RESUMEN
We previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The platform design was based on the use of clinical antibodies as scaffolds into which replicated natural complementarity-determining regions purged of sequence liabilities were inserted, and the use of phage and yeast display to carry out antibody selection. In addition to being developable, antibodies generated using our platform were extremely diverse, with most campaigns yielding sub-nanomolar binders. Here, we describe a platform advancement that incorporates Fab phage display followed by single-chain antibody-binding fragment Fab (scFab) yeast display. The scFab single-gene format provides balanced expression of light and heavy chains, with enhanced conversion to IgG, thereby combining the advantages of scFvs and Fabs. A meticulously engineered, quality-controlled Fab phage library was created using design principles similar to those used to create the scFv library. A diverse panel of binding scFabs, with high conversion efficiency to IgG, was isolated against two targets. This study highlights the compatibility of phage and yeast display with a Fab semi-synthetic library design, offering an efficient approach to generate drug-like antibodies directly, facilitating their conversion to potential therapeutic candidates.
Asunto(s)
Afinidad de Anticuerpos , Fragmentos Fab de Inmunoglobulinas , Biblioteca de Péptidos , Anticuerpos de Cadena Única , Fragmentos Fab de Inmunoglobulinas/genética , Fragmentos Fab de Inmunoglobulinas/inmunología , Fragmentos Fab de Inmunoglobulinas/química , Humanos , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/inmunología , Anticuerpos de Cadena Única/química , Afinidad de Anticuerpos/inmunología , Técnicas de Visualización de Superficie Celular/métodos , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Inmunoglobulina G/químicaRESUMEN
Mammalian Ste-20-like Kinases 1 and 2 (MST1/2) are core serine-threonine kinases of the Hippo pathway regulating several cellular processes, including cell cycle arrest and cell death. Here, we discovered a novel alternative splicing variant of the MST2 encoding gene, STK3, in malignant cells and tumor datasets. This variant, named STK3∆7 or MST2∆7 (for mRNA or protein, respectively), resulted from the skipping of exon 7. MST2∆7 exhibited increased ubiquitylation and interaction with the E3 ubiquitin-protein ligase CHIP compared to the full-length protein (MST2FL). Exon 7 in STK3 encodes a segment within the kinase domain, and its exclusion compromised MST2 interaction with and phosphorylation of MOB, a major MST1/2 substrate. Nevertheless, MST2∆7 was capable of interacting with MST1 and MST2FL. Unlike MST2FL, overexpression of MST2∆7 did not lead to increased cell death and growth arrest. Strikingly, we observed the exclusion of STK3 exon 7 in 3.2-15% of tumor samples from patients of several types of cancer, while STK3∆7 was seldomly found in healthy tissues. Our study identified a novel STK3 splicing variant with loss of function and the potential to disturb tissue homeostasis by impacting on MST2 activities in the regulation of cell death and quiescence.
RESUMEN
BACKGROUND: The sleeve gastrectomy (SG) has become the most common bariatric procedure worldwide. However, insufficient weight loss or weight recidivism is frequent, which may require effective and safe revisional procedures. OBJECTIVE: To determine the technical feasibility and safety of a minimally invasive, duodeno-ileal side-to-side anastomosis using a Sutureless Neodymium Anastomosis Procedure (SNAP) for patients with weight recidivism or inadequate weight loss following SG. METHODS: This is a prospective, single-arm, open-label pilot study that enrolled patients with obesity to assist in weight reduction following an SG performed > 12 months prior. For the SNAP, self-assembling magnets were deployed into the ileum (laparoscopically) and duodenum (per-oral endoscopy). Magnets were coupled under laparoscopic and fluoroscopic guidance to create a compression anastomosis. The primary endpoints were technical feasibility, weight loss, and rate of serious adverse events (SAEs). RESULTS: Successful duodeno-ileal diversions were created with SNAP in 27 participants (mean age: 50.6 ± 9.1, mean BMI: 38.1 ± 4.6 kg/m2) with no device-related serious adverse events. Upper endoscopy at 3 months confirmed patent, healthy anastomoses in all patients. At 9 months, patients (n = 24) experienced 11.9 ± 6.2%, 14.5 ± 10.8%, and 17.0 ± 13.9% TBWL at 3, 6, and 9 months, respectively. There were no device-related SAEs. CONCLUSION: The SNAP is technically feasible and relatively safe, with all patients presenting widely patent anastomosis at 3 months. Patients experienced a progressive, clinically meaningful weight loss. Further studies are needed to confirm our findings.
