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.

A multi-dimensional analysis of genotype-phenotype discordance in malignant hyperthermia susceptibility.

BACKGROUND: Malignant hyperthermia (MH) susceptibility is an inherited condition, diagnosed either by the presence of a pathogenic genetic variant or by in vitro caffeine-halothane contracture testing. Through a multi-dimensional approach, we describe the implications of discordance between genetic and in vitro test results in a patient with a family history of possible MH. METHODS: The patient, whose brother had a possible MH reaction, underwent the caffeine-halothane contracture test (CHCT) according to the North American MH Group protocol. Screening of the complete RYR1 and CACNA1S transcripts was done using Sanger sequencing. Additional functional analyses included skinned myofibre calcium-induced calcium release sensitivity, calcium signalling assays in cultured myotubes, and in silico evaluation of the effect of any genetic variants on their chemical environment. RESULTS: The patient's CHCT result was negative but she carried an RYR1 variant c.1209C>G, p.Ile403Met, that is listed as pathogenic by the European Malignant Hyperthermia Group. Functional tests indicated a gain-of-function effect with a weak impact, and the variant was predicted to affect the folding stability of the 3D structure of the RyR1 protein. Based on American College of Medical Genetics and Genomics/Association of Molecular Pathology guidelines, this variant would be characterised as a variant of uncertain significance. CONCLUSIONS: Available data do not confirm or exclude an increased risk of MH for this patient. Further research is needed to correlate RyR1 functional assays, including the current gold standard testing for MH susceptibility, with clinical phenotypes. The pathogenicity of genetic variants associated with MH susceptibility should be re-evaluated.

Calsequestrin depolymerizes when calcium is depleted in the sarcoplasmic reticulum of working muscle.

Calsequestrin, the only known protein with cyclical storage and supply of calcium as main role, is proposed to have other functions, which remain unproven. Voluntary movement and the heart beat require this calcium flow to be massive and fast. How does calsequestrin do it? To bind large amounts of calcium in vitro, calsequestrin must polymerize and then depolymerize to release it. Does this rule apply inside the sarcoplasmic reticulum (SR) of a working cell? We answered using fluorescently tagged calsequestrin expressed in muscles of mice. By FRAP and imaging we monitored mobility of calsequestrin as [Ca2+] in the SR--measured with a calsequestrin-fused biosensor--was lowered. We found that calsequestrin is polymerized within the SR at rest and that it depolymerized as [Ca2+] went down: fully when calcium depletion was maximal (a condition achieved with an SR calcium channel opening drug) and partially when depletion was limited (a condition imposed by fatiguing stimulation, long-lasting depolarization, or low drug concentrations). With fluorescence and electron microscopic imaging we demonstrated massive movements of calsequestrin accompanied by drastic morphological SR changes in fully depleted cells. When cells were partially depleted no remodeling was found. The present results support the proposed role of calsequestrin in termination of calcium release by conformationally inducing closure of SR channels. A channel closing switch operated by calsequestrin depolymerization will limit depletion, thereby preventing full disassembly of the polymeric calsequestrin network and catastrophic structural changes in the SR.

Artificial intelligence approaches to the volumetric quantification of glycogen granules in EM images of human tissue.

Skeletal muscle, the major processor of dietary glucose, stores it in myriad glycogen granules. Their numbers vary with cellular location and physiological and pathophysiological states. AI models were developed to derive granular glycogen content from electron-microscopic images of human muscle. Two UNet-type semantic segmentation models were built: "Locations" classified pixels as belonging to different regions in the cell; "Granules" identified pixels within granules. From their joint output, a pixel fraction pf was calculated for images from patients positive (MHS) or negative (MHN) to a test for malignant hyperthermia susceptibility. pf was used to derive vf, the volume fraction occupied by granules. The relationship vf (pf) was derived from a simulation of volumes ("baskets") containing virtual granules at realistic concentrations. The simulated granules had diameters matching the real ones, which were measured by adapting a utility devised for calcium sparks. Applying this relationship to the pf measured in images, vf was calculated for every region and patient, and from them a glycogen concentration. The intermyofibrillar spaces and the sarcomeric I band had the highest granular content. The measured glycogen concentration was low enough to allow for a substantial presence of non-granular glycogen. The MHS samples had an approximately threefold lower concentration (significant in a hierarchical test), consistent with earlier evidence of diminished glucose processing in MHS. The AI models and the approach to infer three-dimensional magnitudes from two-dimensional images should be adaptable to other tasks on a variety of images from patients and animal models and different disease conditions.

