Clostridium difficile Infection: Risk and Poor Prognostic Factors at a Tertiary Hospital in the Eastern Region of Saudi Arabia.

BACKGROUND:  Clostridium difficile (C. difficile) is a common cause of hospital-acquired diarrhea. It is associated with significantly higher mortality and morbidity in addition to the cost-effectiveness burden on the healthcare system. The primary risk factors for C. difficile infection (CDI) are past C. difficile exposure, proton pump inhibitors, and antibiotic usage. These risk factors are also associated with poor prognosis. OBJECTIVE: This study was performed in Dr. Sulaiman Al Habib Tertiary Hospital in the Eastern Region of Saudi Arabia. The aim was to evaluate the risk and prognostic factors of CDI and their association with the outcomes of hospital stay, such as complications, length of stay (LOS), and treatment duration. PATIENTS AND METHODS: This is a retrospective cohort study for all patients who tested for C. difficile in the medical department. The target population was all adult patients ≥16 years with positive stool toxins for C. difficile between April 2019 and July 2022. The main outcome measures are risk and poor prognostic factors for CDI. RESULTS: C. difficle infection patients were included in the study; 12 (52.2%) were female, and 11 (47.8%) were male. The mean age of the patients was 58.3 (SD: 21.5) years; 13 (56.5%) patients were below 65 years, and 10 were above 65 years. Only four patients were without comorbidities, and 19 (82.6%) patients had various comorbidities. Importantly, hypertension was the most common comorbidity in 47.8% of the patients. Furthermore, advanced age significantly impacted the hospital LOS as the mean age among patients who stayed at the hospital less than four days and those who stayed ≥4 days was 49.08 (19.7) and 68.36 (19.5), respectively (P = .028). CONCLUSION:  Advanced age was the most frequent poor prognostic factor among our inpatient participants with positive CDI. It was significantly associated with longer hospital LOS, more complications, and longer treatment duration.

Plant functional trait responses to cope with drought in seven cool-season grasses.

In semi-arid and arid regions, the selection of suitable grass species with high-yield production, tolerance to drought stress, and potential for recovery from drought is of special importance. Despite extensive research in cool-season grasses, inter-species differences in post-drought recovery, persistence, survival, and summer dormancy and their relationship with drought tolerance need more investigation. In the present study, 28 diverse genotypes belonged to seven cool-season grass species, including Festuca arundinacea (tall fescue), Festuca pratensis (meadow fescue), Festuca ovina (sheep fescue), Festuca rubra (red fescue), Lolium perenne (perennial ryegrass), Lolium multiflorum (Italian ryegrass) and Lolium × hybridum were evaluated during 2016-2019 under three irrigation regimes (normal, mild, and intense drought stress). Then in the fourth year (on August 2019), irrigation was withheld at all previous irrigation regimes for two months during summer, and then species were re-irrigated to study the effect of prolonged drought conditions. A wide range of genetic diversity was detected in all the measured traits among and within species in response to different irrigation levels. Recurrent drought stress decreased forage productivity, post-drought recovery, and survival in all grass species. Among the studied species, tall fescue had higher forage production, drought tolerance, survival, recovery rate, and persistence. Sheep fescue had low forage production and recovery after drought. Drought tolerance (based on stress tolerance score, STS) was highly associated with forage yield and post-drought recovery and partially with summer dormancy under both mild and intense drought stress conditions. This indicated that selection based on higher STS would lead to choosing genotypes with better recovery after prolonged drought. Superior species and preferable genotypes for forage use from species Festuca arundinacea and for turf application from species Festuca arundinacea, Lolium perenne and Lolium × hybridum were identified across different water environments for future programs.

Genetic parameters and selection in full-sib families of tall fescue using best linear unbiased prediction (BLUP) analysis.

BACKGROUND: Better understanding of genetic structure of economic traits is crucial for identification and selection of superior genotypes in specific breeding programs. Best linear unbiased prediction (BLUP) is the most efficient method in this regard, which is poorly used in forage plant breeding. The present study aimed to assess genetic variation, estimate genetic parameters, and predict breeding values of five essential traits in full sib families (recognized by EST-SSR markers) of tall fescue using REML/BLUP procedure. METHOD: Forty-two full-sib families of tall fescue (included of 120 individual genotypes), recognized by EST-SSR markers along with twenty-one their corresponding parental genotypes were assessed for biomass production and agro-morphological traits at three harvests (spring, summer, and autumn) in the field during 4 years (2017-2020). RESULTS: Considerable genotypic variability was observed for all traits. Low narrow-sense heritability (h2n) for dry forage yield (DFY) at three harvest indicates that non-additive gene actions may play an important role in the inheritance of this trait. Higher h2n of yield related traits and flowering time and also significant genetic correlation of these traits with forage yield, suggests that selection based on these traits may lead to indirect genetic improvement of DFY. CONCLUSION: Our results showed the adequacy of REML/BLUP procedure for identification and selection of preferable parental genotypes and progenies with higher breeding values for future breeding programs such as variety development in tall fescue. Parental genotypes 21 M, 1 M, and 20 L were identified as superior and stable genotypes and could also produce the best hybrid combinations when they were mostly used as maternal parent.