Asunto(s)
Anastomosis Quirúrgica , Duodeno , Estudios de Factibilidad , Gastrectomía , Pérdida de Peso , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proyectos Piloto , Gastrectomía/métodos , Anastomosis Quirúrgica/métodos , Duodeno/cirugía , Adulto , Neodimio , Obesidad Mórbida/cirugía , Íleon/cirugía , Cirugía Bariátrica/métodos , Resultado del Tratamiento , Laparoscopía/métodosRESUMEN
Background/Aim: The parotid is the largest salivary gland and is located anteriorly to the sternocleidomastoid muscle and laterally to the ramus of the mandible. Neoplasms in this gland are relatively rare, with 80% being benign and 20% malignant, primarily represented by mucoepidermoid carcinoma. In the head and neck region, lymphoepithelial carcinoma (LEC) accounts for 0.4% of malignant salivary gland tumors. Case Report: A 35-year-old man with no previous comorbidities was admitted to a Head and Neck Surgery Specialty Service for a painless right cervical mass of uncertain growth. Extensive diagnostic investigation revealed involvement of the contralateral parotid, associated with systemic lymph node enlargement. Thus, adjuvant radiotherapy was decided by the treating team. Conclusion: This case confirms the heterogeneous features and distinctive behavior that the disease can present, as seen with bilateral parotid LEC.
RESUMEN
BACKGROUND: Roux-en-Y gastric bypass (RYGB) has consistently demonstrated excellent weight loss and comorbidity resolution. However, outcomes vary based on patient's BMI. Single anastomosis duodeno-ileostomy with sleeve (SADI-S) is a novel procedure with promising short-term results. The long-term outcomes of SADI-S in patients with BMI ≥ 50 kg/m2 are not well described. We aim to compare the safety and efficacy of SADI-S with RYGB in this patient population. METHODS: We performed a multicenter retrospective study of patients with a BMI ≥ 50 kg/m2 who underwent RYGB or SADI-S between 2008 and 2023. Patient demographics, peri- and post-operative characteristics were collected. Complication rates were reported at 6, 12, 24, and 60 months postoperatively. A multivariate linear regression was used to evaluate and compare weight loss outcomes between both procedures. RESULTS: A total of 968 patients (343 RYGB and 625 SADI-S; 68.3% female, age 42.9 ± 12.1 years; BMI 57.3 ± 6.7 kg/m2) with a mean follow-up of 3.6 ± 3.6 years were included. Patients who underwent RYGB were older, more likely to be female, and have a higher rate of sleep apnea (p < 0.001), hypertension (p = 0.015), dyslipidemia (p < 0.001), and type 2 diabetes (p = 0.016) at baseline. The rate of bariatric surgery-specific complications was lower after SADI-S compared to RYGB. We reported no bariatric surgery related deaths after 1 year following both procedures. SADI-S demonstrated statistically higher and sustained weight loss at each time interval compared to RYGB (p < 0.001) even after controlling for multiple confounders. Lastly, the rate of surgical non-responders was lower in the SADI-S cohort. CONCLUSIONS: In our cohort, SADI-S was associated with higher and sustained weight-loss results compared to RYGB. Comorbidity resolution was also higher after SADI-S. Both procedures demonstrate a similar safety profile. Further studies are required to validate the long-term safety of SADI-S compared to other bariatric procedures.