Dynamic measurement of the calcium buffering properties of the sarcoplasmic reticulum in mouse skeletal muscle.

The buffering power, B, of the sarcoplasmic reticulum (SR), ratio of the changes in total and free [Ca(2+)], was determined in fast-twitch mouse muscle cells subjected to depleting membrane depolarization. Changes in total SR [Ca(2+)] were measured integrating Ca(2+) release flux, determined with a cytosolic [Ca(2+)] monitor. Free [Ca(2+)](SR) was measured using the cameleon D4cpv-Casq1. In 34 wild-type (WT) cells average B during the depolarization (ON phase) was 157 (SEM 26), implying that of 157 ions released, 156 were bound inside the SR. B was significantly greater when BAPTA, which increases release flux, was present in the cytosol. B was greater early in the pulse - when flux was greatest - than at its end, and greater in the ON than in the OFF. In 29 Casq1-null cells, B was 40 (3.6). The difference suggests that 75% of the releasable calcium is normally bound to calsequestrin. In the nulls the difference in B between ON and OFF was less than in the WT but still significant. This difference and the associated decay in B during the ON were not artifacts of a slow SR monitor, as they were also found in the WT when [Ca(2+)](SR) was tracked with the fast dye fluo-5N. The calcium buffering power, binding capacity and non-linear binding properties of the SR measured here could be accounted for by calsequestrin at the concentration present in mammalian muscle, provided that its properties were substantially different from those found in solution. Its affinity should be higher, or K(D) lower than the conventionally accepted 1 mm; its cooperativity (n in a Hill fit) should be higher and the stoichiometry of binding should be at the higher end of the values derived in solution. The reduction in B during release might reflect changes in calsequestrin conformation upon calcium loss.

Altered Ca2+ concentration, permeability and buffering in the myofibre Ca2+ store of a mouse model of malignant hyperthermia.

Malignant hyperthermia (MH) is linked to mutations in the type 1 ryanodine receptor, RyR1, the Ca2+ channel of the sarcoplasmic reticulum (SR) of skeletal muscle. The Y522S MH mutation was studied for its complex presentation, which includes structurally and functionally altered cell 'cores'. Imaging cytosolic and intra-SR [Ca2+] in muscle cells of heterozygous YS mice we determined Ca2+ release flux activated by clamp depolarization, permeability (P) of the SR membrane (ratio of flux and [Ca2+] gradient) and SR Ca2+ buffering power (B). In YS cells resting [Ca2+]SR was 45% of the value in normal littermates (WT). P was more than doubled, so that initial flux was normal. Measuring [Ca2+]SR(t) revealed dynamic changes in B(t). The alterations were similar to those caused by cytosolic BAPTA, which promotes release by hampering Ca2+-dependent inactivation (CDI). The [Ca2+] transients showed abnormal 'breaks', decaying phases after an initial rise, traced to a collapse in flux and P. Similar breaks occurred in WT myofibres with calsequestrin reduced by siRNA; calsequestrin content, however, was normal in YS muscle. Thus, the Y522S mutation causes greater openness of the RyR1, lowers resting [Ca2+]SR and alters SR Ca2+ buffering in a way that copies the functional instability observed upon reduction of calsequestrin content. The similarities with the effects of BAPTA suggest that the mutation, occurring near the cytosolic vestibule of the channel, reduces CDI as one of its primary effects. The unstable SR buffering, mimicked by silencing of calsequestrin, may help precipitate the loss of Ca2+ control that defines a fulminant MH event.

