Reactivity Switch in Glycal Dienes toward Different Nucleophiles: Mechanistic Insight and Applications toward the Synthesis of Naphthalene-Fused Pyran Derivatives.

The stereo- and regioselective formation of chiral molecules is an interesting and important topic in organic synthesis due to its wide applicability and intricacy during synthesis. Herein, we disclose a method for the selective functionalization of glycal dienes for synthesizing different glycosides and branched sugars stereo- and regioselectively. The methodology is broad regarding the substrate scope in which various nucleophiles and glycals were explored. Furthermore, we delve into converting the synthesized products into naphthalene-fused pyran derivatives, achieved through a 4 + 2 cycloaddition followed by aromatization. Additionally, we conducted density functional theory studies to gain insight into the formation of regioselective products when different nucleophiles were employed.

Characteristics and Prognosis of Infectious Disease Emergencies in Patients with Chronic Kidney Disease in India.

Objectives: Chronic kidney disease (CKD) significantly increases the risk of infectious diseases (IDs), leading to heightened morbidity and mortality. However, there remains a lack of detailed, region-specific studies. This study investigates the clinical spectrum, etiologies, outcomes, and baseline predictors of mortality of ID emergencies in CKD patients in North India. Methods: This retrospective study was conducted at the Postgraduate Institute of Medical Education and Research, Chandigarh, from January 2021 to December 2022. It included patients aged ≥13 years with CKD and IDs admitted to the Acute Care and Emergency Medicine Unit. Results: We enrolled 248 patients (mean age 50 years, 58.1% males). About 60% had CKD stage 5, and 46% were on maintenance hemodialysis. Diabetic kidney disease was the predominant etiology (38.7%). The principal IDs were pneumonia (27.4%), urinary tract infection (UTI) (21.4%), sepsis of unknown primary focus (15.7%), tuberculosis (8.1%), and multisite infections (7.7%). Patients commonly have atypical clinical presentation, e.g., absence of fever and nonspecific symptoms such as shortness of breath and altered mental status. An emergence of multidrug-resistant organisms, e.g., Enterococcus faecium for UTI and Stenotrophomonas maltophilia for catheter-related bloodstream infections, was noted.In-hospital mortality rate was 33.5%, higher with multisite infections (58%) and pneumonia (47%). A low baseline Glasgow coma scale (GCS) was an independent predictor of mortality [odds ratio (OR) 0.786, 95% confidence interval (CI) 0.693-0.891, p-value <0.001]. Conclusion: Effective management and early intervention are needed to improve outcomes in CKD patients with ID emergencies, given the high mortality and atypical clinical presentations. How to cite this article: Prabhahar A, Vijaykumar NA, Selvam S, Ramchandran R, Sethi J, Pannu AK, et al. Characteristics and Prognosis of Infectious Disease Emergencies in Patients with Chronic Kidney Disease in India. Indian J Crit Care Med 2024;28(6):601-606.

Prevalence of Neurovascular Microemboli After Transcatheter Aortic Valve Replacement.

Background: Neurolotic sequelae after transcatheter aortic valve replacement (TAVR) can cause significant morbidity and mortality. Transcranial Doppler (TCD) imaging can show real-time high intensity transient signals (HITS), which reflect active microembolization. Although it is well known that intraprocedural microembolism occurs, it is not known if this embolic phenomenon continues in the postprocedural period. We investigated whether microemboli occur post-TAVR and whether we could determine any clinical, procedural, or echocardiographic predictors. Methods: We evaluated HITS in 51 consecutive patients undergoing unprotected TAVR with low-, intermediate-, or high-risk Society of Thoracic Surgeons score. Patients were excluded if they did not have temporal windows for insonation of the middle cerebral artery or if they were not willing to participate. Primary outcomes of HITS 24 hours post-TAVR were observed using a Philips iU22 TCD. TCD was performed at 3 time points (pre-, peri-, and post-TAVR) for each patient, before, during, and 24 hours postprocedure. Results: While no HITS were detected in any of the patients preoperatively, all patients had HITS during the procedure. Interestingly, 56.8% had HITS 24 hours post-TAVR. One patient with HITS post-TAVR had a stroke 48 hours after TAVR. Conclusion: We observed a high prevalence of microemboli 24 hours post-TAVR. None of the predictors for intraprocedural microembolism seemed to play an important role for post-TAVR microemboli.

Lumbar Sympathetic Block Leading to Increased Arterial Diameter and Blood Flow: A Mechanism of Therapeutic Benefit.

