Malignant Hyperthermia.

OBJECTIVES: A narrative expert review aiming to summarize the clinical epidemiology and management of critically ill patients with malignant hyperthermia (MH). DATA SOURCES: Medline searches were conducted to identify relevant articles describing the epidemiology, pathophysiology, and management of MH. Guidelines from key MH organizations were also incorporated into this review. STUDY SELECTION: Relevant studies regarding MH in both ICU and perioperative settings were reviewed. DATA EXTRACTION: Data from relevant studies were summarized and qualitatively assessed. DATA SYNTHESIS: MH is a severe reaction triggered by inhalational volatile anesthetics and succinylcholine in genetically susceptible patients. The condition is characterized by an early onset (min to hr) rise in temperature, hypercarbia, and muscular rigidity following exposure to triggering medications with potential complications of coagulopathy, rhabdomyolysis, and acute kidney injury. Acute management necessitates a coordinated multidisciplinary team approach with specific management using dantrolene, active cooling, and hyperventilation. A suspected MH reaction has important implications for future anesthetic exposure for both the patient and their family. All suspected reactions should be followed up at a specialized MH testing center using muscle contracture and genetic testing. CONCLUSIONS: Increasing use of inhalational anesthetics in the ICU underscores the need for enhanced education on the diagnosis and management of MH to ensure optimal patient sedation care and safety.

Myopathic manifestations across the adult lifespan of patients with malignant hyperthermia susceptibility: a narrative review.

Malignant hyperthermia susceptibility (MHS) designates individuals at risk of developing a hypermetabolic reaction triggered by halogenated anaesthetics or the depolarising neuromuscular blocking agent suxamethonium. Over the past few decades, beyond the operating theatre, myopathic manifestations impacting daily life are increasingly recognised as a prevalent phenomenon in MHS patients. At the request of the European Malignant Hyperthermia Group, we reviewed the literature and gathered the opinion of experts to define MHS-related myopathy as a distinct phenotype expressed across the adult lifespan of MHS patients unrelated to anaesthetic exposure; this serves to raise awareness about non-anaesthetic manifestations, potential therapies, and management of MHS-related myopathy. We focused on the clinical presentation, biochemical and histopathological findings, and the impact on patient well-being. The spectrum of symptoms of MHS-related myopathy encompasses muscle cramps, stiffness, myalgias, rhabdomyolysis, and weakness, with a wide age range of onset mainly during adulthood. Histopathological analysis can reveal nonspecific abnormalities suggestive of RYR1 involvement, while metabolic profiling reflects altered energy metabolism in MHS muscle. Myopathic manifestations can significantly impact patient quality of life and lead to functional limitations and socio-economic burden. While currently available therapies can provide symptomatic relief, there is a need for further research into targeted treatments addressing the underlying pathophysiology. Counselling early after establishing the MHS diagnosis, followed by multidisciplinary management involving various medical specialties, is crucial to optimise patient care.

Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer.

Importance: The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed. Objective: To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC. Design, Setting, and Participants: This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the primary measurement period to verify performance rates, specify a potential measure, and test for validity, reliability, and feasibility. The Optum Labs Data Warehouse (OLDW), a deidentified database of health care claims and clinical data, was accessed. The OLDW contains longitudinal health information on enrollees and patients, representing a diverse mixture of ages and geographic regions across the US. For the database study, adults from 38 health care organizations (HCOs) aged 50 to 75 years who completed an initial CRC SBT with an abnormal result were observed to determine follow-up colonoscopy rates within 6 months. Rates were stratified by race, ethnicity, sex, insurance, and test modality. Three HCOs participated in the feasibility field testing. Data were analyzed from June 1, 2022, to May 31, 2023. Main Outcome and Measures: The primary outcome consisted of follow-up colonoscopy rates following an abnormal SBT result for CRC. Reliability statistics were also calculated across HCOs, race, ethnicity, and measurement year. Results: Among 20 581 adults (48.6% men and 51.4% women; 307 [1.5%] Asian, 492 [7.2%] Black, 644 [3.1%] Hispanic, and 17 705 [86.0%] White; mean [SD] age, 63.6 [7.1] years) in 38 health systems, 47.9% had a follow-up colonoscopy following an abnormal SBT result for CRC within 6 months. There was significant variation between HCOs. Notably, significantly fewer Black patients (37.1% [95% CI, 34.6%-39.5%]) and patients with Medicare (49.2% [95% CI, 47.7%-50.6%]) or Medicaid (39.2% [95% CI, 36.3%-42.1%]) insurance received a follow-up colonoscopy. A quality performance measure that tracks rates of follow-up within 6 months of an abnormal SBT result was observed to be feasible, valid, and reliable, with a median reliability statistic between HCOs of 94.5% (range, 74.3%-99.7%). Conclusions and Relevance: The findings of this observational study of 20 581 adults suggest that a measure of follow-up colonoscopy within defined periods after an abnormal result of an SBT test for CRC is warranted based on low current performance rates and would be feasible to collect by health systems and produce valid, reliable results.