Muscle calcium stress cleaves junctophilin1, unleashing a gene regulatory program predicted to correct glucose dysregulation.

Calcium ion movements between cellular stores and the cytosol govern muscle contraction, the most energy-consuming function in mammals, which confers skeletal myofibers a pivotal role in glycemia regulation. Chronic myoplasmic calcium elevation ("calcium stress"), found in malignant hyperthermia-susceptible (MHS) patients and multiple myopathies, has been suggested to underlie the progression from hyperglycemia to insulin resistance. What drives such progression remains elusive. We find that muscle cells derived from MHS patients have increased content of an activated fragment of GSK3ß - a specialized kinase that inhibits glycogen synthase, impairing glucose utilization and delineating a path to hyperglycemia. We also find decreased content of junctophilin1, an essential structural protein that colocalizes in the couplon with the voltage-sensing CaV1.1, the calcium channel RyR1 and calpain1, accompanied by an increase in a 44 kDa junctophilin1 fragment (JPh44) that moves into nuclei. We trace these changes to activated proteolysis by calpain1, secondary to increased myoplasmic calcium. We demonstrate that a JPh44-like construct induces transcriptional changes predictive of increased glucose utilization in myoblasts, including less transcription and translation of GSK3ß and decreased transcription of proteins that reduce utilization of glucose. These effects reveal a stress-adaptive response, mediated by the novel regulator of transcription JPh44.

Primary Orbital Myxoid Liposarcoma.

Although liposarcoma is the most prevalent soft tissue sarcoma in adults, head and neck liposarcomas are rare and account for less than 5% of all liposarcomas. The primary orbital location is even more exceptional, with fewer than 100 cases documented in the medical literature. Given the scarcity of cases of orbital liposarcoma and the limited familiarity of physicians and pathologists with this pathology, there is an increased risk of non-diagnosis or misdiagnosis, which may lead to inappropriate patient management. To address these challenges, we present a case of primary orbital myxoid liposarcoma and subsequently discuss the primary findings of this case based on the evidence documented in the medical literature. This comprehensive text is designed to serve as a valuable resource for healthcare professionals and pathologists, with the goal of promoting both clinical suspicion and accurate diagnosis and treatment of this rare condition in future cases.

Roux-en-Y partial volvulus in biliary-digestive reconstruction in children.

Various complications occur after a biliary-digestive reconstruction. Volvulus of a segment of the biliodigestive loop has not been described. Two patients who underwent biliodigestive bypass, years later, began with sudden and intense abdominal pain, associated with a volvulus with necrosis of a segment of this biliodigestive loop. This complication occurred many years after the initial correction, and manifested with sudden abdominal pain without impaired liver function, as occurred in these patients.

Diversas complicaciones pueden ocurrir después de una reconstrucción biliodigestiva. El vólvulo de un segmento del asa biliodigestiva no ha sido descrito. Dos pacientes operados de derivación biliodigestiva, años después iniciaron con dolor abdominal súbito e intenso, asociado a un vólvulo con necrosis de un segmento de la asa interpuesta. Se ha descrito el vólvulo de toda el asa interpuesta, pero no el de solo una pequeña porción de esta. La complicación ocurrió muchos años después de la corrección inicial y se manifiesto con dolor abdominal súbito sin deterioro de la función hepática, como sucedió en estos pacientes.

Synthetic localized calcium transients directly probe signalling mechanisms in skeletal muscle.

