Female breast cancer survivors who underwent unilateral breast cancer surgery ( total or conservative) and completed their adjuvant therapies such as chemotherapy and radiotherapy prior to participation in this study.

Breast Cancer

Breast Cancer Female

Breast Cancer Lymphedema

Breast Carcinoma in Situ

Hand Grasp

Pain, Shoulder

Being a woman and having the right or left unilateral breast cancer surgery

Sub-tissue fluid proportion will be evaluated via Moisture Meter D (Delfin Technologies, Kuopio, Finland) on both upper extremity (right and left) in predefined reference points on volar side (6 cm distal and 8 cm proximal points from cubital crease, 10 cm inferior side point from axilla and dorsal point of web space in the hand) by using four different probes which can assess 0.5 mm, 1.5 mm, 2.5 mm and 5.0 mm depth. Values taken by 2.5 mm depth probe will be used to calculate the ratio (affected side TDC value/Unaffected side TDC value) to stage lymphedema severity along with the International Society of Lymphology staging system. This device mainly aims to assess the dielectric constant of tissues which is related to the amount of tissue water. In the case of pre-lymphedema or lymphedema, one can assess objectively regarding sub-tissue fluid changes via this device. Triplicate measurements will be taken for each reference point.

Tissue Dielectric Constant Measurement

Participants' muscle strength of shoulder flexion, abduction, and elbow flexion will be assessed via Handheld digital dynamometer (Lafayette Manual Muscle Tester, Model 01165, LaFayette Instruments, NY, USA). Both upper extremities will be assessed three times and the average value will be recorded.

Muscle strength measurement

Handgrip strength will be assessed with LaFayette Professional Hand Dynamometer, Model 5030L1, LaFayette Instruments, NY, USA). The standard position which can be achieved by 90-degree elbow flexion, shoulder abducted, and hand mid-prone positioned; 90-degree shoulder abduction and 90-degree shoulder abduction positions will be used to assess hang-grip strength. Three measurements will be requested and the maximum value of them will be recorded. 1 minute resting period will be provided between the positions at which handgrip is assessed.

Hand-Grip Strength Measurement

The sensitive pain threshold and normal pain threshold will be evaluated by a digital algometer (Wagner FDIX, Greenwich, USA) on reference points as follows: C5-C6 zygapophyseal joints' lateral points, upper trapezius (proximal, middle and distal lateral points, length measured by a tape from C7 Processus spinosus to acromion and this length will be divided equally into three parts for proximal, middle and distal lateral point), deltoid muscle (crista deltoidea), dorsum of the webspace.

Pain Threshold Measurement

This scale was intended to be filled to assess participants' physical activity levels within the last seven days. Then, MET calculations will be done via a basic Excel Spreadsheet which is pre-defined MET values formulated inside. Scale data then obtained according to the participants' answers and recorded.

International Physical Activity Questionnaire-Short Form (IPAQ-SF)

This scale has 9 items that can be answered as "Strongly Disagree" through "Strongly Agree" by numbered as 1 and 7, respectively. Then total points will be calculated and divided into 9 to achieve the Fatigue Impact Scale score. The higher points will be indicated more perceived fatigue, while lower points indicate less.

Fatigue Impact Scale

DASH has 30 items related to upper extremity function. Participants will be requested to grade some expressions related to the function within a 5-point Likert scale as follows: "No difficulty: 1, Mild Difficulty:2, Moderate Difficulty: 3, Severe Difficulty: 4 and Unable to perform: 5). The symptom score of the DASH will be calculated as dividing filled items total score to filled items' number and minus one from this data then multiplying with 25. The higher points indicate a deteriorated shoulder and hand function while lower points indicate a better upper extremity function.

Disabilities of Arm, Shoulder and Hand Scale (DASH)

Exercise Benefits/Barriers Scale has 43 items each can be graded within a four-point Likert type scale. Barrier items are reverse coded. 43 items are all related to exercise and exercise beliefs in both in the aspect of health and general. Strongly disagree, disagree, agree, strongly agree will be scored as 1,2,3,4 or vice versa whether the item should de reversely coded, respectively. Total scores ranged between 29 and 172. The barrier scale score is ranged between 14 and 56. The benefits scale is also ranged between 29 and 116. The higher the score of Barriers scale, the greater the perception of barriers to exercise.

Exercise Benefits/ Barriers Scale

Beck Depression Scale has 21 items each can be scored within 0 to 3. All items are related to the depressive mood of a participant. The higher the score of the Beck Depression Scale, the higher the depression level.

Beck Depression Scale

İzmir Çiğli State Training Hospital

Factors Affecting Functionality in Breast Cancer Survivors

Investigation of the Factors of Hang-Grip Strength-related Upper Extremity Functionality After Breast Cancer Surgery

Sub-tissue fluid proportion will be evaluated via Moisture Meter D (Delfin Technologies, Kuopio, Finland) on both upper extremity (right and left) in predefined reference points on volar side (6 cm distal and 8 cm proximal points from cubital crease, 10 cm inferior side point from axilla and dorsal point of web space in the hand) by using four different probes which can assess 0.5 mm, 1.5 mm, 2.5 mm and 5.0 mm depth. Values taken by 2.5 mm depth probe will be used to calculate the ratio (affected side TDC value/Unaffected side TDC value) to stage lymphedema severity along with the International Society of Lymphology staging system.

Participants' muscle strength of shoulder flexion, abduction, and elbow flexion will be assessed via Handheld digital dynamometer (Lafayette Manual Muscle Tester, Model 01165, LaFayette Instruments, NY, USA). Both upper extremities will be assessed three times and the average value will be recorded. 1 minute resting period will be provided between the positions at which muscle strength is assessed.

