagnosing COPD-PH were 43 %, 83 %, 88 %, and 34 % respectively and for severe COPD-PH were 67 %, 75 %, 50 %, and 86 % respectively. Echocardiography was consistent with RHC in ruling in/out PH in 53% (n=59) of patients. After controlling for age, sex. BMI, pack year, echocardiography-RHC time difference, GOLD class, FVC, and CT finding of emphysema, higher TLC decreased consistency (parameter estimate=-0.031; odds ratio: 0.97, 95%CI 0.94-0.99; p=0.037) and higher DLCO increased consistency (parameter estimate=0.070; odds ratio: 1.07, 95%CI 0.94-0.99; p=0.026). CONCLUSIONS: Echocardiography has high specificity but low sensitivity for the diagnosis of PH in advanced COPD. Its performance improves when ruling out severe COPD-PH. This performance correlates inversely with lung hyperinflation.

Fluid Resuscitation and Sepsis Management in Patients with Chronic Kidney Disease or End-Stage Renal Disease: Scoping Review.

Managing sepsis and fluid resuscitation in patients with chronic kidney disease or end-stage renal disease is challenging for health care providers. Nurses are essential for early identification and treatment of these patients. Nurse education on assessing perfusion and implementing 3-hour bundled care can improve mortality rates in patients with sepsis. In this scoping review, initial screening identified 1176 articles published from 2015 through 2023 in the National Library of Medicine database; 29 articles were included in the literature summary and evidence synthesis. A systematic review meta-analysis was not possible because of data heterogeneity. The review revealed that most patients with chronic kidney disease or end-stage renal disease received more conservative resuscitation than did the general population, most likely because of concerns about volume overload. However, patients with chronic kidney disease or end-stage renal disease could tolerate the standard initial fluid resuscitation bolus of 30 mL/kg for sepsis. Outcomes in patients with chronic kidney disease or end-stage renal disease were similar to outcomes in patients without those conditions, whether they received standard or conservative fluid resuscitation. Patients who received the standard (higher) fluid resuscitation volume did not have increased rates of complications such as longer duration of mechanical ventilation, increased mortality, or prolonged length of stay. Using fluid responsiveness to guide resuscitation was associated with improved outcomes. The standard initial fluid resuscitation bolus of 30 mL/kg may be safe for patients with chronic kidney disease or end-stage renal disease and sepsis. Fluid responsiveness could be a valuable resuscitation criterion, promoting better decision-making by multidisciplinary teams. Further research is required.

Effect of Obesity on Mortality in Pulmonary Hypertension-A Systematic Review and Meta-Analysis.

Obesity is reported to have a protective effect on mortality in pulmonary hypertension (PH), a phenomenon known as obesity paradox. However, the data are conflicting, with some studies showing decreased mortality while other studies found no effect of obesity on mortality. Therefore, we performed a systematic review and meta-analysis to examine whether there is an association between obesity and mortality in PH. Only patients with PH diagnosed by right heart catheterization were included. We also performed a sub-group analysis of subjects with pre-capillary PH only. A total of six studies met the inclusion criteria, with a sample size of 13,987 patients. Obese subjects had lower mortality compared to non-obese subjects in the combined pre- and post-capillary PH group (hazard ratio 0.79, 95% CI 0.66-0.95, p = 0.01). While obesity was associated with reduction in mortality in the pre-capillary PH group (hazard ratio 0.77, 95% CI 0.60 to 0.98, p = 0.03), this was not uniform across all studies.

Pd(II)-Catalyzed Tandem Cycloannulative-Alkenylation of o-Alkynyl-Phenols/Anilines with (E)-ß-Iodovinyl Sulfones: A Direct Strategy To Construct 3-(Vinyl sulfonyl)benzoheterole Derivatives.

Benzoheteroles and vinyl sulfones are the most promising pharmaceutical relevance motifs, yet the hybrid analogues of these scaffolds still need to be explored. We report herein a general and highly efficient Pd(OAc)2-catalyzed intramolecular cyclization and vinylation of o-alkynylphenols/o-alkynylanilines with (E)-ß-iodovinyl sulfones under mild reaction conditions. A direct C(sp2)-C(sp2) cross-coupling is enabled for the diversity-oriented synthesis of vinyl sulfone-tethered benzofurans and indoles in good to high yields with excellent stereoselectivity. Notably, this tandem process was consistent at the gram scale, and in situ, generation of 2-(phenylethynyl)phenol has also been utilized in a scalable synthesis. Late-stage synthetic transformations were also further explored, including isomerization and desulfonylative-sulfenylation. Moreover, several control experiments were accomplished, and we proposed a plausible mechanism based on existing experimental results.

Mn(OAc)3-Mediated Unexpected Cycloannulative Sulfonyl Migration Cascade using (E)-ß-Iodovinyl Sulfones and ortho-Alkynylphenols for Direct Synthesis of Chromene-Derived Vinyl Sulfones.