The contribution of Ca2+-induced Ca2+ release (CICR) to trigger muscle contraction is controversial. It was studied on isolated muscle fibres using synthetic localized increases in Ca2+ concentration, SLICs, generated by two-photon photorelease from nitrodibenzofuran (NDBF)-EGTA just outside the permeabilized plasma membrane. SLICs provided a way to increase cytosolic [Ca2+] rapidly and reversibly, up to 8 µM, levels similar to those reached during physiological activity. They improve over previous paradigms in rate of rise, locality and reproducibility. Use of NDBF-EGTA allowed for the separate modification of resting [Ca2+], trigger [Ca2+] and resting [Mg2+]. In frog muscle, SLICs elicited propagated responses that had the characteristics of CICR. The threshold [Ca2+] for triggering a response was 0.5 µM or less. As this value is much lower than concentrations prevailing near channels during normal activity, the result supports participation of CICR in the physiological control of contraction in amphibian muscle. As SLICs were applied outside cells, the primary stimulus was Ca2+, rather than the radiation or subproducts of photorelease. Therefore the responses qualify as 'classic' CICR. By contrast, mouse muscle fibres did not respond unless channel-opening drugs were present at substantial concentrations, an observation contrary to the physiological involvement of CICR in mammalian excitation­contraction coupling. In mouse muscle, the propagating wave had a substantially lower release flux, which together with a much higher threshold justified the absence of response when drugs were not present. The differences in flux and threshold may be ascribed to the absence of ryanodine receptor 3 (RyR3) isoforms in adult mammalian muscle.

A novel method for determining murine skeletal muscle fiber type using autofluorescence lifetimes.

This work describes a simple way to identify fiber types in living muscles by fluorescence lifetime imaging microscopy (FLIM). We quantified the mean values of lifetimes τ1 and τ2 derived from a two-exponential fit in freshly dissected mouse flexor digitorum brevis (FDB) and soleus muscles. While τ1 values changed following a bimodal behavior between muscles, the distribution of τ2 is shifted to higher values in FDB. To understand the origin of this difference, we obtained maps of autofluorescence lifetimes of flavin mononucleotide and dinucleotide (FMN/FAD) in cryosections, where excitation was set at 440 nm and emission at a bandwidth of between 500 and 570 nm, and paired them with immunofluorescence images of myosin heavy chain isoforms, which allowed identification of fiber types. In soleus, τ2 was 3.16 ns for type I (SD 0.11, 97 fibers), 3.45 ns for IIA (0.10, 69), and 3.46 ns for IIX (0.12, 65). In FDB muscle, τ2 was 3.17 ns for type I (0.08, 22), 3.46 ns for IIA (0.16, 48), and 3.66 ns for IIX (0.15, 43). From τ2 distributions, it follows that an FDB fiber with τ2 > 3.3 ns is expected to be of type II, and of type I otherwise. This simple classification method has first and second kind errors estimated at 0.02 and 0.10, which can be lowered by reducing the threshold for identification of type I and increasing it for type II. Lifetime maps of autofluorescence, therefore, constitute a tool to identify fiber types that, for being practical, fast, and noninvasive, can be applied in living tissue without compromising other experimental interventions.

Quantification of the calcium signaling deficit in muscles devoid of triadin.

Triadin, a protein of the sarcoplasmic reticulum (SR) of striated muscles, anchors the calcium-storing protein calsequestrin to calcium release RyR channels at the junction with t-tubules, and modulates these channels by conformational effects. Triadin ablation induces structural SR changes and alters the expression of other proteins. Here we quantify alterations of calcium signaling in single skeletal myofibers of constitutive triadin-null mice. We find higher resting cytosolic and lower SR-luminal [Ca2+], 40% lower calsequestrin expression, and more CaV1.1, RyR1 and SERCA1. Despite the increased CaV1.1, the mobile intramembrane charge was reduced by ~20% in Triadin-null fibers. The initial peak of calcium release flux by pulse depolarization was minimally altered in the null fibers (revealing an increase in peak calcium permeability). The "hump" phase that followed, attributable to calcium detaching from calsequestrin, was 25% lower, a smaller change than expected from the reduced calsequestrin content and calcium saturation. The exponential decay rate of calcium transients was 25% higher, consistent with the higher SERCA1 content. Recovery of calcium flux after a depleting depolarization was faster in triadin-null myofibers, consistent with the increased uptake rate and lower SR calsequestrin content. In sum, the triadin knockout determines an increased RyR1 channel openness, which depletes the SR, a substantial loss of calsequestrin and gains in other couplon proteins. Powerful functional compensations ensue: activation of SOCE that increases [Ca2+]cyto; increased SERCA1 activity, which limits the decrease in [Ca2+]SR and a restoration of SR calcium storage of unknown substrate. Together, they effectively limit the functional loss in skeletal muscles.