Uncoupling cytosolic calcium from membrane voltage by transient receptor potential melastatin 4 channel (TRPM4) modulation: A novel strategy to treat ventricular arrhythmias.

The current antiarrhythmic paradigm is mainly centered around modulating membrane voltage. However, abnormal cytosolic calcium (Ca2+) signaling, which plays an important role in driving membrane voltage, has not been targeted for therapeutic purposes in arrhythmogenesis. There is clear evidence for bidirectional coupling between membrane voltage and intracellular Ca2+. Cytosolic Ca2+ regulates membrane voltage through Ca2+-sensitive membrane currents. As a component of Ca2+-sensitive currents, Ca2+-activated nonspecific cationic current through the TRPM4 (transient receptor potential melastatin 4) channel plays a significant role in Ca2+-driven changes in membrane electrophysiology. In myopathic and ischemic ventricles, upregulation and/or enhanced activity of this current is associated with the generation of afterdepolarization (both early and delayed), reduction of repolarization reserve, and increased propensity to ventricular arrhythmias. In this review, we describe a novel concept for the management of ventricular arrhythmias in the remodeled ventricle based on mechanistic concepts from experimental studies, by uncoupling the Ca2+-induced changes in membrane voltage by inhibition of this TRPM4-mediated current.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review. / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por V. cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Reportamos un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa (PCR) y test de aglutinación. Se describen además las características clínico-epidemiológicas y opciones terapéuticas para esta infección.

Optimizing neuromuscular blockade management for improving patient safety and peri-operative outcomes: a pilot phase of a quality improvement initiative.

INTRODUCTION: Although quantitative monitoring of neuromuscular blockade (NMB) is recommended, it is not routinely used in daily practice. The optimizing NMB management to improve patient safety and perioperative outcomes (OBISPO) quality improvement (QI) initiative intends to address this issue and change clinicians' behaviors. MATERIAL AND METHODS: A pilot phase of the prospective QI intervention was conducted. The primary objective was implement clinical practice change that emphasizes improving NMB monitoring in patients undergoing elective cardiac surgery who are eligible for fast-track extubation between February 2021 and December 2021. The secondary objective was to reduce the train-of-four ratio (TOFR) < 0.9 incidence before tracheal extubation to less than 20%. The intervention included educational sessions for teams. RESULTS: A total of 859 patients underwent elective cardiac surgery, 40% were eligible for fast-track extubation. From our cohort of fast-track cardiac cases, 69% had reported TOFR; 47% of them had residual paralysis (TOFR < 0.9) on arrival to PACU, 22% persisted with residual paralysis after extubation, and 27% were extubated without monitoring. The survey identified cognitive biases, knowledge gaps, unfamiliarity, and lack of trust in quantitative monitoring devices. Workflow disruptions imposed by COVID and changes in NMB monitoring devices have negatively affected our initiative. CONCLUSIONS: Our study showed that changes in clinician behavior are among the most challenging issues in perioperative medicine. Continuous teaching and QI initiatives, focused on quantitative NMB monitors and adequate reversal agent use, are mandatory to improve perioperative outcomes. Therefore, new proposals are required to promote changes in current practices.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por Vibrio cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Se reporta un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa y test de aglutinación. Se describen las características clinicoepidemiológicas y las opciones terapéuticas para esta infección.