Lumbar sympathetic blocks (LSBs) have long been used for the treatment of chronic lower extremity pain and for conditions such as complex regional pain syndrome (CRPS). With a better understanding of the autonomic nervous system and its function, these blocks have grown in their utility. Through this growth, however, our understanding of sympathetic-mediated pain is still vaguely understood. Here, we present a case of a patient who underwent a point-of-care ultrasound (POCUS) before and after an LSB, and we were able to show significant dilation of the posterior tibial artery (PTA) following the block. We propose that this arterial dilation plays a mechanistic role in providing pain relief to patients who undergo LSB. This increased blood flow can not only enhance healing properties to surrounding tissues but also allow for nitric oxide to play potential regulatory roles in pain pathways. Here, we also review potential mechanisms of the amelioration of sympathetic-mediated pain as well as the potential utilization of LSBs and neuromodulation in treating visceral pathologies through a better understanding of visceral somatic relationships.

Oxalic acid as a dual C1 surrogate for heterogeneous palladium-catalyzed tandem four-component quinazolinone synthesis.

Herein, a heterogeneous Pd/C-catalyzed direct one-step four-component double carbonylative approach for cascade synthesis of 2-aryl quinazolinones has been reported for the first time starting from 2-iodoaniline derivatives and aryl iodides. The given reaction involves the simultaneous implementation of two different gaseous surrogates i.e., ammonium carbamate as an NH3 precursor and oxalic acid as a bi-functional reagent acting as a CO as well as a C-atom surrogate under ligand-free conditions.

Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial.

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

The Utility of an Epidural Steroid Injection for the Treatment of Idiopathic Brachial Neuritis.

Idiopathic brachial neuritis is an uncommon disorder that predominately affects the superior and middle trunks of the brachial plexus. Severe throbbing and aching shoulder pain is initially present for a period of days to weeks, followed by severe weakness and atrophy that can develop for an extended period of months to years. There are currently no known treatments for brachial neuritis, with the standard of care consisting of analgesics and corticosteroids, which typically provide minimal to no benefit in most cases. In this case, we will present a case of a patient who was diagnosed with idiopathic brachial neuritis and underwent an interlaminar epidural steroid injection (ESI) for treatment. Following treatment with the ESI, the patient had a subsequent resolution of symptoms. This case underscores the value of early recognition for the diagnosis of brachial neuritis and the utility of an ESI as a treatment option, thus preventing long-term pathological sequalae. To our knowledge, this is the first known reported case to have successfully cured brachial neuritis.

Utilization of Truenat chips in defining XDR, pre-XDR and MDR in tuberculous meningitis.

SETTING AND OBJECTIVE: To develop and evaluate newer molecular tests that identify drug resistance according to contemporary definitions in Tuberculous meningitis (TBM), the most severe form of EPTB. DESIGN: 93 cerebrospinal fluid (CSF) specimens [41 culture-positive and 52 culture-negative], were subjected to Truenat MTB Plus assay along with chips for rifampicin, isoniazid, fluoroquinolones and bedaquiline resistance. The performance was compared against phenotypic drug susceptibility testing (pDST), Line probe assay (LPA) and gene sequencing. RESULTS: Against pDST, Truenat chips had a sensitivity and specificity of 100%; 94.47%, 100%; 94.47%, 100%; 97.14% and 100%; 100%, respectively for rifampicin, isoniazid, fluoroquinolones and bedaquiline. Against LPA, all Truenat chips detected resistant isolates with 100% sensitivity; but 2 cases each of false-rifampicin and false-isoniazid resistance and 1 case of false-fluoroquinolone resistance was reported. Truenat drug chips gave indeterminate results in ∼25% cases, which were excluded. All cases reported indeterminate were found to be susceptible by pDST/LPA. CONCLUSION: The strategic drug resistance chips of Truenat Plus assay can contribute greatly to TB elimination by providing rapid and reliable detection of drug resistance pattern in TBM. Cases reported indeterminate require confirmation by other phenotypic and genotypic methods.

Prioritization of sub-watersheds and subsequent site identification for soil water and conservation practices using the SWAT-AHP integrated model in the Lower Sutlej Sub-basin, India.