Celiac disease in children, adolescents, and young adults with autoimmune thyroid disease.

OBJECTIVE: To determine the prevalence of antibodies associated with celiac disease and biopsy-proven celiac disease in children with autoimmune thyroid disease. STUDY DESIGN: A total of 302 patients with positive anti-thyroid antibodies were prospectively studied. Total immunoglobulin A (IgA) and tissue transglutaminase-IgA (tTG-IgA) levels were obtained. Those with a positive tTG-IgA titer were offered biopsy for definitive diagnosis of celiac disease. RESULTS: A total of 4.6% of subjects with autoimmune thyroid disease had positive tTG-IgA titers. The prevalence of biopsy-confirmed celiac disease was 2.3%. Our population was enriched with patients with type 1 diabetes mellitus (4.3%) and Down syndrome (3.4%). Excluding individuals with these co-morbidities, the prevalence of celiac disease in autoimmune thyroid disease is 1.3%, similar to that of the general population. The positive predictive value of biopsy-proven celiac disease in patients with autoimmune thyroid disease and positive tTG-IgA titer was 54%. CONCLUSION: The increase in prevalence of celiac disease in autoimmune thyroid disease in our study was largely caused by enrichment with co-morbidities. Without comorbidities or symptoms, screening for celiac disease may not be justified in this population. The specificity of tTG-IgA titer for the diagnosis of celiac disease was decreased in patients with autoimmune thyroid disease compared with the general population.

Treatment of chronic pancreatitis by laparoscopic DuVal procedure: report of a pediatric case.

ANTECEDENTES: La pancreatitis es una enfermedad rara. La obstrucción es común y se puede corregir con endoscopia; si fracasa, necesitará cirugía. CASO CLÍNICO: Reportamos un paciente con pancreatitis secundaria a páncreas divisum. Se realizó derivación tipo DuVal laparoscópica. Varón de 12 años, con múltiples cuadros de pancreatitis y fallidos intentos de esfinteroplastias. La colangiorresonancia mostró páncreas divisum. Se realizó una derivación tipo DuVal por laparoscopia. Seguimiento de 5 años. No ha habido recurrencia del dolor y la lipasa se normalizó a los 6 meses. El conducto pancreático no estaba dilatado. Ante la dificultad para hacer una anastomosis lateral se utilizó la técnica laparoscópica propuesta por DuVal. BACKGROUND: Pancreatitis is rare. Obstruction is common. They can be corrected with endoscopy, if they fail they need surgery. CASE REPORT: We reported a patient with pancreatitis secondary to pancreas divisum, laparoscopic DuVal shunt was performed. Male 12 years, multiple pancreatitis pictures and failed sphinteroplasty attempts. Colangio resonance showed pancreas divisum. A DuVal-type shunt was built for laparoscopy. Follow-up 5 years. There has been no recurrence of pain and lipase was normalized at 6 months. The pancreatic duct was not dilated, in the face of difficulty making a lateral anastomosis was used the technique proposed by DuVal by laparoscopic approach.

Intraoperative Endoscopy as an Adjuvant to Minimally Invasive Surgery in Pediatrics.