Clinical and epidemiological characteristics of mpox: A descriptive cases series in Colombia.

INTRODUCTION: Colombia is the fifth most affected country by the global monkeypox outbreak and the second in LAC after Brazil. We describe the clinical and epidemiological characteristics of 521 patients with mpox in the country. METHODS: We conducted an observational analysis of laboratory-confirmed Mpox cases between June 29 and November 16, 2022. RESULTS: Most cases were young men living with HIV. The clinical evolution was primarily benign, with two deaths reported. We found some differences between women and men regarding their BMI, presence of lymphadenopathies, localization of lesions, and the antecedent of HIV infection. CONCLUSION: Although it seems that the epidemic curve for this outbreak of Mpox is decreasing not only in Colombia but globally, it could remain endemic. Therefore, it is necessary to maintain very close surveillance.

Fungemia in Hospitalized Adult Patients with Hematological Malignancies: Epidemiology and Risk Factors.

Fungemia in hematologic malignancies (HM) has high mortality. This is a retrospective cohort of adult patients with HM and fungemia between 2012 and 2019 in institutions of Bogotá, Colombia. The epidemiological, clinical, and microbiological characteristics are described, and risk factors related to mortality are analyzed. One hundred five patients with a mean age of 48 years (SD 19.0) were identified, 45% with acute leukemia and 37% with lymphomas. In 42%, the HM was relapsed/refractory, 82% ECOG > 3, and 35% received antifungal prophylaxis; 57% were in neutropenia, with an average duration of 21.8 days. In 86 (82%) patients, Candida spp. was identified, and other yeasts in 18%. The most frequent of the isolates were non-albicans Candida (61%), C. tropicalis (28%), C. parapsilosis (17%), and C. krusei (12%). The overall 30-day mortality was 50%. The survival probability at day 30 in patients with leukemia vs. lymphoma/multiple myeloma (MM0 group was 59% (95% CI 46-76) and 41% (95% CI 29-58), p = 0.03, respectively. Patients with lymphoma or MM (HR 1.72; 95% CI 0.58-2.03) and ICU admission (HR 3.08; 95% CI 1.12-3.74) were associated with mortality. In conclusion, in patients with HM, non-albicans Candida species are the most frequent, and high mortality was identified; moreover, lymphoma or MM and ICU admission were predictors of mortality.

The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?

Candida auris has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.7%) and 52 controls (C. albicans, 21.6%; C. parapsilosis, 21.6%; C. tropicalis, 21.6%; C. glabrata, 1.4%) were included and analysed in this study. Risk factors, clinical and microbiological characteristics and outcomes of patients with C. auris and non-auris Candida species (NACS) candidemia were compared. Previous fluconazole exposure was significantly higher in C. auris candidemia patients (OR 3.3; 1.15-9.5). Most C. auris isolates were resistant to fluconazole (86.3%) and amphotericin B (59%) whilst NACS isolates were generally susceptible. No isolates resistant to echinocandins were detected. The average time to start antifungal therapy was 3.6 days. Sixty-three (85.1%) patients received adequate antifungal therapy, without significant differences between the two groups. The crude mortality at 30 and 90 days of candidemia was up to 37.8% and 40.5%, respectively. However, there was no difference in mortality both at 30 and 90 days between the group with candidemia by C. auris (31.8%) and by NACS (42.3%) (OR 0.6; 95% IC 0.24-1.97) and 36.4% and 42.3% (0.77; 0.27-2.1), respectively. In this study, mortality due to candidemia between C. auris and NACS was similar. Appropriate antifungal therapy in both groups may have contributed to finding no differences in outcomes.

Dynamics of Anti-influenza Mucosal IgA Over a Season in a Cohort of Individuals Living or Working in a Long-term Care Facility.