Asunto(s)
Índice de Masa Corporal , Derivación Gástrica , Obesidad Mórbida , Pérdida de Peso , Humanos , Femenino , Masculino , Derivación Gástrica/métodos , Derivación Gástrica/efectos adversos , Estudios Retrospectivos , Adulto , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Persona de Mediana Edad , Duodeno/cirugía , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anastomosis Quirúrgica/métodosRESUMEN
BACKGROUND: Obesity is a well-known risk factor for gastroesophageal reflux disease (GERD). Even though symptoms may be mitigated or resolved with the weight loss caused by sleeve gastrectomy (SG), it may be associated with higher incidences of postoperative GERD. Ligamentum teres cardiopexy (LTC) is an alternative to Roux-en-Y gastric bypass, the gold standard treatment for GERD. METHODS: This study was a retrospective single-center chart review, all patients in this cohort underwent LTC to treat refractory GERD at our institution. The option for LTC was presented after patients' refusal to undergo RYGB conversion. We collected baseline characteristics, standard demographics, pre-operative tests and imaging, and SG information, as well as intraoperative and perioperative data regarding LTC, and postoperative complications. RESULTS: Our cohort included 29 patients; most were Caucasian (44.8%) females (86.2%). The mean weight and BMI before LTC were 216.5 ± 39.3 lb and 36.1 ± 5.4 kg/m2, respectively. Mean total body-weight loss (TBWL) at 12 and 24 months were 28.7% ± 9.5% and 28.4% ± 12.4%, respectively. The mean interval between the index bariatric surgery and LTC was 59.9 ± 34.9 months, mean operative time was 67 ± 18.2 min, and median length of stay (LOS) was 1 day (IQR = 1-2 days). Twelve patients (57.1%) were able to discontinue antisecretory medications, while 9 (42.9%) still required them to remain asymptomatic. Mortality and reoperation rates were 0% and the incidence of complication was 19.4% (n = 6). CONCLUSIONS: LTC is a safe and effective surgical alternative to treat refractory GERD symptoms after SG.
Asunto(s)
Derivación Gástrica , Reflujo Gastroesofágico , Laparoscopía , Obesidad Mórbida , Ligamentos Redondos , Femenino , Humanos , Masculino , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Reflujo Gastroesofágico/etiología , Derivación Gástrica/métodos , Laparoscopía/métodos , Reoperación/métodos , Gastrectomía/métodos , Ligamentos Redondos/cirugía , Pérdida de Peso , Resultado del TratamientoRESUMEN
Microneurographic recordings of muscle sympathetic nerve activity (MSNA) and the succeeding changes in beat-to-beat blood pressure (i.e., sympathetic transduction) provide important insights into the neural control of the circulation in humans. Despite its widespread use, the reliability of this technique remains unknown. Herein, we assessed the intra- and interday test-retest reliability of signal-averaging sympathetic transduction to blood pressure. Data were analyzed from 15 (9 M/6 F) young, healthy participants who completed two baseline recordings of fibular nerve MSNA separated by 60 min (intraday). The interday reliability was obtained in a subset of participants (n = 13, 9 M/4 F) who completed a follow-up MSNA study. Signal-averaging sympathetic transduction was quantified as peak change in diastolic (DBP) and mean arterial pressure (MAP) following a burst of MSNA. Analyses were also computed considering different MSNA burst sizes (quartiles of normalized MSNA) and burst patterns (singlets, couplets, triplets, and quadruplets+), as well as nonburst responses. Intraclass-correlation coefficients (ICCs) were used as the main reliability measure. Peak changes in MAP [intraday: ICC = 0.76 (0.30-0.92), P = 0.006; interday: ICC = 0.91 (0.63-0.97), P < 0.001] demonstrated very good to excellent reliability. Sympathetic transduction of MSNA burst size displayed moderate to very good reliability, though the reliability of MSNA burst pattern was poor to very good. Nonburst responses revealed poor intraday [ICC = 0.37 (-1.05 to 0.80), P = 0.21], but very good interday [ICC = 0.76 (0.18-0.93), P = 0.01] reliability. Intraday reliability measures were consistently lower than interday reliability. Similar results were obtained using DBP. Collectively, these findings provide evidence that the burst-triggering signal-averaging technique is a reliable measure of sympathetic transduction to blood pressure in young, healthy adults.NEW & NOTEWORTHY We found that signal-averaging sympathetic transduction to blood pressure displayed very good to excellent intra- and interday test-retest reliability in healthy, young adults. Reliability analyses according to muscle sympathetic burst size, burst pattern, and nonburst response were less consistent. Results were similar when using diastolic or mean arterial pressure in the transduction calculation. These findings suggest that the signal-averaging technique can be used with confidence to investigate sympathetic transduction to blood pressure in humans across time.