Background: Minimally invasive surgery has a different visual and tactile perception compared with conventional surgery, which could lead to complications, especially in complex procedures. In these cases, flexible endoscopy can facilitate and prevent complications in minimally invasive procedures in children. The study aimed to clarify the utility of intraoperative endoscopy as an adjuvant to minimally invasive surgery in children. Materials and Methods: This retrospective study reviewed the medical records of pediatric patients who had undergone endoscopy during a minimally invasive surgery to treat an upper digestive pathology between January 2000 and December 2020. Results: The study included 83 patients who underwent a laparoscopic procedure with simultaneous endoscopy. The diagnosis was peptic stenosis in 9 patients, achalasia in 23, congenital embryonic tracheobronchial remnants in 4, re-fundoplication in 42, esophageal duplication in 2, superior mesenteric artery syndrome in 2, and giant gastric hemangioma in 1 patient. With adjuvant endoscopy, 7 digestive perforations were noted, 11 cases of short esophagus were diagnosed, and the permeability of the anastomosis was confirmed in 6 cases. No complications were related with the endoscopy procedures. Discussion: Minimally invasive surgery has a few special and tactile limitations that can lead to complications in certain procedures. Simultaneous digestive endoscopy in the upper gastrointestinal tract facilitates organ identification and dissection. Conclusion: Digestive endoscopy is an excellent adjunct to minimally invasive surgery in children because it facilitates and identifies complications and ensures safer minimally invasive surgeries. Future prospective studies are required to assess this conclusion.

Tratamiento laparoscópico de un quiste de colédoco gigante en un paciente pediátrico.

Introducción: Se define como quiste de colédoco gigante aquel con un diámetro ≥ 10 cm. A pesar de que el abordaje laparoscópico ha sido contraindicado, se presenta el caso de un adolescente con un quiste de colédoco gigante resuelto por laparoscopía. Caso clínico: Paciente de sexo masculino de 14 años con un quiste de colédoco gigante tratado con anastomosis hepático-duodenal laparoscópica. Conclusiones: El tamaño promedio de los quistes de colédoco tratados por laparoscopía es de 40 mm. No se recomienda la resección de quistes gigantes por mínima invasión debido a adherencias y restricción del campo visual. En este caso se realizó un tratamiento laparoscópico de manera exitosa.

Intracellular calcium leak lowers glucose storage in human muscle, promoting hyperglycemia and diabetes.

Most glucose is processed in muscle, for energy or glycogen stores. Malignant Hyperthermia Susceptibility (MHS) exemplifies muscle conditions that increase [Ca2+]cytosol. 42% of MHS patients have hyperglycemia. We show that phosphorylated glycogen phosphorylase (GPa), glycogen synthase (GSa) - respectively activated and inactivated by phosphorylation - and their Ca2+-dependent kinase (PhK), are elevated in microsomal extracts from MHS patients' muscle. Glycogen and glucose transporter GLUT4 are decreased. [Ca2+]cytosol, increased to MHS levels, promoted GP phosphorylation. Imaging at ~100 nm resolution located GPa at sarcoplasmic reticulum (SR) junctional cisternae, and apo-GP at Z disk. MHS muscle therefore has a wide-ranging alteration in glucose metabolism: high [Ca2+]cytosol activates PhK, which inhibits GS, activates GP and moves it toward the SR, favoring glycogenolysis. The alterations probably cause these patients' hyperglycemia. For basic studies, MHS emerges as a variable stressor, which forces glucose pathways from the normal to the diseased range, thereby exposing novel metabolic links.

