Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course material.These synchronous sessions were co-taught by a group fitness instructor and an anatomy instructor.The fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously covered.After the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental wellbeing.Thirty participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce stress.The majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social connectedness.Overall,medical students saw benefit in PA based interventions to supplement MSK course concepts.Along with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

The influence of resistance exercise training prescription variables on skeletal muscle mass,strength,and physical function in healthy adults:An umbrella review

Purpose:The aim of this umbrella review was to determine the impact of resistance training(RT)and individual RT prescription variables on muscle mass,strength,and physical function in healthy adults.Methods:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,we systematically searched and screened eligible systematic reviews reporting the effects of differing RT prescription variables on muscle mass(or its proxies),strength,and/or physical function in healthy adults aged>18 years.Results:We identified 44 systematic reviews that met our inclusion criteria.The methodological quality of these reviews was assessed using A Measurement Tool to Assess Systematic Reviews;standardized effectiveness statements were generated.We found that RT was consistently a potent stimulus for increasing skeletal muscle mass(4/4 reviews provide some or sufficient evidence),strength(4/6 reviews provided some or sufficient evidence),and physical function(1/1 review provided some evidence).RT load(6/8 reviews provided some or sufficient evidence),weekly frequency(2/4 reviews provided some or sufficient evidence),volume(3/7 reviews provided some or sufficient evidence),and exercise order(1/1 review provided some evidence)impacted RT-induced increases in muscular strength.We discovered that 2/3 reviews provided some or sufficient evidence that RT volume and contraction velocity influenced skeletal muscle mass,while 4/7 reviews provided insufficient evidence in favor of RT load impacting skeletal muscle mass.There was insufficient evidence to conclude that time of day,periodization,inter-set rest,set configuration,set end point,contraction velocity/time under tension,or exercise order(only pertaining to hypertrophy)influenced skeletal muscle adaptations.A paucity of data limited insights into the impact of RT prescription variables on physical function.Conclusion:Overall,RT increased muscle mass,strength,and physical function compared to no exercise.RT intensity(load)and weekly frequency impacted RT-induced increases in muscular strength but not muscle hypertrophy.RT volume(number of sets)influenced muscular strength and hypertrophy.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

2024 Wheelchair Compendium of Physical Activities:An update of activity codes and energy expenditure values

Purpose:This paper presents an update of the 2011 Wheelchair Compendium of Physical Activities designed for wheelchair users and is referred to as the 2024 Wheelchair Compendium.The Wheelchair Compendium aims to curate existing knowledge of the energy expenditure for wheelchair physical activities(PAs).Methods:A systematic review of the published energy expenditure of PA for wheelchair users was completed between 2011 and May 2023.We added these data to the 2011 Wheelchair Compendium data that was compiled previously in a systematic review through 2011.Results:A total of 47 studies were included,and 124 different wheelchair PA reported energy expenditure values ranging from 0.8 metabolic equivalents for wheelchair users(filing papers,light effort)to 11.8 metabolic equivalents for wheelchair users(Nordic sit skiing).Conclusion:In introducing the updated 2024 Wheelchair Compendium,we hope to bridge the resource gap and challenge the prevailing narratives that inadvertently exclude wheelchair users from physical fitness and health PAs.

Speed and surface steepness affect internal tibial loading during running

Background:Internal tibial loading is influenced by modifiable factors with implications for the risk of stress injury.Runners encounter varied surface steepness(gradients)when running outdoors and may adapt their speed according to the gradient.This study aimed to quantify tibial bending moments and stress at the anterior and posterior peripheries when running at different speeds on surfaces of different gradients.Methods:Twenty recreational runners ran on a treadmill at 3 different speeds(2.5 m/s,3.0 m/s,and 3.5 m/s)and gradients(level:0%;uphill:+5%,+10%,and+15%;downhill:-5%,-10%,and-15%).Force and marker data were collected synchronously throughout.Bending moments were estimated at the distal third centroid of the tibia about the medial-lateral axis by ensuring static equilibrium at each 1%of stance.Stress was derived from bending moments at the anterior and posterior peripheries by modeling the tibia as a hollow ellipse.Two-way repeated-measures analysis of variance were conducted using both functional and discrete statistical analyses.Results:There were significant main effects for running speed and gradient on peak bending moments and peak anterior and posterior stress.Higher running speeds resulted in greater tibial loading.Running uphill at+10%and+15%resulted in greater tibial loading than level running.Running downhill at-10%and-15%resulted in reduced tibial loading compared to level running.There was no difference between+5%or-5%and level running.Conclusion:Running at faster speeds and uphill on gradients≥+10%increased internal tibial loading,whereas slower running and downhill running on gradients≥-10%reduced internal loading.Adapting running speed according to the gradient could be a protective mechanism,providing runners with a strategy to minimize the risk of tibial stress injuries.