Asunto(s)
Músculo Esquelético , Sistema Nervioso Simpático , Adulto Joven , Humanos , Presión Sanguínea/fisiología , Reproducibilidad de los Resultados , Músculo Esquelético/fisiología , Sistema Nervioso Simpático/fisiología , Frecuencia Cardíaca/fisiologíaRESUMEN
Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite's biological complexity. In this study, we utilized the innovative phage-display immunoprecipitation followed by a sequencing approach (PhIP-Seq) to screen the immune response of 10 infected rhesus macaques during self-cure and challenge-resistant phases, identifying vaccine candidates. Our high-throughput S. mansoni synthetic DNA phage-display library encoded 99.6% of 119,747 58-mer peptides, providing comprehensive coverage of the parasite's proteome. Library screening with rhesus macaques' antibodies, from the early phase of establishment of parasite infection, identified significantly enriched epitopes of parasite extracellular proteins known to be expressed in the digestive tract, shifting towards intracellular proteins during the late phase of parasite clearance. Immunization of mice with a selected pool of PhIP-Seq-enriched phage-displayed peptides from MEG proteins, cathepsins B, and asparaginyl endopeptidase significantly reduced worm burden in a vaccination assay. These findings enhance our understanding of parasite-host immune responses and provide promising prospects for developing an effective schistosomiasis vaccine.
RESUMEN
BACKGROUND: Physiology is widely recognized as a difficult course, which can potentially increase students' withdrawal and failures rates. Several factors are likely contributing to the difficulties in learning physiology, including inherent features of the discipline as well as aspects related to instructions and/or students' perception. With regards to the later, it is currently unknown how students of exercise physiology think and explain physiology in terms of its cause or consequence (i.e., teleological or mechanistic thinking). Therefore, the aims of the present study were to determine 1) whether undergraduate students' perception of cardiorespiratory physiology during exercise follows a predominant teleological or mechanistic thinking, and 2) whether prior enrollment in physiology courses can influence the predominance of teleological vs. mechanistic thinking. METHODS: The test instrument was an online questionnaire about exercise physiology consisting of nine incomplete sentences about exercise physiology where students had to choose between a teleological or a mechanistic complement. The questionnaire was administered to undergraduate students in the following areas: 1) Movement Sciences (n = 152), 2) Health-related (n = 81) and, 3) Health-unrelated programs (n = 64). Students in Movement Sciences and Health-related programs were also analyzed separately in the following categories: 1) students who previously undertook physiology courses, and 2) students who did not take physiology courses. RESULTS: Overall, all groups presented a percentage of teleological thinking above 58%, which is considerably high. Teleological thinking was significantly higher in health-unrelated programs than health-related and movement sciences programs (76 ± 16% vs. 58 ± 26% vs. 61 ± 25%; P < 0.01). Further, students with prior enrollment in physiology classes presented a significantly lower percentage of teleological thinking than students without physiology classes (59 ± 25% vs. 72 ± 22%, respectively; P < 0.01), but the overall teleological reasoning remained predominant. CONCLUSIONS: These results confirm the hypothesis that undergraduate students tend to present teleological as opposed to mechanistic thinking in exercise physiology. Furthermore, although undergraduate students with prior enrollment in physiology classes presented significantly lower teleological thinking, it remained highly predominant suggesting that teleological thinking is partially independent of the degree of familiarity with this discipline.