Animals and humans move by contracting the skeletal muscles attached to their bones. These muscles take up a type of sugar called glucose from food and use it to fuel contractions or store it for later in the form of glycogen. If muscles fail to use glucose it can lead to excessive sugar levels in the blood and a condition called diabetes. Within muscle cells are stores of calcium that signal the muscle to contract. Changes in calcium levels enhance the uptake of glucose that fuel these contractions. However, variations in calcium have also been linked to diabetes, and it remained unclear when and how these 'signals' become harmful. People with a condition called malignant hyperthermia susceptibility (MHS for short) have genetic mutations that allow calcium to leak out from these stores. This condition may result in excessive contractions causing the muscle to over-heat, become rigid and break down, which can lead to death if left untreated. A clinical study in 2019 found that out of hundreds of patients who had MHS, nearly half had high blood sugar and were likely to develop diabetes. Now, Tammineni et al. ­ including some of the researchers involved in the 2019 study ­ have set out to find why calcium leaks lead to elevated blood sugar levels. The experiments showed that enzymes that help convert glycogen to glucose are more active in patients with MHS, and found in different locations inside muscle cells. Whereas the enzymes that change glucose into glycogen are less active. This slows down the conversion of glucose into glycogen for storage and speeds up the breakdown of glycogen into glucose. Patients with MHS also had fewer molecules that transport glucose into muscle cells and stored less glycogen. These changes imply that less glucose is being removed from the blood. Next, Tammineni et al. used a microscopy technique that is able to distinguish finely separated objects with a precision not reached before in living muscle. This revealed that when the activity of the enzyme that breaks down glycogen increased, it moved next to the calcium store. This effect was also observed in the muscle cells of MHS patients that leaked calcium from their stores. Taken together, these observations may explain why patients with MHS have high levels of sugar in their blood. These findings suggest that MHS may start decades before developing diabetes and blood sugar levels in these patients should be regularly monitored. Future studies should investigate whether drugs that block calcium from leaking may help prevent high blood sugar in patients with MHS or other conditions that cause a similar calcium leak.

Laparoscopic Collis-Nissen approach for shortened esophagus treatment in children.

BACKGROUND: Short esophagus is a disability to obtain a proper portion of abdominal esophagus, thus a lengthening technique is required. Collis approach is the best option. OBJECTIVE: To demonstrate effectiveness of laparoscopic Collis-Nissen approach in children. METHOD: Retrospective and descriptive case series performed in children with reflux and short esophagus, Collis esophagoplasty was carried out with stapler, together with fundoplication. Age, symptomatology, surgical background, oral nutrition beginning, hospital stay, complications and reflux control were recorded. RESULTS: Eight children, 4-15 years old were treated from 2005 to 2017. Three of them with slipped fundoplication background and two with esophageal atresia. The rest of the children had no background, two of them with stenosis. Symptoms; cough 8/8, abdominal pain 5/8, dysphagia 3/8. Without complications. Oral nutrition beginning at the 5th day. Up to 10 years follow-up, with complete remission of the symptomatology in 6 years. DISCUSSION: Since a true short esophagus diagnosis depends on transurgical findings, pediatric surgeons should notice this entity when practicing any antireflux procedure. Laparoscopic Collis-Nissen approach is safe and efficient in these patients.

ANTECEDENTES: El esófago corto es la imposibilidad de obtener una porción adecuada de esófago abdominal, por lo que se requiere alguna técnica de alargamiento. La mejor opción es el procedimiento de Collis. OBJETIVO: Demostrar la eficacia del procedimiento de Collis-Nissen por laparoscopía en niños. MÉTODO: Estudio retrospectivo, descriptivo, serie de casos, niños con reflujo y esófago corto, esofagoplastía de Collis con engrapadora y funduplicatura. Se analizaron edad, sintomatología, antecedentes quirúrgicos, tiempo quirúrgico, inicio de vía oral, tiempo de hospitalización, complicaciones y control del reflujo. RESULTADOS: De 2005 a 2017 se trataron ocho niños de 4 a 15 años. De ellos, tres con antecedente de funduplicatura deslizada y dos con antecedente de atresia esofágica. El resto sin antecedentes, dos con estenosis. Síntomas; tos 8/8, dolor abdominal 5/8, disfagia 3/8. Sin complicaciones. Inició de vía oral al quinto día. Seguimiento de hasta 10 años, con remisión total de la sintomatología en seis casos. DISCUSIÓN: Debido a que el diagnóstico de esófago corto verdadero depende de los hallazgos transoperatorios, los cirujanos pediatras deben reconocer esta condición al momento de practicar cualquier procedimiento antirreflujo. El procedimiento de Collis-Nissen laparoscópico es una opción segura y eficaz en estos pacientes.