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis.

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.

Bifunctional Therapeutic Peptide Assembled Nanoparticles Exerting Improved Activities of Tumor Vessel Normalization and Immune Checkpoint Inhibition.

The effectiveness of cancer immunotherapy is impaired by the dysfunctional vasculature of tumors. Created hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in tumor tissue. Structural and functional normalization of abnormal tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the hypoxia in the tumor site and increasing infiltration of antitumor T cells. Taking advantage of peptide amphiphiles, herein, a novel peptide amphiphile nanoparticle composed of an antiangiogenic peptide (FSEC) and an immune checkpoint blocking peptide (D PPA) is designed and characterized. FSEC peptide is known to be involved in vessel normalization of tumors in vivo. D PPA is an inhibitory peptide of the PD-1/PD-L1 immune checkpoint pathway. The peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD-L1 reactivates effective immune responses to the tumors. In summary, the current study provides a new perspective on the regulation of tumor vessel normalization and immunotherapy based on functional peptide nanoparticles as nanomedicine for improved therapeutic purposes.

CD38 and MGluR1 as possible signaling molecules involved in epileptogenesis: A potential role for NAD+ homeostasis.

In spite of long-term intensive scientific research efforts, there are still many issues concerning the mechanisms of epileptogenesis and epilepsy to be resolved. Temporal lobe, in particular hippocampus, is vulnerable to epileptogenic process. Herein, electrical kindling model of temporal lobe were analyzed using proteomic approach. A dramatic decrease in nicotinamide adenine dinucleotide (NAD+) level was exhibited during the kindling procedure in hippocampus. After stage 3, high CD38 expression was detected by qPCR, nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) and western blot analysis. An increase in expression of CD38/NADase activity was observed during the kindling procedure in hippocampus that suggest it as one of the most important NAD+ degrading enzymes during epileptogenesis. Subsequently, gene expression of CD38 metabolite related proteins (Ryr2, FKBP-12.6, Chrm1, mGluR1 and Cnx43) were examined. Among them, changes in the expression level of mGluR1 was more than other genes, which was also confirmed by LC MS/MS and western blotting analysis. These findings provided valuable information about changes in the expression of CD38/cADPR signaling pathway and suggest its crucial role during epileptogenesis.

Cancer-associated-platelet-inspired nanomedicines for cancer therapy.

Platelets, with hemostasis and thrombosis activities, are one of the key components in the blood circulation. As a guard, they rapidly respond to any abnormal blood vessel injury signal and release their granules' contents, which induce their adhesion and aggregation on wound site for hemostasis. Recently, increasing evidence has indicated that platelets are critically involved in the growth and metastasis of cancer cells by releasing a variety of cytokines and chemokines to stimulate cancer cell proliferation and various angiogenic regulators to accelerate tumor angiogenesis. Platelets also secrete active transforming growth factor beta (TGF-ß) to promote the epithelial-mesenchymal transition of cancer cells and their extravasation from primary site, and form microthrombus on the surface of cancer cells to protect them from immune attack and high-speed shear force in the circulation. Therefore, blocking platelet-cancer cell interaction may be an attractive strategy to treat primary tumor and/or prevent cancer metastasis. However, systemic inhibition or depletion of platelets brings risk of severe bleeding complication. Cancer-associated-platelets-targeted nanomedicines and biomimetic nanomedicines coated with platelet membrane can be used for targeted anticancer drug delivery, due to their natural targeting ability to tumor cells and platelets. In the current review, we first summarized the platelet mechanisms of action in physiological condition and their multiple roles in cancer progression and conventional antiplatelet therapeutics. We then highlighted the recent progress on the design and fabrication of cancer-associated-platelet-targeted nanomedicines and platelet membrane coating nanomedicines for cancer therapy. Finally, we discussed opportunities and challenges and offered our thoughts for the future development. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures.

Covalent organic framework membrane for size selective release of small molecules and peptide in vitro.