Asunto(s)
Fisiología , Estudiantes , Humanos , Aprendizaje , Solución de Problemas , Percepción , Fisiología/educaciónRESUMEN
Targeted therapies have increased cancer therapy-related diarrhea (CTD) burden, with high incidence and/or severity of diarrhea for some agents that inhibit epidermal growth factor receptor and receptor tyrosine kinases. Neratinib is a pan-HER tyrosine kinase inhibitor approved for breast cancer treatment and causes severe diarrhea in >95% of patients. Crofelemer, a novel intestinal chloride ion channel modulator, is an approved antidiarrheal drug for symptomatic relief of noninfectious diarrhea in patients with HIV/AIDS receiving antiretroviral therapy. The objective of this study was to evaluate the effectiveness of crofelemer prophylaxis in reducing the incidence /severity of neratinib-induced diarrhea without concomitant administration of loperamide in female beagle dogs. A pilot study using 3 dogs determined a maximum daily tolerated dose of neratinib was between 40 and 80 mg; this dose would induce a consistent incidence/severity of diarrhea without risking severe dehydration. In the definitive study, 24 female beagle dogs (8/group) received neratinib once daily and placebo capsules (CTR) four times/day, or neratinib once daily and crofelemer 125 mg delayed-release tablets given two times (BID), or neratinib once daily and crofelemer 125 mg delayed-release tablets given four times per day (QID). Fecal scores were collected twice daily using an established canine stool scoring scale called the Purina Fecal Scoring (PFS) System. After 28 days, using analysis of covariance (ANCOVA), dogs in the CTR group had a significantly higher average number of weekly loose/watery stools (PFS of 6 or 7) when compared to either crofelemer BID (8.71±2.2 vs. 5.96±2.2, p = 0.028) or crofelemer QID (8.70±2.2 vs. 5.74±2.2, p = 0.022) treatment groups. The average number of weekly loose/watery stools were not different between the crofelemer BID and QID treatment groups (p = 0.84). This study showed that crofelemer prophylaxis reduced the incidence/severity of neratinib-associated diarrhea in female beagle dogs without the need for any loperamide administration.
Asunto(s)
Diarrea , Loperamida , Proantocianidinas , Quinolinas , Humanos , Femenino , Animales , Perros , Incidencia , Proyectos Piloto , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Diarrea/veterinariaRESUMEN
BACKGROUND: Malnutrition and liver impairment after duodenal switch (DS) are possible and undesired complications, often conservatively treated. However, in specific cases, surgical revision may be necessary. This study aims to describe outcomes achieved by two bariatric surgery centers and address effectiveness and safety of revisional surgical procedures to resolve these complications. METHODS: A retrospective chart review was performed in two bariatric surgery centers from 2008 to 2022. Patients who required revisional surgery to treat malnutrition and/or liver impairment refractory to nutritional and total parenteral nutrition intervention (TPN) after duodenal switch were included. No comparisons were performed due to the descriptive nature of this study. RESULTS: Thirteen patients underwent revisional surgery, the mean age was 44.7, the 53.8% were females, and the mean preoperative BMI was 54.7 kg/m2; the mean time between DS and revisional procedure was 26.5 months, and 69.1% of patients were placed on TPN. One patient developed hepatic encephalopathy; one patient presented with ascites, pleural effusion, and renal insufficiency, undergoing reoperation after revisional procedure due to a perforated ileal loop. Mortality rate was 0%; all patients regained weight after the revisional procedure, and the mean total protein and albumin blood levels 12 months after surgery were 6.3 and 3.6 g/dl, respectively. CONCLUSIONS: While refractory malnutrition and/or liver failure are rare among patients post-DS, if underdiagnosed and untreated, this can lead to irreversible outcomes and death. All revisional procedures included in this study resulted in improvement of the nutritional status and reversal of liver impairment, with low complication rates.
