Yasmine Aramon, Andrea Pieragostini, Pierre Jean Francin
et al.
Abstract The outcome of multiple myeloma (MM) has tremendously improved over the past decade, due to the development of efficient chemotherapy and mostly immunotherapy. Yet, some patients still display poor responses and outcome. This could be in part related to the presence of peripheral plasma cells, at levels not compatible with a diagnosis of plasma‐cell leukaemia. Some recent publications have highlighted the prognostic influence of low levels of such cells which is around 0.1%. Automated blood cell analysers now include fluorescent staining, allowing to identify cells with higher levels or nucleic acids such as activated B‐lymphocytes/plasma cells with highly active ribosomal activity related to antibody production. Here, a prospective evaluation of peripheral high fluorescent lymphoid cell (HFLC) levels was carried out on samples from patients with newly diagnosed MM, and data computed with regard to patient evolution. HFLC above a 0.1% threshold were identified as strongly correlated with poorer response in a cohort of 127 patients. The 74 patients with low HFLC had a significantly better PFS both in univariate (p = 0.0017) and multivariate (p = 0.0007) analyses. This simple test provides a significant prognostic value for patients with MM and could eventually lead clinicians to consider more aggressive strategies for patients with peripheral HFLC above 0.1%. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission
Pimsiri Sripongpun, Apichat Kaewdech, Prowpanga Udompap
et al.
Background & Aims: The new nomenclature of steatotic liver disease (SLD) was recently launched with sub-classifications of metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-related liver disease (ALD). Herein, we aimed to evaluate the characteristics and long-term outcomes associated with these subgroups and the utility of non-invasive biomarkers. Methods: Using NHANES III (the third National Health and Nutrition Examination Survey) and linked mortality data, all adult participants with available ultrasonographic liver steatosis status were included. Those with viral hepatitis, incomplete data on alcohol consumption, cardiometabolic risk, and missing data that hindered Steatosis-associated Fibrosis Estimator (SAFE) score calculation were excluded. The characteristics of those without SLD (no steatosis on ultrasound), MASLD, MetALD, and ALD were compared. Overall survival (OS) was determined and SAFE score strata were applied to SLD subgroups. Results: A total of 9,939 participants were eligible; 64% had no SLD, while 30%, 2.3%, and 1% had MASLD, MetALD, and ALD, respectively. A higher proportion of men, as well as active smokers, was observed in the MetALD and ALD groups compared to the MASLD group. Diabetes was more prevalent in the MASLD group than in the MetALD and ALD groups. The ALD subgroup had significantly lower OS than the MASLD group (p = 0.004), but the MetALD did not (p = 0.165). SAFE score strata meaningfully differentiated OS of all SLD subgroups. Conclusions: MASLD accounted for the largest proportion of SLD. MetALD shared the characteristics of both MASLD and ALD. The ALD subgroup had a significantly lower OS than the MASLD subgroup but there was no difference between MetALD and MASLD. The SAFE score can be used to stratify long-term outcomes in all SLD subgroups. Impact and implications:: “Steatotic liver disease (SLD)” is a recently introduced term covering three subgroups: MASLD (metabolic dysfunction-associated SLD), MetALD (MASLD with increased alcohol intake), and ALD (alcohol-related liver disease). We explored the characteristics and outcomes of these subgroups among the US population. We found that MASLD was far more common than MetALD and ALD, but all subgroups shared cardiometabolic risk factors. The ALD subgroup has the worst survival, pointing to the synergistic effect of alcohol and metabolic dysfunction. In addition, the SAFE (Steatosis-associated Fibrosis Estimator) score might be a useful non-invasive test to stratify long-term risk in all three SLD subgroups.
Diseases of the digestive system. Gastroenterology
Mental illnesses have a significant impact on the lives of people not only because of their morbidity but also because of their noticeable impact on economic wellbeing. Out-of-pocket expenditure for mental healthcare services is significant in India and may even lead to impoverishment of the families. The present paper states that Health Technology Assessment (HTA) is necessary for mental healthcare primarily because of its rising cost and competing interests in government decisions and prioritization. HTA does a systematic evaluation of the consequences of using health technology. HTA will provide information to decision makers to develop and implement safer, cost-effective, and efficient policies at the individual and government levels. Appropriate guidance regarding the cost-effectiveness of mental health interventions will help to serve the purpose of providing transparent reports in the context of limited budgets.