The ability to control small drug release is crucial in biomedicine, especially for inhibiting the side effects of drugs, but it is still challenging. Herein, to mimic the controlled release of drugs, the release of organic molecules, e.g., small organic dyes and peptides, through Covalent Organic Framework (COF) membranes with ordered nanoscale pores has been investigated, showing constant zero-order release behaviours. Meanwhile, biological assessments show the good biocompatibility of the COF membrane-based release system, and the high stability of the COF membrane was manifested by the long-term release of small molecules in aqueous media.

Metastatic Small Cell Carcinoma Presenting as Acute Pancreatitis.

Small cell carcinoma is a malignant lung cancer with poor prognosis that occurs almost exclusively in heavy smokers. Small cell cancer typically arises from the central airways, with the most common presentation being a large hilar mass with bulky mediastinal adenopathy. Small cell lung cancer rarely metastasizes to pancreatic tissue and presents as acute pancreatitis. Here, we describe a case of metastatic small cell lung carcinoma initially presenting as acute pancreatitis. The patient underwent CT of the abdomen, magnetic resonance cholangiopancreatography, and endoscopic ultrasound with biopsy which confirmed the diagnosis of small cell lung carcinoma. After positron emission tomography staging, the patient was subsequently treated with radiotherapy in tandem with multiple cycles of cisplatin and etoposide with positive treatment response.

Pancreaticopleural Fistula: A Rare Presentation and a Rare Complication.

Pancreaticopleural fistula (PPF) is a rare complication of pancreatitis that requires a high index of clinical suspicion as patients typically present with pulmonary symptoms related to the pleural effusion rather than pancreatitis. Diagnosis is made by detection of amylase in the pleural fluid. Magnetic resonance cholangiopancreatography can aid in visualizing the fistula. We present a case of massive left pleural effusion secondary to a PPF due to acute on chronic pancreatitis.

Targeting Delivery of Platelets Inhibitor to Prevent Tumor Metastasis.

Activated platelets have a high affinity for tumor cells, and consequently, they can protect tumor cells from environmental stress and immune attacks. Therefore, preventing platelet-tumor cell interaction can lead to the elimination of circulating tumor cells via natural killer cells and finally metastasis inhibition. It is also shown that CREKA (Cys-Arg-Glu-Lys-Ala), a tumor-homing pentapeptide, targets fibrin-fibronectin complexes that are found on the tumor stroma and the vessel walls. In this study, we linked CREKA to Ticagrelor, a reversible antagonist of the P2Y12 receptor on platelets. In vitro experiments indicated that CREKA-Ticagrelor could not only inhibit the platelet-induced migration of tumor cells with an invasive phenotype but also prevent tumor-platelet interaction. In vivo antitumor and antimetastasis results of this drug showed that CREKA-Ticagrelor could specifically target the tumor tissues within 24 h post intravenous injection and suppress lung metastasis. Meanwhile, by having this antiplatelet drug targeted, its side effects were minimized, and bleeding risk was decreased. Thus, CREKA-Ticagrelor offers an efficient antimetastatic agent.

Dopamine Delivery via pH-Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs.

Tumor blood vessels have been reported to be abnormal in both structure and function compared with those in normal tissues, leading to a hostile microenvironment and inadequate antitumor drug delivery. Dopamine, a chemical messenger, is proven to inhibit angiogenesis and improve tumor vessel normalization. Here, a mesoporous silicon nanoparticle (MSN) is constructed that is responsive to the weakly acidic pH of the tumor extracellular matrix for steady delivery and tumor-localized release of dopamine. Then MSNs are functionalized with amine conjugated phenylboronicacid molecules, and dopamine is loaded by reacting with phenylboronic acid. In a weakly acidic environment, MSNs intelligently release dopamine due to the hydrolysis of boronic-ester bond between dopamine and phenylboronic acid, resulting in an evident inhibition of vascular endothelial cell migration and tubule formation. It is shown that loading of dopamine into the functional MSNs significantly prolong the circulatory half-life of this small molecule. After intravenous injection to tumor bearing mice, this nanoformulation induce tumor blood vessel normalization, thereby improving the antitumor chemotherapeutic efficacy of doxorubicin. This study demonstrates that the pH-responsive MSN offers great potential for delivery of dopamine in vivo and the normalization of tumor vessels by dopamine can provide an auxiliary treatment for cancer chemotherapeutic drugs.

Shortness of Breath: An Unusual Presentation of Bladder Injury. A Case Report and Literature Review of Urinothorax.