The sensitive pain threshold and normal pain threshold will be evaluated by a digital algometer (Wagner FDIX, Greenwich, USA) on reference points as follows: C5-C6 zygapophyseal joints' lateral points, upper trapezius (proximal, middle and distal lateral points, length measured by a tape from C7 Processus spinosus to acromion and this length will be divided equally into three parts for proximal, middle and distal lateral point), deltoid muscle (crista deltoidea), dorsum of the webspace. Measurements will te took both for right and left upper extremity. Units will be recorded as kgf.

Alper Tuğral

Alper Tuğral, PT, MSc, Lecturer. Izmir Bakircay University Faculty of Health Sciences, Department of Physical Therapy and Rehabilitation

Izmir Bakircay University

The study period is from the start of study treatment, cycle 1 day 1 until 28 days after the last treatment dose. (Cycle 5 day 9). Treatment will be continued until cycle 5 is completed or the study is terminated for the patient. The cycles will be repeated every 28 days. Cycle 1 Day 1 of study treatment will be between day +30 and day +45 post-transplant. Each 28-day cycle is comprised of Pevonedistat at 20 mg/m2 IV infusion over 1 hour on days 1, 3 and 5 and Azacitidine at 25 mg/m2 IV infusion over 30 minutes on days 1, 2, 3, 4, 5, 8 and 9. The drugs can be administered either through a central catheter or a peripheral line.

Acute Myeloid Leukemia (AML)

To assess the toxicity and efficacy of a combination of Pevonedistat and Azacitidine as post allogeneic hematopoietic stem cell transplant maintenance therapy for non-remission AML.

Pevonedistat

Although hematopoietic stem cell transplantation (HSCT) is curative for many patients with AML, AML in relapse at the time of transplant is still a major challenge with low rates of leukemia-free survival even with an intensive myeloablative conditioning.

transplant

Azacitidine

Penn State Hershey Medical Center: Penn State Cancer Institute

Pevonedistat and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission AML

A Phase II Study of Pevonedistat (MLN4924, TAK924) and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission Acute Myelogenous Leukemia

Cumulative incidence of relapse at 2 years

Shin Mineishi

Professor and Director, Blood and Marrow Transplant Program

Milton S. Hershey Medical Center

Millennium Pharmaceuticals, Inc.

Takeda

A humidified mixture of gas will be delivered by mask, nasal cannulae, and small room-sized tent. Inspiratory oxygen fraction (FiO2) will be gradually decreased to 11% over a period or five days to obtain a peripheral capillary O2 saturation (SpO2) between 80%-85% (corresponding to 40-55 mmHg of arterial partial oxygen pressure (PaO2)). Healthy volunteers will be monitored and blood and urine will be obtained at 24h and 48 hours after returning to normoxia.

Healthy Volunteers

To create the correct gas mixture, nitrogen tanks or membrane technology nitrogen generators will be utilized.
Humidified, high flow, hypoxic gas by nasal cannula will allow the participant to walk short distances, eat, execute basic personal needs (e.g., use of toilette, washing, bathing etc.), or take breaks from wearing the mask.

Inhaled Nitrogen

Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation.

Hypoxia as a therapy for mitochondrial disease.

Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial.

Massachusetts General Hospital

Prolonged Hypoxic Breathing in Healthy Volunteers: a Safety Study

Physiological and Biochemical Response to Prolonged Exposure to Hypoxic Breathing in Healthy Volunteers

Peripheral oxygen saturation of the healthy volunteers receiving different levels of FiO2 will be continuously monitored for the 5 days of hypoxia titration and the 2 days after return to normoxia.

Erythropoietin will be tested each day during the 7 day study period.

Pulmonary pressure will be non-invasively measured via transthoracic echocardiography each day during the 7 day study period.

Plasma reactive oxygen species (ROS) will be evaluated each day during the 7 day study period.

Venous acid-base status will be evaluated each day during the 7 day study period.

Systemic blood pressure will be regularly monitored during the 7 day study period.

Heart rate will be continuously monitored via electrocardiography (EKG) during the 7 day study period.

Respiratory rate will be regularly monitored during the 7 day study period.

Lactate levels will be tested each day during the 7 day study period.

Alpha-hydroxybutyrate levels will be tested each day during the 7 day study period.

Lorenzo Berra, MD

Assistant Professor of Anesthesia

Rezoagli, Emanuele, M.D., Massachusetts General Hospital, Harvard Medical School

Ferrari, Michele, M.D., Massachusetts General Hospital, Harvard Medical School

Patel, Sarvagna, B.A., Massachusetts General Hospital, Harvard Medical School

Zapol, Warren M., M.D., Massachusetts General Hospital, Harvard Medical School

Fisher, Daniel, R.R.T., Massachusetts General Hospital, Harvard Medical School

Jain, Isha, B.A., Massachusetts General Hospital, Harvard Medical School

Mootha, Vamsi, M.D., Massachusetts General Hospital, Harvard Medical School

Harris, Stuart N., M.D., Massachusetts General Hospital, Harvard Medical School

Karaa, Amel, M.D., Massachusetts General Hospital, Harvard Medical School

Iron Overload

All patients will receive monthly phlebotomies.

cellulitis/fatigue

Factors Affecting Functionality in Breast Cancer Survivors

Pevonedistat and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission AML

Prolonged Hypoxic Breathing in Healthy Volunteers: a Safety Study

Safety and Efficacy of Iron Reduction by Phlebotomy

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