Cycloannulative sulfonyl migration has received much attention; however, a carbon-to-carbon sulfonyl group shift still needs to be discovered. We hereby report a base-mediated oxa-Michael addition-elimination of (E)-ß-iodovinyl sulfones with ortho-alkynylphenols, followed by cycloisomerization and unique stereoselective sulfonyl migration in one-pot, is realized under the influence of Mn(OAc)3·2H2O. A broad range of vinyl sulfone-tethered chromenes were readily accessed in moderate to high yields with good functional group compatibility. Notably, the reaction was robust at the gram scale, and postsynthetic transformations were successfully uncovered. Moreover, plausible mechanistic pathways were rationalized on the basis of existing experimental results.

Unified Radical Sulfonylative-Annulation of 1,6-Enynols with Sodium Sulfinates: A Modular Synthesis of 2,3-Disubstituted Benzoheteroles.

Benzoheteroles are valuable scaffolds in medicinal chemistry, but the direct synthesis of 3-vinyl benzoheterole analogues remains unexplored. A rationally designed new class of 1,6-enyne-containing propargylic alcohols has been prepared for the modular synthesis of 3-alkenyl benzoheteroles. Ag-catalyzed cascade radical sulfonylative-cycloannulation of 1,6-enynols with sodium sulfinates is realized to access a wide variety of 2,3-disubstituted benzoheteroles in good to high yields. Moreover, a three-component coupling of 1,6-enynols, aryldiazonium salts, and Na2S2O5 (as an SO2 surrogate) has been achieved to deliver benzoheterole derivatives in moderate to good yields. Of note, a scalable reaction and late-stage synthetic transformations were successfully demonstrated. A plausible mechanism is also presented based on the existing experimental results and control experiments.

Hypersensitivity Pneumonitis With and Without Autoimmune Features: A Clinical Comparative Analysis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by an immunological reaction to repeated inhalational exposure to antigens. The etiology and exact immunopathology are poorly understood. Autoimmunity overlapping with HP has been described but the role of concomitant autoimmunity in the clinical course and outcome of the HP is not clearly established. In this study, we examined patients diagnosed with HP and compare them to patients with concomitant HP and autoimmunity. METHODS: Patients were retrospectively screened from a single-center ILD registry. Patients > 18 years with an established multidisciplinary diagnosis of HP were included in the study. Patients with HP without autoimmune features and patients with HP with autoimmune features (HPAF) were assessed. We compared the demographics, clinical characteristics, treatment, and outcomes between the two groups. We used a Cox proportional hazards model to compare lung transplant-free survival outcomes of patients with HPAF to those with non-HPAF HP patients. RESULTS: Of 73 patients with HP, 43 were diagnosed with HPAF. Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to non-HPAF HP patients [48.8 vs 23.3%, p = 0.028, Crude odds ratio (cOR) = 3.14]. Symptomatically, those with HPAF reported a higher prevalence of arthritis as compared to non-HPAF HP (20.9 vs 3.3%, p = 0.040, cOR = 7.68). No significant differences between pulmonary function tests, oxygen requirements, mortality, and lung transplantation rates were found between the two groups. There was no statistically significant difference in transplant-free survival (p = 0.836). CONCLUSION: Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to patients with non-HPAF HP. The clinical characteristics and outcomes did not differ between the two groups and concomitant autoimmunity among the HP group did not portend a poorer prognosis.

Ascertainment of vaccination status by self-report versus source documentation: Impact on measuring COVID-19 vaccine effectiveness.

BACKGROUND: During the COVID-19 pandemic, self-reported COVID-19 vaccination might facilitate rapid evaluations of vaccine effectiveness (VE) when source documentation (e.g., immunization information systems [IIS]) is not readily available. We evaluated the concordance of COVID-19 vaccination status ascertained by self-report versus source documentation and its impact on VE estimates. METHODS: Hospitalized adults (≥18 years) admitted to 18 U.S. medical centers March-June 2021 were enrolled, including COVID-19 cases and SARS-CoV-2 negative controls. Patients were interviewed about COVID-19 vaccination. Abstractors simultaneously searched IIS, medical records, and other sources for vaccination information. To compare vaccination status by self-report and documentation, we estimated percent agreement and unweighted kappa with 95% confidence intervals (CIs). We then calculated VE in preventing COVID-19 hospitalization of full vaccination (2 doses of mRNA product ≥14 days prior to illness onset) independently using data from self-report or source documentation. RESULTS: Of 2520 patients, 594 (24%) did not have self-reported vaccination information to assign vaccination group; these patients tended to be more severely ill. Among 1924 patients with both self-report and source documentation information, 95.0% (95% CI: 93.9-95.9%) agreement was observed, with a kappa of 0.9127 (95% CI: 0.9109-0.9145). VE was 86% (95% CI: 81-90%) by self-report data only and 85% (95% CI: 81-89%) by source documentation data only. CONCLUSIONS: Approximately one-quarter of hospitalized patients could not provide self-report COVID-19 vaccination status. Among patients with self-report information, there was high concordance with source documented status. Self-report may be a reasonable source of COVID-19 vaccination information for timely VE assessment for public health action.