Mast Cell Activation Syndrome (MCAS) is a severe relapsing disease requiring inpatient treatment, with clinical pattern including the features of anaphylaxis. The article presents diagnostic criteria aimed for differentiation of MCAS from similar severe conditions as well as discusses local forms of mast cell activation. The consensus group has established distinct criteria for diagnosing MCAS. The agreed criteria include episodic (recurrent) occurrence of typical systemic symptoms caused by release of mast cell mediators and involve, at least, two organs; an increase in serum tryptase level by, at least, 20% over individual baseline tryptase plus 2 ng/mL tryptase during 3-4 hours of the pathological reaction; a positive response to drugs that either target mast cells mediators, or their effects. In principle, the classification of MCAS is based on its etiology being subdivided into primary (clonal) MCAS, secondary MCAS, and idiopathic MCAS. The primary MCAS is determined by clonal expansion of mast cells and is considered systemic mastocytosis. In secondary MCAS, normal mast cells are activated by the known triggers, e.g., IgE. If neither clonal expansion nor a trigger for mast cells activation are identified, the condition is defined as idiopathic MCAS.The new COVID-19 infection has attracted particular interest in MCAS, since the severe course of COVID-19 was thought to develop due to latent MCAS, but the criteria for MCAS in these patients were not reproduced. In the presence of local symptoms, such as urticaria, or in cases of single-organ involvement, e.g., isolated gastrointestinal symptoms, and suspected mast cell activation being basic to pathogenesis, the term mast cell activation disorder was introduced. Moreover, the article discusses several different mediators that are proposed as markers in the diagnosis of MCAS.However, over-diagnosis of MCAS entails the risk of missing the underlying pathology, which is not associated with MCAS, and requires differential diagnosis with a number of diseases. In the absence of severe attacks (with hypotension and shock), the likelihood of MCAS is generally very low. Of course, the patients with mastocytosis and/or confirmed IgE-dependent allergy are at higher risk of developing MCAS, but a key diagnostic marker is an event-related increase in mast cells tryptase from baseline determined over the asymptomatic period. The diagnosis of MCAS is highly likely if the tryptase level rises above a certain threshold (20% of baseline plus 2 ng/mL).
Katiuska H. Liendo-Martínez, Stephany I. Briones-Alvarado, Virginia Gallo-González
et al.
El uso diagnóstico y terapéutico de la broncoscopia flexible (BF) ha tenido una gran evolución desde que Gustav Killian realizó en 1897 la primera endoscopia traqueal para extraer un cuerpo extraño1. Con el pasar de los años se ha demostrado que es un procedimiento seguro2 con una mortalidad escasa (< 0.1%) siendo sus complicaciones infrecuentes y derivadas principalmente del tipo de técnica, de las propias comorbilidades del paciente y de la sedación3. Dentro de las complicaciones infrecuentes podemos mencionar el neumomediastino y el neumoperitoneo que generalmente se deben a la presencia de una ruptura gástrica. Presentamos el caso de un paciente de 58 años que 15 días tras la realización de una BF, presenta el hallazgo incidental de un neumoperitoneo asintomático sin evidencia de lesión gástrica.
Michele Tomasi, Elena Caproni, Mattia Benedet
et al.
A growing body of evidence supports the notion that the gut microbiome plays an important role in cancer immunity. However, the underpinning mechanisms remain to be fully elucidated. One attractive hypothesis envisages that among the T cells elicited by the plethora of microbiome proteins a few exist that incidentally recognize neo-epitopes arising from cancer mutations (“molecular mimicry (MM)” hypothesis). To support MM, the human probiotic Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA-E.coli Nissle) and orally administered to C57BL/6 mice. The treatment with OVA-E.coli Nissle, but not with wild type E. coli Nissle, induced OVA-specific CD8+ T cells and inhibited the growth of tumors in mice challenged with B16F10 melanoma cells expressing OVA. The microbiome shotgun sequencing and the sequencing of TCRs from T cells recovered from both lamina propria and tumors provide evidence that the main mechanism of tumor inhibition is mediated by the elicitation at the intestinal site of cross-reacting T cells, which subsequently reach the tumor environment. Importantly, the administration of Outer Membrane Vesicles (OMVs) from engineered E. coli Nissle, as well as from E. coli BL21(DE3)ΔompA, carrying cancer-specific T cell epitopes also elicited epitope-specific T cells in the intestine and inhibited tumor growth. Overall, our data strengthen the important role of MM in tumor immunity and assign a novel function of OMVs in host-pathogen interaction. Moreover, our results pave the way to the exploitation of probiotics and OMVs engineered with tumor specific-antigens as personalized mucosal cancer vaccines.