Asunto(s)
Cirugía Bariátrica , Desviación Biliopancreática , Derivación Gástrica , Hepatopatías , Desnutrición , Obesidad Mórbida , Femenino , Humanos , Adulto , Masculino , Obesidad Mórbida/cirugía , Desviación Biliopancreática/efectos adversos , Desviación Biliopancreática/métodos , Estudios Retrospectivos , Desnutrición/etiología , Desnutrición/cirugía , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/métodos , Gastrectomía/métodos , Hepatopatías/cirugía , Derivación Gástrica/métodos , Duodeno/cirugíaRESUMEN
BACKGROUND: Whether the benefits of the robotic platform in bariatric surgery translate into superior surgical outcomes remains unclear. The aim of this retrospective study was to establish the 'best possible' outcomes for robotic bariatric surgery and compare them with the established laparoscopic benchmarks. METHODS: Benchmark cut-offs were established for consecutive primary robotic bariatric surgery patients of 17 centres across four continents (13 expert centres and 4 learning phase centres) using the 75th percentile of the median outcome values until 90 days after surgery. The benchmark patients had no previous laparotomy, diabetes, sleep apnoea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI greater than 50â kg/m2, or age greater than 65 years. RESULTS: A total of 9097 patients were included, who were mainly female (75.5%) and who had a mean(s.d.) age of 44.7(11.5) years and a mean(s.d.) baseline BMI of 44.6(7.7) kg/m2. In expert centres, 13.74% of the 3020 patients who underwent primary robotic Roux-en-Y gastric bypass and 5.9% of the 4078 patients who underwent primary robotic sleeve gastrectomy presented with greater than or equal to one complication within 90 postoperative days. No patient died and 1.1% of patients had adverse events related to the robotic platform. When compared with laparoscopic benchmarks, robotic Roux-en-Y gastric bypass had lower benchmark cut-offs for hospital stay, postoperative bleeding, and marginal ulceration, but the duration of the operation was 42â min longer. For most surgical outcomes, robotic sleeve gastrectomy outperformed laparoscopic sleeve gastrectomy with a comparable duration of the operation. In robotic learning phase centres, outcomes were within the established benchmarks only for low-risk robotic Roux-en-Y gastric bypass. CONCLUSION: The newly established benchmarks suggest that robotic bariatric surgery may enhance surgical safety compared with laparoscopic bariatric surgery; however, the duration of the operation for robotic Roux-en-Y gastric bypass is longer.
Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Laparoscopía , Obesidad Mórbida , Procedimientos Quirúrgicos Robotizados , Humanos , Femenino , Anciano , Adulto , Masculino , Derivación Gástrica/efectos adversos , Obesidad Mórbida/cirugía , Benchmarking , Estudios Retrospectivos , Cirugía Bariátrica/efectos adversos , Laparoscopía/efectos adversos , Gastrectomía/efectos adversos , Resultado del TratamientoRESUMEN
The changing landscape of academia can be difficult to navigate for anyone at any point throughout their career. One thing is certainly clear: effective mentorship is key to ensuring success, fueling scientific curiosity, and creating a sense of community. This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees; it is written by Ph.D. students, postdoctoral researchers, early-stage assistant professors, and life-long educators. The objective of this article is to inform, empower, and inspire the next generation of physiologists.NEW & NOTEWORTHY This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees that is written by Ph.D. students, postdoctoral researchers, early-stage assistant professors, and life-long educators. The objective of this article is to inform, empower, and inspire the next generation of physiologists.
Asunto(s)
Mentores , Estudiantes , Humanos , Escritura , Selección de ProfesiónRESUMEN
Patients undergoing metabolic and bariatric surgery (MBS) with body mass index (BMI) ≥ 70 kg/m2 are considered a high-risk group. There is limited literature to guide surgeons on the perioperative safety as well as the different procedural outcomes of MBS in this cohort. Our aim is to compare the safety profiles, early- and medium-term outcomes of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and duodenal switch (DS) in patients with BMI ≥ 70 kg/m2. A total of 156 patients with BMI ≥ 70kg/m2 underwent MBS (SG = 40, RYGB = 40, and DS = 76). Mean baseline BMI was 75.5 kg/m2. Total weight loss (%TWL) at 24 months was highest in the DS group compared to RYGB (40.6% versus 33.8%, P value = .03) and SG (40.6% versus 28.5%, P value = .006). There was no significant difference in %TWL between RYGB and SG (33.8% versus 28.5%, P value = .20). The 30-day complication rates were similar [SG (7.5%), RYGB (10%), and DS (9.2%) (P value = 1.0)]. There was one reported leak (DS). The 30-day mortality was zero. MBS is safe and effective in patients with BMI ≥ 70 kg/m2. All procedures had comparable safety profiles and complication rates. While DS achieved the highest %TWL at 24 months, similar comorbidity resolution rates among the procedures attenuate its clinical significance.