Urinothorax is the presence of urine in the pleural space. It can occur at any age and is more common in males. It typically results from obstructive uropathy but can also be caused by malignancy or trauma. Urinothorax is a rare cause of transudative pleural effusion and the only cause of low pH (pH <7.4) transudative effusion. We present the case of a 51-year-old female patient who had recently undergone a urological procedure and came to the emergency department reporting shortness of breath. A chest X-ray revealed a newly developed, large, right-sided pleural effusion. Thoracentesis yielded a transudative yellow fluid of normal pH with a creatinine-to-serum creatinine ratio of 1.7. A computed tomography (CT) cystogram showed extravasated contrast material within the pelvis, from which a diagnosis of urinothorax was confirmed and treated. Urinothorax is a rare diagnosis that requires a multidisciplinary treatment approach, usually including a pulmonologist and a urologist. After the genitourinary disease is treated, the urinothorax usually resolves.

Portal venous pressure as a predictor of mortality in cirrhotic patients undergoing emergency surgery.

OBJECTIVE: Emergency surgery is a risk factor for mortality in cirrhotic patients. Portal hypertension is an essential feature of decompensated cirrhosis. This study aimed to assess the value of portal venous pressure (PVP) measurement in prediction of 1-month mortality in cirrhotic patients undergoing emergency laparotomy. METHODS: This prospective study included 121 adults with liver cirrhosis subjected to an emergency laparotomy. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score were used for preoperative patient evaluation. PVP was measured directly at the beginning of surgery. Portal hypertension (PHT) is diagnosed when PVP is greater than 12 mmHg. The primary outcome measure was the risk of mortality within one month after surgery. RESULTS: PVP ranged from 5 to 27 mmHg; 82 patients (67.8%) had PHT. Fifty-five patients (45.5%) died within 1 month. Mortality was significantly associated with increasing CTP Class, MELD score and PHT (p < 0.001 for all). PHT predicts mortality with a sensitivity of 83.6% and specificity of 92.8%. PHT was the only independent predictor of mortality (OR: 23.0, 95%CI: 8.9-59.4). CONCLUSION: In patients with liver cirrhosis, emergency laparotomy carries a substantial risk of mortality within one month. Portal hypertension is an independent predictor of risk of mortality in these patients.

Isolated Polycystic Liver Disease: An Unusual Cause of Recurrent Variceal Bleed.

Isolated polycystic liver disease is a rare disorder. Majority of the patients with isolated polycystic liver disease are asymptomatic with incidental detection of liver cysts on imaging studies done for other purposes. Minority of patients develop symptoms which are mostly secondary to enlarging cysts size and hepatomegaly. Rarely, these patients develop portal hypertension and can present with its clinical manifestations and consequences in the form acute variceal bleeding or recurrent ascites. We present a rare case of 67-year-old female patient with significant history of polycystic liver disease who presented to the hospital with recurrent hematemesis and melena. She underwent esophagogastroduodenoscopy which showed multiple large esophageal varices requiring banding.

Sustained release of sodium deoxycholate from PLGA-PEG-PLGA thermosensitive polymer.

Delivery of the drugs to the target tissue and reducing their side effects on surrounding tissues is still a significant challenge for pharmaceutical scientists. The aim of this study was to investigate the suitability of PLGA-PEG-PLGA triblock copolymer as a matrix material for a sustained-release system of sodium deoxycholate (NaDC). The copolymer was synthesized by ring-opening polymerization reaction, using microwave irradiation and characterized by different techniques. It was shown that the introduction of NaDC to the PLGA-PEG-PLGA copolymer did not influence its inherent sol-gel transition behaviour, but increased the sol-gel transition. The results showed the appropriate NaDC/polymer interaction and the formation of NaDC/polymer-mixed micelle. The sustained release of NaDC from the copolymer lasted for 2 days. This release can be attributed to the formation of NaDC/polymer-mixed micelles and trapping NaDC in the copolymer matrix. The cytolytic efficacy of NaDC-loaded copolymer and sustained release of NaDC were investigated on human adipocytes. Overall a sustained-release formulation for NaDC can be used to study localized fat dissolution.

Recurrent Levamisole-Induced Agranulocytosis Complicated by Bowel Ischemia in a Cocaine User.

BACKGROUND Levamisole is a common adulterant of cocaine and up to 69% of seized cocaine in United States contains levamisole. It is a synthetic imidazothiazole derivative which was previously used as an immunomodulating agent for treatment of various connective tissue disorders and colorectal carcinoma. However, it was withdrawn later from the market due to significant toxicity associated with it. CASE REPORT We present the case of a 59-year-old male patient with a history of active cocaine use who presented to the hospital with febrile neutropenia and agranulocytosis. He underwent extensive work-up for neutropenia and was suspected to have it secondary to levamisole-adulterated cocaine. He was treated with antibiotics and granulocyte-stimulating factor. His white cell count improved and he was discharged home. He continued to use cocaine after discharge from the hospital. He returned to the hospital 3 weeks later with recurrent neutropenia and agranulocytosis complicated by septic shock and bowel necrosis which required prolonged antibiotics and a bowel resection. CONCLUSIONS Levamisole-induced agranulocytosis should be considered in patients who present with neutropenia and a history of cocaine use. Physicians should have high clinical suspicion and consider it a potential etiology of agranulocytosis when other causes have been excluded.