An Atypical Source of Persistent Fungemia in the Intensive Care Unit.

BACKGROUND Candidemia is a common complication of critically ill and immunocompromised patients, with more than 50% associated mortality. Typical etiologies include valvular vegetations, intra-abdominal fluid collections, and central venous catheters. Treatment often entails surgical excision, but anticoagulation may be sufficient. CASE REPORT Our case was a 63-year-old woman with diabetes mellitus, left hip osteoarthritis status after hemiarthroplasty, and alcohol use disorder, admitted to the Intensive Care Unit with diabetic ketoacidosis (DKA) and hemorrhagic shock from an upper gastrointestinal bleed. Complicating her course was the development of Candida species fungemia. An extensive workup including transthoracic echocardiography, computed tomography of the chest, abdomen, and pelvis, ocular examination, and hip aspiration was unrevealing in determining the etiology. Despite early line removal and appropriate antifungal therapy, the fungemia persisted. A broader evaluation revealed a venous thromboembolism, which ultimately was thought to be the source. Subsequent initiation of anticoagulation and continued antifungal therapy led to clearance of blood cultures with overall clinical improvement. CONCLUSIONS In critically ill patients at higher risk for development of venous thromboembolism, septic thrombi should be considered in the differential diagnosis when evaluating for source control in a patient with fungemia.

Echocardiographic characteristics of patients with antisynthetase syndrome.

Right ventricular (RV) dysfunction and pulmonary hypertension (PH) occurs in approximately one-third of patients with interstitial lung disease (ILD) and is associated with reduced 6-minute walk distance (6MWD), and increased hospitalizations and mortality. Although the impact of RV dysfunction and PH has been well described in several types of ILD, data is scarce on antisynthetase syndrome. Therefore, we sought to examine the presence of RV dysfunction and PH in patients with antisynthetase syndrome and the impact on clinical outcomes. We conducted a retrospective study of patients with antisynthetase syndrome. Seventy-five subjects were identified. Fifty-one (68%) subjects had echocardiographic data. Patients were grouped into those with normal fractional area change (FAC) ≥ 35% and reduced FAC < 35%. Clinical, echocardiographic, and right heart catheterization data were compared between the two groups. Subjects with FAC < 35% had lower diffusion capacity of the lung for carbon monoxide (29% vs. 47%, p = 0.004), fibrotic features on computed tomography of the chest (79% vs. 33%, p = 0.005), larger RV diameter (5.4 vs. 3.9 cm, p < 0.001), higher right atrial pressures (8 vs. 5 mmHg, p = 0.02), and required supplemental oxygen more frequently (100% vs. 44%, p < 0.001) compared to those with FAC ≥ 35%. We found no difference in 6MWD and hospitalizations between the two groups. The presence of RV dysfunction in antisynthetase syndrome may identify patients at risk of poor outcomes.

Nonimaging Diagnostic Tests for Pneumonia.

This article reviews the various nonimaging diagnostic tests available for the diagnosis of pneumonia including the methods by which specimens are obtained and the speed at which certain tests are available. Because tests results may be available at the time of radiologic image interpretation, it is important for the radiologist to be aware of the type of specimens and diagnostic tests to search for in the electronic medical record in order to provide a more refined imaging report. Diagnostic tests for the most common bacterial, fungal, viral, and parasitic infections are discussed.

Base-mediated [3 + 2]-cycloannulation strategy for the synthesis of pyrazolo[1,5-a]pyridine derivatives using (E)-ß-iodovinyl sulfones.

Pyrazolo[1,5-a]pyridines continue to occupy a special place in medicinal chemistry, but the direct construction of 3-sulfonyl analogues remains unexplored. Under basic conditions, pyridinium-N-amine and the corresponding dipolar aminide played a vibrant role in [3 + 2]-cycloaddition using (E)-ß-iodovinyl sulfones. K2CO3-mediated tandem cycloannulative-desulfonylation of (E)-ß-iodovinyl sulfones with 1-aminopyridinium iodide is realized to access 2-substituted pyrazolo[1,5-a]pyridines in good to high yields. An essential modification of the dipolar N-tosylpyridinium imide allows the first preparative synthesis of 3-sulfonyl-pyrazolo[1,5-a]pyridines in moderate to high yields. Of note, the metal-free protocol features a broad substrate scope with good functional group tolerance and compatibility. The efficacy of the process was proved with gram-scale reactions, and a plausible mechanism is also presented based on concrete results.

5-Fluorouracil Neurotoxicity in the Absence of Dihydropyrimidine Dehydrogenase Deficiency Case Report.

5 fluorouracil (5-FU)-related neurotoxicity is a rare and severe complication of 5-FU administration. Dihydropyrimidine dehydrogenase (DPD) deficiency is associated with an increased risk of serious adverse reactions due to its role in 5-FU metabolism. We report a case of acute reversible neurotoxicity with global areas of diffusion restriction in a patient with colorectal adenocarcinoma being treated with leucovorin calcium, 5-fluorouracil, and oxaliplatin (FOLFOX) without DPD deficiency following uridine triacetate administration.