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Abstract Background Ceftriaxone, a third-generation cephalosporin, is widely used to treat bacterial infections in patients undergoing dialysis because it has a long half-life and broad spectrum of action and does not require dose reduction. However, renal dysfunction is a risk factor for ceftriaxone-associated pseudolithiasis that has rarely been reported in patients undergoing hemodialysis. This study aimed to present the detailed clinical manifestations of, and susceptibility to, ceftriaxone-associated pseudolithiasis in hemodialysis patients. Methods Seventy-seven hemodialysis patients received ceftriaxone between February 2011 and June 2019, and 33 patients underwent abdominal computed tomography within 1 year of receiving the drug. Among these 33 patients, 11 have developed ceftriaxone-associated pseudolithiasis. We retrospectively reviewed these patients’ medical records. We also compared the medical records of ten patients who underwent computed tomography scans within 60 days of ceftriaxone administration and developed ceftriaxone-associated pseudolithiasis with those of patients who did not develop this adverse event. Results Pseudolithiasis tended to develop when patients received ceftriaxone for longer periods or at a higher total dosage. However, the ceftriaxone dose and the disease severity were not significantly correlated. Most patients improved within several months; however, the condition persisted for 10 months in a patient with a spinal cord injury. There were no significant differences in patient characteristics, prevalence of diabetes mellitus or cerebrovascular disease, being bed-bound, fasting, serum albumin, calcium, intact parathormone, or dose per unit body mass between the two groups. However, patients who developed pseudolithiasis had received ceftriaxone for significantly longer and at a higher total dose than those who did not develop pseudolithiasis (12 days; interquartile range [IQ], 8.3–14 vs. 4 days, IQ, 2–8, P = 0.00872; 12.5 g, IQ, 9.3–14 vs. 4 g, IQ, 2–8, P = 0.00476, respectively). Conclusions Ceftriaxone-associated pseudolithiasis may be relatively common in patients undergoing hemodialysis, especially in those who receive a higher total quantity of drug or for a longer duration. It is important to be aware of the possibility of pseudolithiasis developing in hemodialysis patients who receive ceftriaxone. These patients should be monitored during, and for up to 1 year after, its administration.
Harish K. Patel, Jasbir Makker, Ahemd Alemam
et al.
Gastrointestinal symptoms, especially diarrhea, are common with novel coronavirus SARS-CoV-2 infection. Angiotensin-converting enzyme-2 (ACE-2) receptors are heavily expressed in enterocytes and serve as entry receptors for SARS-CoV-2. ACE-2 receptors may also be responsible for pancreatic injury in patients infected with SARS-CoV-2. Diarrhea associated with SARS-CoV-2 is usually believed to be due to viral invasion of enterocytes. However, exocrine pancreatic insufficiency resulting from SARS-CoV-2 is another plausible mechanism leading to diarrhea in such patients. We present a case series of three SARS-CoV-2-infected patients with predominant respiratory symptoms at presentation who developed diarrhea, and further fecal analysis revealed exocrine pancreatic insufficiency as the underlying mechanism.
Diseases of the digestive system. Gastroenterology
Senda Sammoud, Raja Bouguezzi, Yassine Negra
et al.
Background: This study aimed to examine the reliability and sensitivity of a change of direction deficit (CoDD) and to establish its relationship with linear sprint speed. Methods: In total, 89 prepubertal male soccer players participated in this study (age = 11.7 ± 1.2 years, maturity offset = −2.4 ± 1.0). Participants performed the 505 CoD speed test and the 20 m linear sprint speed test with a split interval at 5 m and 10 m. The CoDD was calculated as the mean 505 CoD time—the mean 10 to 20 m time interval. To evaluate the reliability of CoDD, the 505 CoD speed test, and 20 m linear sprint speed were performed twice, one week apart. The sensitivity of CoDD was identified by comparing the values of the typical error of measurement (TEM) and smallest worthwhile change (SWC). Results: Results of the reliability analysis indicated an intraclass correlation coefficient (ICC3.1) < 0.50 (0.47) and a TEM expressed as the coefficient of variation > 5% (10.55%). The sensitivity analysis showed that the ability of the CoDD measure to detect small performance changes is “marginal” (TEM (0.12) > SWC0.2 (0.04)). However, good absolute and relative reliability were observed for the 505 CoD speed test (ICC3.1 = 0.75; TEM < 5%). Alike CoDD, the ability of the 505 CoD speed test to detect small performance changes was rated as “marginal” (TEM (0.07 s) > SWC0.2 (0.04 s)). The CoDD revealed a large association with the 505 CoD speed test (r = 0.71). However, non-significant associations were detected between the CoDD and 5 m, 10 m, and 20 m linear sprint speed intervals (r = 0.10 to 0.16, all <i>p</i> > 0.05). Likewise, non-significant correlations between the 505 CoD speed test and 5 m, 10 m, and 20 m linear sprint speed intervals were observed (r = 0.14 to 0.20, all <i>p</i> > 0.05). Conclusions: The CoDD displayed poor reliability and limited ability to detect small changes in performance in prepubertal male soccer players. Due to its limited practical utility, practitioners are advised not to consider CoDD scores during the assessment of prepubertal male soccer players.