Surface Functionalization of Polymeric Nanoparticles with Umbilical Cord-Derived Mesenchymal Stem Cell Membrane for Tumor-Targeted Therapy.

Multiple cell plasma membranes have been utilized for surface functionalization of synthetic nanomaterials and construction of biomimetic drug delivery systems for cancer treatment. The natural characters and facile isolation of original cells facilitate the biomedical applications of plasma membranes in functionalizing nanocarriers. Human umbilical cord-derived mesenchymal stem cells (MSCs) have been identified to show tropism toward malignant lesions and have great advantages in ease of acquisition, low immunogenicity, and high proliferative ability. Here, we developed a poly(lactic- co-glycolic acid) (PLGA) nanoparticle with a layer of plasma membrane from umbilical cord MSC coating on the surface for tumor-targeted delivery of chemotherapy. Functionalization of MSC plasma membrane significantly enhanced the cellular uptake efficiency of PLGA nanoparticles, the tumor cell killing efficacy of PLGA-encapsulated doxorubicin, and most importantly the tumor-targeting and accumulation of the nanoparticles. As a result, this MSC-mimicking nanoformulation led to remarkable tumor growth inhibition and induced obvious apoptosis within tumor lesions. This study for the first time demonstrated the great potential of umbilical cord MSC plasma membranes in functionalizing nanocarriers with inherent tumor-homing features and the high feasibility of such biomimetic nanoformulations in cancer therapy.

Delivery of small interfering RNA against Nogo-B receptor via tumor-acidity responsive nanoparticles for tumor vessel normalization and metastasis suppression.

Nogo-B receptor (NgBR) plays fundamental roles in regulating angiogenesis, vascular development, and the epithelial-mesenchymal transition (EMT) of cancer cells. However, the therapeutic effect of NgBR blockade on tumor vasculature and malignancy is unknown, investigations on which requires an adequate delivery system for small interfering RNA against NgBR (NgBR siRNA). Here a surface charge switchable polymeric nanoparticle that was sensitive to the slightly acidic tumor microenvironment was developed for steady delivery of NgBR siRNA to tumor tissues. The nanoformulation was constructed by conjugating 2, 3-dimethylmaleic anhydride (DMMA) molecules to the surface amines of micelles formed by cationic co-polymer poly(lactic-co-glycolic acid)2-poly(ethylenimine) and subsequent absorption of NgBR siRNAs. The nanoparticles remained negatively charged in physiological condition and smartly converted to positive surface charge due to tumor-acidity-activated shedding of DMMA. The charge conversion facilitated cellular uptake of siRNAs and in turn efficiently depleted the expression of NgBR in tumor-bearing tissues. Silencing of NgBR suppressed endothelial cell migration and tubule formation, and reverted the EMT process of breast cancer cells. Delivery of the nanoformulation to mice bearing orthotopic breast carcinoma showed no effect on tumor growth, but led to remarkable decrease of distant metastasis by normalizing tumor vessels and suppressing the EMT of breast cancer cells. This study demonstrated that NgBR is a promising therapeutic target in abnormal tumor vasculature and aggressive cancer cells, and the tumor-responsive nanoparticle with the feature of charge transformation offers great potential for tumor-specific delivery of gene therapeutics.

Pyridostigmine Induced Prolonged Asystole in a Patient with Myasthenia Gravis Successfully Treated with Hyoscyamine.

Reversible acetylcholinesterase inhibitors are used as first-line treatment for myasthenia gravis. They improve symptoms by increasing concentration of acetylcholine at the neuromuscular junction and stimulating nicotinic receptors. Serious bradyarrhythmias can occur from muscarinic stimulation in heart, which in rare cases may progress to asystole. These patients can initially be managed with hyoscyamine, a muscarinic antagonist. Persistence of bradyarrhythmias even after hyoscyamine treatment may warrant pacemaker placement. We present a case of 65-year-old female patient who presented with diplopia, dysphagia, and muscle weakness who was diagnosed with myasthenia gravis. She developed significant sinoatrial node block with prolonged asystole after starting treatment with pyridostigmine which was successfully treated with hyoscyamine, thus avoiding pacemaker placement.