There is more to the knee joint than just the quadriceps:A systematic review with meta-analysis and evidence gap map of hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders

Background:Impairments in hamstring strength,flexibility,and morphology have been associated with altered knee biomechanics,pain,and function.Determining the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and rehabilitation.This systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders.Methods:Five databases(MEDLINE,Embase,CINAHL,SPORTDiscus,and Web of Science)were searched from inception to September 2022.Only studies comparing hamstring outcomes(e.g.,strength,flexibility,and/or morphology)between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were included.Meta-analyses for each knee disorder were performed.Outcome-level certainty was assessed using the Grading of Recommendations Assessment,Development,and Evaluation,and evidence gap maps were created.Results:Seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofemoral pain(PFP),chondromalacia patellae,and patellar tendinopathy)were included.Individuals with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric(standard mean difference(SMD)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(SMD=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced hamstring strength compared to painfree controls during isometric(SMD=-0.48,95%CI:-0.82 to-0.14),concentric(SMD=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(SMD=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar tendinopathy.Individuals with PFP presented with reduced hamstring flexibility when compared to pain-free controls(SMD=-0.76,95%CI:-1.15 to-0.36).Evidence gap maps identified insufficient evidence for chondromalacia patellae and hamstring morphology across all gradual-onset knee disorders.Conclusion:Our findings suggest that assessing and targeting impairments in hamstring strength and flexibility during rehabilitation may be recommended for individuals with knee OA or PFP.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Older Adult Compendium of Physical Activities:Energy costs of human activities in adults aged 60 and older

Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTDiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older adults.MET values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older adults.Results:We identified 68 articles and extracted energy expenditure data on 427 PAs.From these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older adults.We developed a website to present the OA Compendium MET_(60+)values:https://pacompendium.com.Conclusion:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older adults.It is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.

Public health importance of light intensity physical activity

1.Light intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to achieve health benefits.1-3 Absent from these guidelines are recommendations for light intensity PA(LPA,e.g.,walking at a leisurely pace of 3 km/h or less,equivalent to 1.5-2.9 metabolic equivalents).

Differences between lower extremity joint running kinetics captured by marker-based and markerless systems were speed dependent

Background:The development of computer vision technology has enabled the use of markerless movement tracking for biomechanical analysis.Recent research has reported the feasibility of markerless systems in motion analysis but has yet to fully explore their utility for capturing faster movements,such as running.Applied studies using markerless systems in clinical and sports settings are still lacking.Thus,the present study compared running biomechanics estimated by marker-based and markerless systems.Given running speed not only affects sports performance but is also associated with clinical injury prevention,diagnosis,and rehabilitation,we aimed to investigate the effects of speed on the comparison of estimated lower extremity joint moments and powers between markerless and marker-based technologies during treadmill running as a concurrent validating study.Methods:Kinematic data from marker-based/markerless technologies were collected,along with ground reaction force data,from 16 young adults running on an instrumented treadmill at 3 speeds:2.24 m/s,2.91 m/s,and 3.58 m/s(5.0 miles/h,6.5 miles/h,and 8.0 miles/h).Sagittal plane moments and powers of the hip,knee,and ankle were calculated by inverse dynamic methods.Time series analysis and statistical parametric mapping were used to determine system differences.Results:Compared to the marker-based system,the markerless system estimated increased lower extremity joint kinetics with faster speed during the swing phase in most cases.Conclusion:Despite the promising application of markerless technology in clinical settings,systematic markerless overestimation requires focused attention.Based on segment pose estimations,the centers of mass estimated by markerless technologies were farther away from the relevant distal joint centers,which led to greater joint moments and powers estimates by markerless vs.marker-based systems.The differences were amplified by running speed.

The effectiveness of physical activity interventions on blood pressure in children and adolescents:A systematic review and network meta-analysis