Asunto(s)
Derivación Gástrica , Obesidad Mórbida , Humanos , Derivación Gástrica/métodos , Obesidad Mórbida/cirugía , Índice de Masa Corporal , Estudios de Seguimiento , Estudios Retrospectivos , Gastrectomía/métodos , Resultado del Tratamiento , Estudios Multicéntricos como AsuntoRESUMEN
Accurate and efficient affinity measurement techniques are essential for the biophysical characterization of therapeutic monoclonal antibodies, one of the fastest growing drug classes. Surface plasmon resonance (SPR) is widely used for determining antibody affinity, but does not perform well with extremely high affinity (low picomolar to femtomolar range) molecules. In this study, we compare the SPR-based Carterra LSA and the kinetic exclusion assay (KinExA) for measuring the affinities of 48 antibodies generated against the SARS-CoV-2 receptor-binding domain. These data reveal that high-affinity antibodies can be generated straight from selections using high-quality in vitro library platforms with 54% correspondence between affinities measured using LSA and KinExA. Generally, where there was a 2-fold or greater difference between LSA and KinExA, KinExA reported that affinities were tighter. We highlight the differences between LSA and KinExA, identifying the benefits and pitfalls of each in terms of dynamic range and throughput. Furthermore, we demonstrate for the first time that single-point screening with KinExA can significantly improve throughput while maintaining a strong correlation with full binding curve equilibrium measurements, enabling the accurate rank-ordering of clones with exceptionally tight binding properties.
Asunto(s)
Anticuerpos Monoclonales , Resonancia por Plasmón de Superficie , Resonancia por Plasmón de Superficie/métodos , Anticuerpos Monoclonales/química , Afinidad de AnticuerposRESUMEN
Botulism is a rare cause of flaccid paralysis resulting from the neurotoxin produced by the bacterium Clostridium botulinum. It is clinically characterized by symmetric proximal-distal paralysis, diplopia, dysarthria, dysphonia, and dysphagia. Definitive diagnosis requires laboratory confirmation through the detection of the toxin in blood, vomit, or stool samples. Treatment with antitoxin should be promptly initiated upon clinical suspicion and in the presence of epidemiological support due to evidence of reduced mortality. Physical and rehabilitation medicine plays a fundamental role in the recovery of deficits and prevention of complications. In this report, the authors describe a 19-year-old patient with botulism with dysphagia, dysphonia, and facial paresis in the rehabilitation ward.
RESUMEN
Caudal epidural block is a procedure that involves the injection of anesthetic agents through the sacral hiatus, commonly used for regional anesthesia. It is also valuable for chronic pain management in lumbosacral conditions, trauma, and palliative care. Ultrasound-guided caudal epidural blocks can be an alternative to fluoroscopy-guided techniques and have demonstrated a notably high success rate. However, despite both techniques being generally regarded as safe, they can lead to severe complications, such as abscesses, epidural hematomas, and subdural punctures. Furthermore, documented instances of lumbosacral region anomalies, stemming from either anatomical variations or underlying pathology, have been associated with an elevated risk of some of these complications. The authors report a rare case of paraplegia following an ultrasound-guided caudal block in a patient with refractory chronic lumbosciatica. This case underscores the need for vigilance in risk assessment and detailed procedural planning. It also highlights the importance of transparent communication, particularly during informed consent, to convey risks and benefits to the patient and their family.