Traumatic neuromas are sometimes formed in the surgical scars. Peripheral nerve injuries lead to complex clinical presentation. They are benign tumors which are formed by critical nerve tissue interaction and are extremely painful. They are formed by intraneural or extraneural scar formation affecting the nerve-gliding plane. Their main clinical presentation is neuropathic pain. This condition is also termed as “painful scar neuropathy.” There have been different approaches to treatment depending on the type of lesion whether it is perineural, endoneurial, or combined and type of pain due to traction or trauma, rest pain, and severity. Varying degrees of therapeutic success has been described in literature using different techniques. There is no consensus on the best therapeutic approach to treat neuropathic pain due to scar tethering. Patient counseling about the condition and the need for multiple interventions, if needed, is essential. Here, we report a case of a 16-year-old female with traumatic neuroma of superficial peroneal nerve formed in the surgical scar of chronic osteomyelitis presenting with severe pain and paresthesia treated by pulsed radio frequency (PRF). PRF is a novel therapeutic method to treat many conditions in pain medicine as it offers treatment without motor deficits and deafferentation syndrome.
Shai Chordekar, Cahtia Adelman, Haim Sohmer
et al.
Context: Damage to the auditory system by loud sounds can be avoided by hearing protection devices (HPDs) such as earmuffs, earplugs, or both for maximum attenuation. However, the attenuation can be limited by air conduction (AC) leakage around the earplugs and earmuffs by the occlusion effect (OE) and by skull vibrations initiating bone conduction (BC). Aims: To assess maximum attenuation by HPDs and possible flanking pathways to the inner ear. Subjects and Methods: AC attenuation and resulting thresholds were assessed using the real ear attenuation at threshold (REAT) procedure on 15 normal-hearing participants in four free-field conditions: (a) unprotected ears, (b) ears covered with earmuffs, (c) ears blocked with deeply inserted customized earplugs, and (d) ears blocked with both earplugs and earmuffs. BC thresholds were assessed with and without earplugs to assess the OE. Results: Addition of earmuffs to earplugs did not cause significantly greater attenuation than earplugs alone, confirming minimal AC leakage through the external meatus and the absence of the OE. Maximum REATs ranged between 40 and 46 dB, leading to thresholds of 46–54 dB HL. Furthermore, calculation of the acoustic impedance mismatch between air and bone predicted at least 60 dB attenuation of BC. Conclusion: Results do not support the notion that skull vibrations (BC) contributed to the limited attenuation provided by traditional HPDs. An alternative explanation, supported by experimental evidence, suggests transmission of sound to inner ear via non-osseous pathways such as skin, soft tissues, and fluid. Because the acoustic impedance mismatch between air and soft tissues is smaller than that between air and bone, air-borne sounds would be transmitted to soft tissues more effectively than to bone, and therefore less attenuation is expected through soft tissue sound conduction. This can contribute to the limited attenuation provided by traditional HPDs. The present study has practical implications for hearing conservation protocols.
Background: Lipid abnormalities, is one of the major causes of cardiovascular diseases in under-dialysis patients. This study aimed to assess the relationship of serum magnesium and blood lipid profile in patients under the peritoneal dialysis and hemodialysis.
Methods: This cross- sectional study was performed on 110 under-dialysis patients in Zahedan, Iran. Serum lipids and magnesium levels were measured. Data were analyzed using t and Pearson correlation tests.
Findings: The mean age of the patients was 46.1 ± 14.7 years. In under-peritoneal dialysis patients, who were not under the treatment of antilipid agents, the correlation of serum magnesium with triglyceride and very low-density lipoprotein cholesterol (VLDL) was significant (P < 0.05); whereas the correlation of serum magnesium with cholesterol and low-density lipoprotein cholesterol (LDL-C) was significant only in subgroup who were under treatment of antilipid agents (P < 0.05). In under-hemodialysis group, the correlation of serum magnesium with cholesterol, triglyceride and was significant (P < 0.05).
Conclusion: This study showed that serum magnesium had correlation with serum lipid profile and could contribute to atherosclerosis and cardiovascular diseases in the patients under the peritoneal dialysis and hemodialysis.