Background:High blood pressure(BP)is a major contributor to mortality and cardiovascular diseases.Despite the known benefits of exercise for reducing BP,it is crucial to identify the most effective physical activity(PA)intervention.This systematic review and network meta-analysis(NMA)aimed to evaluate the available evidence on the effectiveness of various PA interventions for reducing BP and to determine their hierarchy based on their impact on BP.Methods:A search of PubMed,SPORTDiscus,PsycINFO,Web of Science,CINAHL,Cochrane,and Eric databases was conducted up to December 2022 for this systematic review and NMA.Randomized controlled trials and quasi-experimental studies targeting healthy children and adolescents aged 6-12 years old were included in this study.Only studies that compared controlled and intervention groups using PA or exercise as the major influence were included.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines.Three independent investigators performed the literature screening,data extraction,and risk of bias assessment.We used Bayesian arm-based NMA to synthesize the data.The primary outcomes were systolic BP and diastolic BP.We calculated the mean differences(MDs)in systolic BP and diastolic BP before and after treatment.Mean treatment differences were estimated using NMA and random-effect models.Results:We synthesized 27 studies involving 15,220 children and adolescents.PA combined with nutrition and behavior change was the most effective intervention for reducing both systolic BP and diastolic BP(MD=-8.64,95%credible interval(95%CI):-11.44 to-5.84;MD=-6.75,95%CI:-10.44 to-3.11),followed by interventions with multiple components(MD=-1.39,95%CI:-1.94 to-0.84;MD=-2.54,95%CI:-4.89 to-0.29).Conclusion:Our findings suggest that PA interventions incorporating nutrition and behavior change,followed by interventions with multiple components,are most effective for reducing both systolic BP and diastolic BP in children and adolescents.

The Paris 2024 Olympic and Paralympic Games

The first modern Olympic Games took place in Athens in 1896.While in those early days of the Olympics only amateur and gentleman athletes were allowed to participate,today Olympic athletes are highly trained professionals often dedicating decades of preparation for the chance to compete in the Olympic Games.In sharp contrast to these highly trained athletes,the world’s population becomes less physically active on average,resulting in an obesity epidemic with associated metabolic syndrome and increased mortality through non-communicable diseases(e.g.,Collins et al.^(1)).

Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients

Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and survival.Preventing and managing breast cancer-related symptoms soon after diagnosis is essential.The purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer patients.Methods:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis.HRF measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body composition.Symptom measures included depression,sleep quality,and fatigue.Adjusted multivariable logistic regression was performed for analyses.Results:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate depression.In multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(p<0.001),poor sleep quality(p=0.009),significant fatigue(p=0.008),any symptom(p<0.001),and multiple symptoms(p<0.001).VO_(2peak)demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile.The strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple symptoms.Moreover,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients.Other HRF parameters may also be important for specific symptoms.Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes.

The emerging role of exercise as a cancer treatment

Over the past few decades,exercise oncology has emerged as an important subfield within exercise science.Over that time,substantial progress has been made in understanding the role of exercise in people newly diagnosed with cancer,actively being treated for cancer,and recovering after cancer treatments.

Commentary on “Why people should run after positive affective experiences instead of health benefits”

Maltagliati et al.1 recently highlighted the vital role of affective experiences in promoting physical activity(PA).The authors suggested that positive affective experiences,rather than health benefits,can tip the balance in favor of PA over sedentary alternatives.The authors proposed a new formal decision model between PA and sedentary alternatives and reported that when health benefits are the unique reason to action,the costs of PA(e.g.,effort)and the subjective value(SV)of sedentary alternatives(V_(sed))are the main drivers of decision-making processes.

A scoping review of methodologies for applying artificial intelligence to physical activity interventions

Purpose This scoping review aimed to offer researchers and practitioners an understanding of artificial intelligence(AI)applications in physical activity(PA)interventions;introduce them to prevalent machine learning(ML),deep learning(DL),and reinforcement learning(RL)algorithms;and encourage the adoption of AI methodologies.Methods A scoping review was performed in PubMed,Web of Science,Cochrane Library,and EBSCO focusing on AI applications for promoting PA or predicting related behavioral or health outcomes.AI methodologies were summarized and categorized to identify synergies,patterns,and trends informing future research.Additionally,a concise primer on predominant AI methodologies within the realm of PA was provided to bolster understanding and broader application.Results The review included 24 studies that met the predetermined eligibility criteria.AI models were found effective in detecting significant patterns of PA behavior and associations between specific factors and intervention outcomes.Most studies comparing AI models to traditional statistical approaches reported higher prediction accuracy for AI models on test data.Comparisons of different AI models yielded mixed results,likely due to model performance being highly dependent on the dataset and task.An increasing trend of adopting state-of-the-art DL and RL models over standard ML was observed,addressing complex human–machine communication,behavior modification,and decision-making tasks.Six key areas for future AI adoption in PA interventions emerged:personalized PA interventions,real-time monitoring and adaptation,integration of multimodal data sources,evaluation of intervention effectiveness,expanding access to PA interventions,and predicting and preventing injuries.Conclusion The scoping review highlights the potential of AI methodologies for advancing PA interventions.As the field progresses,staying informed and exploring emerging AI-driven strategies is essential for achieving significant improvements in PA interventions and fostering overall well-being.