Laparoscopic Approach of the Obstruction of the Lower Third of the Esophagus in Children.

Objective: To review the diagnostic methodology in pediatric patients with obstruction of the lower third of the esophagus as well as minimally invasive therapeutic options. Materials and Methods: Retrospective study carried out reviewing records of children with esophageal obstruction diagnostic, from 2000 to 2018. They were divided into Group I stenosis secondary to reflux; Group II achalasia; and Group III embryonic remnants. Results: Thirty-three patients. Group I: 7; esophageal barium swallow irregular stenosis of the distal third and endoscopy irregular stenosis in 7. Treated with laparoscopic fundoplication 2, Collis Nissen 5. Group II: 22 patients, age X = 11.55 years. All with dysphagia and symmetrical stenosis of esophagogastric junction. Fifteen underwent manometry and all underwent intraoperative endoscopy. All had laparoscopic myotomy, with 2 perforations and no conversions, 2 patients had subsequent dysphagia to solids, and they did not need esophageal dilatation. Group III: 4 patients, stenosis was above esophagogastric junction. On endoscopy, inflammation was present in all 3 with irregular esophagogastric junction and difficulty passing endoscope. Three patients underwent laparoscopic resection and anastomosis. One patient leaked and developed a fistula. One patient has not been operated upon as yet. Conclusions: In those patients, the best surgical option depends upon the diagnosis. Esophageal barium studies and endoscopy allow discerning among them.

Femoral hernia in children: diagnostic and therapeutic challenge. Case report.

INTRODUCCIÓN: Las hernias femorales son raras en la infancia. El defecto está abajo del ligamento inguinal. La frecuencia de un diagnóstico erróneo es de hasta el 75%. Pueden ser resueltas mediante cirugía abierta o laparoscópica. OBJETIVO: Comunicar el caso de un niño con hernia femoral resuelto mediante laparoscopía. CASO CLÍNICO: Varón de 5 años, con antecedente de criptorquidia bilateral resuelta a los 2 años de edad. Padecimiento actual con 1 mes de evolución, con aumento de volumen en el tercio externo de la ingle. El ultrasonido reportó un defecto aponeurótico junto a los vasos femorales derechos. Abordaje laparoscópico, con hallazgos de defecto por abajo del ligamento inguinal. Sin recidiva a los 12 meses de seguimiento. DISCUSIÓN: Las hernias femorales son raras en los niños y su diagnóstico es difícil. La exploración laparoscópica permitió identificarla al encontrar un defecto por abajo del ligamento inguinal y junto a los vasos femorales independiente del anillo inguinal profundo y de la fascia transversal. INTRODUCTION: Femoral hernias are rare in children. The defect is below the inguinal ligament. The frequency of a misdiagnosis is up to 75%. They can be resolved by open or laparoscopic surgery. OBJECTIVE: To report the case of a child with femoral hernia, resolved by laparoscopy. CASE REPORT: Male, 5 years old, with a history of bilateral cryptorchidism resolved at 2 years of age. Current condition with a month of evolution with an increase in volume in the outer third of the groin. Ultrasound reported aponeurotic defect along with the right femoral vessels. Laparoscopic approach, with defect findings below the inguinal ligament. No recurrence at 12 months follow-up. DISCUSSION: Femoral hernias are rare in children, their diagnosis is difficult. Laparoscopic examination allowed its identification, finding a defect below the inguinal ligament and adjacent to the femoral vessels independent of the deep inguinal ring and the transversalis fascia.