Prioritization of watersheds is a crucial step in integrated river basin management. It guides resource allocation, planning, decision-making, stakeholder engagement, targeted interventions, and monitoring and evaluation efforts. By identifying and addressing priority watersheds, comprehensive and sustainable management of water resources can be achieved within a river basin. The aim of the current study is to prioritize watersheds using the Soil and Water Assessment Tool (SWAT) and site suitability analysis for the implementation of soil and water conservation structures (SWCS) in the prioritized watersheds by using an analytical hierarchy process (AHP) of the Lower Sutlej Sub-basin, India. The model was calibrated with observed data from 2017 to 2019 with the first 2 years (2015-16) as a warm-up period. Furthermore, validation of the model was done using 2-year data from 2020 to 2021. The model showed successful performance in terms of the R2 range from 0.72 to 0.89, the NSE range from 0.67 to 0.73, the PBIAS range from - 26.70 to 11.30, and the RSR range from 0.51 to 0.57 for stream flow and sediment yield during calibration and validation period. The basin's average annual soil loss ranged from 3.08 to 21.63 t/ha/year, a watershed with the WS2 index seeing the highest rate of soil erosion (21.63 t/ha/year). Hence, WS2 was found to be a top priority. In addition, the site suitability analysis of the prioritized watershed (WS2) reveals that about 1.42% of the area is extremely suitable, 16.14% is highly suitable, and 35.58% is moderately suitable for SWCS. According to the site suitability map validation, both dam locations were found in highly suitable areas, so the developed site suitability map is accurate. This research will help sustainability planners and managers make more informed decisions when building SWCS at suitable sites for better land and water conservation.

Iodine-PEG as a unique combination for the metal-free synthesis of flavonoids through iodonium-triiodide ion-pair complexation.

An efficient metal-free single-step protocol has been developed for the direct synthesis of flavones from 2-hydroxyacetophenone and substituted benzaldehydes. This chemical transformation is exclusively promoted by the iodonium-triiodide ion couple formed through iodine and PEG-400 complexation. The triiodide anion not only helps in the abstraction of a proton from the acetophenone but also promotes the cyclization of intermediate chalcone to the corresponding flavones. The flavones were obtained in very high yields without using any toxic metal catalysts or harsh reaction conditions. The reaction mechanism was established through a series of test reactions and entrapping of reaction intermediates. The developed protocol provides direct access to flavones in high yields under milder reaction conditions with great substrate compatibility, including hydroxylated derivatives.

Novel diagnostic approach for amoebic liver abscess using cell free (cf) DNA: a prospective study.

BACKGROUND: Amoebic liver abscess (ALA) is commonly seen in tropical countries and diagnosis of ALA relies mainly on non-specific serological and imaging techniques as well as PCR from pus. OBJECTIVE: This study evaluated the potential of using cell free DNA (cfDNA) from serum and urine for diagnosing ALA. METHODS: We prospectively evaluated quantitative PCR (qPCR) for detection of cf DNA in serum and urine sample in all liver abscess patients. The samples were collected from patients reporting to emergency ward of Postgraduate Institute of Medical Education and Research, Chandigarh, India with symptoms suggestive of liver abscess. Real time PCR was done to detect cf DNA in serum and urine by targeting 99-bp unit of small subunit rRNA of Entamoeba histolytica and conventional PCR for pus. RESULTS: A total 113 samples (serum and urine) and 100 pus samples were analysed. A total of 62 ALA patients were confirmed; with maximum 57 patients detected by qPCR for cfDNA in the serum, 55 patients by PCR on pus aspirate and 50 ALA patients by qPCR for cfDNA in urine sample. Therefore, the sensitivity of qPCR for detection of cf DNA in serum was 91.94% and for urine was 80.65%. CONCLUSION: A total of 11.2% of ALA patients were diagnosed only through detection of E. histolytica cf DNA in their serum and urine. Detection of cfDNA from serum, urine of ALA has a potential role in future especially for developing countries as it is a rapid, sensitive and patient friendly diagnostic approach.

Sepsis screening tools for predicting infection triggers and outcomes in diabetic ketoacidosis.

Background: An early prediction of infection is challenging in diabetic ketoacidosis (DKA). Methods: This prospective cohort study aimed to assess effectiveness of various sepsis screening tools in predicting infections and prognosis in DKA. Results: Among 141 cases, infection (44.0%) was the commonest precipitating factor. A Sequential Organ Failure Assessment score ≥4 showed high specificity (82.28%) and high positive likelihood ratio (2.64) but limited sensitivity (46.77%). Conversely, Systemic Inflammatory Response Syndrome ≥2 exhibited good sensitivity (95.16%) but a high false-positive rate (84.28%). National Early Warning Score ≥7 and Quick Sequential Organ Failure Assessment ≥2 had low sensitivity and specificity. These sepsis tools also demonstrated low prognostic accuracy for mortality. Conclusion: Sepsis screening tools have limited predictive accuracy for infections and mortality in DKA.