Commentary on"Speed and surface steepness affect internal tibial loading during running"

It is a pleasure to write a commentary on the work of Dr.Hannah Rice and colleagues,l who have advanced our understanding of how the mechanical loading environment of the tibia changes as a function of running grade and speed.It is important that we understand how the tibia is loaded during conditions that an individual is likely to encounter when running as it is these internal loads which we believe are responsible for the development of bone-stress injuries.

Primary hyperparathyroidism-induced acute pancreatitis in pregnancy:A systematic review with a diagnostic-treatment algorithm

BACKGROUND Primary hyperparathyroidism(PHPT)-induced acute pancreatitis(AP)during pregnancy has rarely been described.Due to this rarity,there are no diagnostic or treatment algorithms for pregnant patients.AIM To determine appropriate diagnostic methods,therapeutic options,and factors related to maternal and fetal outcomes for PHPT-induced AP in pregnancy.METHODS A literature search of articles in English,Japanese,German,Spanish,and Italian was performed using PubMed(1946-2023),PubMed Central(1900-2023),and Google Scholar.The Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)protocol was followed.The search terms included“pancreatite acuta,”“iperparatiroidismo primario,”“gravidanza,”“travaglio,”“puerperio,”“postpartum,”“akute pankreatitis,”“primärer hyperparathyreoidismus,”“Schwangerschaft,”“Wehen,”“Wochenbett,”“pancreatitis aguda,”“hiperparatiroidismo primario,”“embarazo,”“parto,”“puerperio,”“posparto,”“acute pancreatitis,”“primary hyperparathyroidism,”“pregnancy,”“labor,”“puerperium,”and“postpartum.”Additional studies were identified by reviewing the reference lists of retrieved studies.Demographic,imaging,surgical,obstetric,and outcome data were obtained.RESULTS Fifty-four cases were collected from the 51 studies.The median maternal age was 29 years.PHPT-induced AP starts at the 20th gestational week;higher gestational weeks were seen in mothers who died(mean gestational week 28).Median values of amylase(1399,Q1-Q3=519-2072),lipase(2072,Q1-Q3=893-2804),serum calcium(3.5,Q1-Q3=3.1-3.9),and parathormone(PTH)(384,Q1-Q3=123-910)were reported.In 46 cases,adenoma was the cause of PHPT,followed by 2 cases of carcinoma and 1 case of hyperplasia.In the remaining 5 cases,the diagnosis was not reported.Neck ultrasound was positive in 34 cases,whereas sestamibi was performed in 3 cases,and neck computed tomography or magnetic resonance imaging was performed in 9 cases(the enlarged parathyroid gland was not localized in 3 cases).Surgery was the preferred treatment during pregnancy in 33 cases(median week of gestation 25,Q1-Q3=20-30)and postpartum in 12 cases.The timing was not reported in the remaining 9 cases,or surgery was not performed.AP was managed surgically in 11 cases and conservatively in 43(79.6%)cases.Maternal and fetal mortality was 9.3%(5 cases).Surgery was more common in deceased mothers(60.0%vs 16.3%;P=0.052),and PTH values tended to be higher in this group(910 pg/mL vs 302 pg/mL;P=0.059).Maternal mortality was higher with higher serum lipase levels and earlier delivery week.Higher calcium(4.1 mmol/L vs 3.3 mmol/L;P=0.009)and PTH(1914 pg/mL vs 302 pg/mL;P=0.003)values increased fetal/child mortality,as well as abortions(40.0%vs 0.0%;P=0.007)and complex deliveries(60.0%vs 8.2%;P=0.01).CONCLUSION If serum calcium is not tested during admission,definitive diagnosis of PHPT-induced AP in pregnancy is delayed,while early diagnosis and immediate intervention lead to excellent maternal and fetal outcomes.

Managing end-stage carcinoid heart disease:A case report and literature review

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of life.Cardiovascular complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic disease.CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases.During the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to follow-up.After 10 years,he presented to the emergency room with signs and symptoms of right-sided heart failure.Panneuroendocrine markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic metastases.Computed tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis.Furthermore,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart disease.The patient was not a candidate for valve replacement.He started octreotide acetate treatment,and the dose escalated to 80 mg IM monthly.Although biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart failure.Carcinoid heart disease and tumor burden are major prognostic factors of poor survival.Therefore,they must be actively sought by available biochemical markers and imaging techniques.Moreover,imaging techniques aiding tumor detection and staging,somatostatin receptor positron emission tomography/CT,and CT or magnetic resonance imaging,should be performed at the time of diagnosis and in 3-to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery.Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered,while any delay can worsen right-sided ventricular failure.