BACKGROUND: Serological surveys are used to ascertain influenza infection and immunity, but evidence for the utility of mucosal immunoglobulin A (IgA) as a correlate of infection or protection is limited. METHODS: We performed influenza-like illness (ILI) surveillance on 220 individuals living or working in a retirement community in Gainesville, Florida from January to May 2018, and took pre- and postseason nasal samples of 11 individuals with polymerase chain reaction (PCR)-confirmed influenza infection and 60 randomly selected controls. Mucosal IgA against 10 strains of influenza was measured from nasal samples. RESULTS: Overall, 28.2% and 11.3% of individuals experienced a 2-fold and 4-fold rise, respectively, in mucosal IgA to at least 1 influenza strain. Individuals with PCR-confirmed influenza A had significantly lower levels of preseason IgA to influenza A. Influenza-associated respiratory illness was associated with a higher rise in mucosal IgA to influenza strains of the same subtype, and H3N2-associated respiratory illness was associated with a higher rise in mucosal IgA to other influenza A strains. CONCLUSIONS: By comparing individuals with and without influenza illness, we demonstrated that mucosal IgA is a correlate of influenza infection. There was evidence for cross-reactivity in mucosal IgA across influenza A subtypes.

Distinct pathophysiological characteristics in developing muscle from patients susceptible to malignant hyperthermia.

BACKGROUND: Most patients with malignant hyperthermia susceptibility diagnosed by the in vitro caffeine-halothane contracture test (CHCT) develop excessive force in response to halothane but not caffeine (halothane-hypersensitive). Hallmarks of halothane-hypersensitive patients include high incidence of musculoskeletal symptoms at rest and abnormal calcium events in muscle. By measuring sensitivity to halothane of myotubes and extending clinical observations and cell-level studies to a large group of patients, we reach new insights into the pathological mechanism of malignant hyperthermia susceptibility. METHODS: Patients with malignant hyperthermia susceptibility were classified into subgroups HH and HS (positive to halothane only and positive to both caffeine and halothane). The effects on [Ca2+]cyto of halothane concentrations between 0.5 and 3 % were measured in myotubes and compared with CHCT responses of muscle. A clinical index that summarises patient symptoms was determined for 67 patients, together with a calcium index summarising resting [Ca2+]cyto and spontaneous and electrically evoked Ca2+ events in their primary myotubes. RESULTS: Halothane-hypersensitive myotubes showed a higher response to halothane 0.5% than the caffeine-halothane hypersensitive myotubes (P<0.001), but a lower response to higher concentrations, comparable with that used in the CHCT (P=0.055). The HH group had a higher calcium index (P<0.001), but their clinical index was not significantly elevated vs the HS. Principal component analysis identified electrically evoked Ca2+ spikes and resting [Ca2+]cyto as the strongest variables for separation of subgroups. CONCLUSIONS: Enhanced sensitivity to depolarisation and to halothane appear to be the primary, mutually reinforcing and phenotype-defining defects of halothane-hypersensitive patients with malignant hyperthermia susceptibility.

Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia-Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability.

BACKGROUND: Patients susceptible to malignant hyperthermia (MH) may experience disabling manifestations of an unspecified myopathy outside the context of anesthesia, including myalgia, fatigue, or episodic rhabdomyolysis. Clinical observations suggest that oral dantrolene may relief myopathic symptoms in MH-susceptible (MHS) patients. However, high-dose oral dantrolene has been associated with severe hepatotoxicity. METHODS: In a retrospective database review (1994-2018), we investigated a cohort of patients who were diagnosed as MHS by a positive caffeine-halothane contracture test (CHCT), had myopathic manifestations, and received oral dantrolene. Our aim was to investigate the occurrence of serious adverse effects and the adherence to oral dantrolene therapy. We also explored factors associated with self-reported clinical improvement, considering as nonresponders patients with intolerable adverse effects or who reported no improvement 8 weeks after starting treatment. RESULTS: Among 476 MHS patients with positive CHCT, 193 had muscle symptoms, 164 started oral dantrolene, 27 refused treatment, and 2 were excluded due to abnormal liver function before starting therapy. There were no serious adverse effects reported. Forty-six of 164 patients (28%; 95% confidence interval [CI], 22%-35%) experienced mild to moderate adverse effects. Twenty-two patients (22/164, 13%; 95% CI, 9%-19%) discontinued treatment, among which 16 due to adverse effects and 6 due to lack of improvement. One hundred forty-two patients (87%; 95% CI, 80%-90%) adhered to therapy and reported improvement of myalgia (n = 78), fatigue (n = 32), or rhabdomyolysis/hiperCKemia (n = 32). The proportion of responders was larger among patients with MH history than among those referred due to a clinical myopathy with nonpertinent anesthetic history (97% vs 79%, respectively; 95% CI of the difference, 8.5-28; P < .001). Patients with a sarcoplasmic reticulum Ca2+ release channel ryanodine receptor gene ( RYR1 ) variant had higher odds of responding to dantrolene treatment (OR, 6.4; 95% CI, 1.3-30.9; P = .013). Dantrolene median dose was 50 (25-400) and 200 (25-400) mg·day -1 in responders and nonresponders, respectively. CONCLUSIONS: We found that oral dantrolene produced no serious adverse effects within the reported dose range, and was well tolerated by most MH-susceptible patients presenting myopathic symptoms. Our study provides dosing and adverse effect data as a basis for further randomized controlled clinical trials to determine the efficacy of oral dantrolene for symptomatic relief in MHS-related myopathies.