Various clinical tools, including the Sequential Organ Failure Assessment score, Quick Sequential Organ Failure Assessment score, Systemic Inflammatory Response Syndrome criteria and the National Early Warning Score, are used to identify serious infections. This study examined the effectiveness of these tools in patients with diabetic ketoacidosis (DKA), a serious diabetes complication. The study involved 141 patients from north India, and nearly half of them had infections such as pneumonia and urinary tract infections. The researchers found that these tools were not highly effective in identifying infections or predicting deaths among DKA patients at the time of hospital admission. The study suggests that doctors need better ways to diagnose infections in DKA, including more thorough clinical evaluations and advanced tests.

O uso contínuo da terlipressina após a ligadura endoscópica em hemorragia varicosa aguda necessita de mais evidências: um estudo piloto / Rational for continuing terlipressin after endoscopic variceal ligation in acute variceal haemorrhage needs further evidence: a pilot study

ABSTRACT Background Variceal hemorrhage (VH) is a medical emergency. Prompt endoscopic variceal ligation (EVL) is therapeutic. Terlipressin is used in VH and continued for 2—5 days even after EVL. As hemostasis is primarily achieved by EVL, the benefit of continuing trelipressin after EVL is unknown. Objective To evaluate the efficacy of continuing terlipressin after EVL to prevent re-bleed and mortality. Methods In this pilot study, after EVL 74 patients of VH were randomized into two treatment groups TG2 & TG5, received terlipressin (1 mg IV bolus q 4 hourly) for 2 days and 5 days respectively and one control group (TG0), received 0.9% normal saline (10 mL IV bolus q 4 hourly) and followed up for 8 weeks. Results A total of 9 (12.6%) patients had re-bleed with maximum 4 (5.6%) patients in TG5 group followed by 3 (4.2%) in TG2 and 2 (2.8%) in TG0 groups (P=0.670). The overall mortality was 15 (21.1%) patients, 6 (8.5%) patients in TG0 group, followed by 5 (7.0%) in TG5 and 4 (5.6%) in TG2 group (P=0.691). Adverse drug reactions were significantly higher in treatment groups with maximum 18 (24.32%) patients in TG5, followed by 8 (10.8%) in TG2 and 2 (2.7%) in TG0 groups (P=0.00). Duration of hospital stay was also significantly higher in treatment group, 6.63 (±0.65) days in TG5 followed by 3.64 (±0.57) in TG2 and 2.40 (±0.50) days in TG0 groups (P=0.00). Conclusion The rational for continuing terlipressin after EVL is doubtful as it didn't have any benefit for the prevention of re-bleed or mortality; rather it increased the risk of adverse drug reactions and duration of hospital stay. Further randomized clinical trials are encouraged to generate more evidence in support or against continuing terlipressin after EVL.

RESUMO Contexto A hemorragia varicosa (HV) é emergência médica. A ligadura endoscópica imediata das varizes (LEV) é terapêutica. A terlipressina é usada em HV e contínua por 2—5 dias mesmo após a LEV. Como a hemostasia é alcançada principalmente pela LEV, o benefício do uso contínuo da terlipressina após o evento é desconhecido. Objetivo Avaliar a eficácia da terlipressina contínua após a LEV para evitar o ressangramento e a mortalidade. Métodos Neste estudo piloto, após a LEV, 74 pacientes com HV foram randomizados em dois grupos de tratamento TG2 & TG5, que receberam terlipressina (1 mg EV em bolus a cada 4 horas) durante 2—5 dias, respectivamente, e um grupo controle (TG0), que receberam soro fisiológico normal de 0,9% (10 mL EV em bolus a cada 4 horas) e foram seguidos por 8 semanas. Resultados Um total de 9 (12,6%) pacientes tiveram ressangramento, 4 (5,6%) no grupo TG5, seguidos por 3 (4,2%) no TG2 e 2 (2,8%) no grupo TG0 (P=0,670). A mortalidade geral de pacientes foi de 15 (21,1%), 6 (8,5%) no grupo TG0, seguidos por 5 (7,0%) no TG5 e 4 (5,6%) no TG2 (P=0,691). As reações adversas de medicamentos foram significativamente maiores em grupos de tratamento em 18 (24,32%) pacientes no TG5, seguidos por 8 (10,8%) no TG2 e 2 (2,7%) em grupo TG0 (P=0,00). A duração da internação hospitalar também foi significativamente maior no grupo de tratamento, 6,63 (±0,65) dias no TG5, seguido por 3,64 (±0,57) em TG2 e 2,40 (±0,50) dias em grupos TG0 (P=0,00). Conclusão O uso racional para a continuação da terlipressina após a LEV é duvidoso, pois não teve qualquer benefício para a prevenção de ressangramento ou mortalidade; pelo contrário, aumentou o risco de efeitos adversos e duração da internação hospitalar. Outros ensaios clínicos randomizados são necessários para gerar mais evidências em apoio ou contra a terlipressina contínua após a LEV.