Experimental intoxication of Brahman (Bos indicus) heifers with Enterolobium cyclocarpum fruits.

Enterolobium cyclocarpum is a poisonous plant distributed throughout the Americas. The E. cyclocarpum fruits have high toxic potential for cattle in Colombia and the clinical signs and pathological lesions are ill-defined. To begin address this issue, twelve Brahman heifers were administered E. cyclocarpum fruits and the evolution of clinical signs were recorded. Blood was collected to establish biochemical and hematological parameters. Animals were euthanized between 4 and 15 days after the initial dose was given, and tissue samples were routinely processed and stained by Hematoxylin-Eosin. The severity of clinical signs and tissue lesions were correlated with the dose of E. cyclocarpum fruits. Clinical signs included fever, tachypnea, sialorrhea, jaundice, tympanism, and diarrhea. Skin lesions were consistent with photosensitization. Hematological and biochemical tests showed increased hematocrit, neutropenia, increased serum fibrinogen, elevated hepatic enzymes and azotemia. Histology revealed panlobular cytoplasmic vacuolization and extensive foci of necrosis in the liver. The skin, fore-stomach, abomasum and intestine revealed microcirculatory, inflammatory and ulcerative changes. Protein casts and tubular epithelium vacuolization were found in kidney. Depending on the toxicosis intensity, it is concluded that E. cyclocarpum fruits may cause two clinical and pathological forms of poisoning in Brahman heifers. First, a severe intoxication at repeated exposition with high (20 g/kg/d) or low (10 g/kg/d) dose that affected the digestive and tegumentary systems and the kidney. Second, a mild to moderate form with a single low dose (10 g/kg/d) that affected in lower grades the same systems/organs.

Impact of SARS-CoV-2 vaccination in healthcare workers in a network of clinics in Latin America.

Objectives: Healthcare workers (HCWs) have been severely affected in terms of both morbidity and mortality since the beginning of the COVID-19 pandemic. During the first few months of 2021, Colombia experienced a surge in positive cases. This study aimed to evaluate the effect of vaccination on the incidence of new positive cases in HCWs. Design: This was a retrospective cohort study of frontline employees in a network of clinics in Colombia, who were prioritized for COVID-19 vaccination from February to March 2021. Results: Our findings were consistent with recent reports. During early 2020, the incidence of HCWs positively diagnosed with COVID-19 in Colombia was higher than that for the general population. With the start of the national vaccination program, the incidence among HCWs decreased from April 2021, while that for the general population remained relatively unchanged. Our study identified lower infection rates among HCWs during April (odds ratio [OR], 0.72 [95% CI 0.58-0.90]; p < 0.01) and May (odds ratio [OR], 0.25 [95% CI 0.18-0.36]; p < 0.01). Conclusions: COVID-19 vaccination rollout in Colombia during early 2021 led to a decrease in the incidence of new positive cases among HCWs, in contrast to a continuing surge in the general population. Our findings suggested that COVID-19 vaccination provided adequate immunity, which guaranteed protection to HCWs.